ORCID Profile
0000-0001-9053-7976
Current Organisation
University of Parma
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: MDPI AG
Date: 10-05-2019
DOI: 10.3390/JCM8050655
Abstract: The electrical stability of the myocardium is dependent on the dynamic balance between sympathetic and parasympathetic influences on the heart, which is reflected by heart rate variability (HRV). Reduced HRV is a proposed predictor of sudden death caused by ventricular tachyarrhythmias in cardiac patients. However, the link between in idual differences in HRV and ventricular tachyarrhythmic risk in populations without known pre-existing cardiac conditions is less well explored. In this study we investigated the extent to which in idual differences in resting state HRV predict susceptibility to spontaneous and pharmacologically-induced ventricular arrhythmias in healthy rats. Radiotelemetric transmitters were implanted in 42 adult male Wild-type Groningen rats. ECG signals were recorded during 24-h resting conditions and under β-adrenoceptor pharmacological stimulation with isoproterenol and analyzed by means of time- and frequency-domain indexes of HRV. No significant association was found between in idual differences in resting measures of HRV and spontaneous incidence of ventricular arrhythmias. However, lower resting values of HRV predicted a higher number of ventricular ectopic beats following β-adrenergic pharmacological stimulation with isoproterenol (0.02 mg/kg). Moreover, after isoproterenol administration, one rat with low resting HRV developed sustained ventricular tachycardia that led to death. The present results might be indicative of the potential utility of HRV measures of resting cardiac autonomic function for the prediction of ventricular arrhythmias, particularly during conditions of strong sympathetic activation, in populations without known cardiac disease.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Oxford University Press (OUP)
Date: 12-2020
DOI: 10.1093/ABM/KAAA094
Abstract: African Americans have the highest rates of hypertension-related disease of any ethnic group in the USA. Importantly, racism and discrimination have been linked to these higher rates of morbidity and mortality. Discrimination is deleterious not only to those that are the recipients of this unfair treatment but also to the partners and family members of those affected as well to those that perpetrate this bias. In this paper, we identify a unique pattern of physiological response to unfair treatment, we have called the “cardiovascular conundrum.” This pattern is characterized by greater heart rate variability and greater total peripheral resistance in African Americans compared to their European American counterparts. We review the evidence supporting the existence of this pattern and propose several physiological and psychological factors that might underpin it. We also propose a number of factors that might help to mitigate the deleterious effects associated with it. Whereas the context of the current review is on Black/White disparities the framework we propose may be relevant to others exposed to unfair treatment. Ultimately, the systemic factors that perpetuate these inequalities will require that we first acknowledge and then face the challenges they present if we are to address the wealth and health disparities in our country.
Publisher: Wiley
Date: 10-10-2020
DOI: 10.1111/PSYP.13688
Abstract: Understanding the association between autonomic nervous system [ANS] function and brain morphology across the lifespan provides important insights into neurovisceral mechanisms underlying health and disease. Resting‐state ANS activity, indexed by measures of heart rate [HR] and its variability [HRV] has been associated with brain morphology, particularly cortical thickness [CT]. While findings have been mixed regarding the anatomical distribution and direction of the associations, these inconsistencies may be due to sex and age differences in HR/HRV and CT. Previous studies have been limited by small s le sizes, which impede the assessment of sex differences and aging effects on the association between ANS function and CT. To overcome these limitations, 20 groups worldwide contributed data collected under similar protocols of CT assessment and HR/HRV recording to be pooled in a mega‐analysis ( N = 1,218 (50.5% female), mean age 36.7 years (range: 12–87)). Findings suggest a decline in HRV as well as CT with increasing age. CT, particularly in the orbitofrontal cortex, explained additional variance in HRV, beyond the effects of aging. This pattern of results may suggest that the decline in HRV with increasing age is related to a decline in orbitofrontal CT. These effects were independent of sex and specific to HRV with no significant association between CT and HR. Greater CT across the adult lifespan may be vital for the maintenance of healthy cardiac regulation via the ANS—or greater cardiac vagal activity as indirectly reflected in HRV may slow brain atrophy. Findings reveal an important association between CT and cardiac parasympathetic activity with implications for healthy aging and longevity that should be studied further in longitudinal research.
Publisher: Elsevier BV
Date: 02-2021
DOI: 10.1016/J.PSYNEUEN.2020.105070
Abstract: The left dorsolateral prefrontal cortex (dlPFC) has been implicated in the regulation of stress-related cognitive processes and physiological responses and is the principal target of noninvasive brain stimulation techniques applied to psychiatric conditions. However, existing studies are mostly correlational and causal evidence on the role of this region in mediating specific psychophysiological mechanisms underpinning stress-related responses are needed to make the application of such techniques more efficient. To fill this gap, this study used inhibitory continuous theta burst stimulation (cTBS) in healthy in iduals to examine the extent to which activity of the left dlPFC is associated with cognitive (subjective focus on a tracking task), behavioral (reaction times and variability), and physiological responses (heart rate and its variability and cortisol level) following induction of perseverative cognition. Compared to sham and left ventral PreMotor area stimulation (as active control area), inhibition of left dlPFC determined sustained autonomic and neuroendocrine activation and increased the subjective perception of being task-focused, while not changing the behavioral and self-reported stress-related responses. Adopting a causative approach, we describe a role of left dlPFC in inhibitory control of the physiological stress-response associated to perseverative thinking.
Publisher: PAGEPress Publications
Date: 10-01-2014
Abstract: Previously, we observed that a single low-intensity premature ventricular stimulation could occasionally induce spontaneous ectopic beats in normal rat hearts. Possible hypothesis for the arrhythmia is that a premature beat can encounter a zone of conduction block to initiate reentry. However, enhanced dispersion of repolarization, a necessary condition for initiation of reentry, is unlikely to be present in normal myocardium. Thus, the main objective of the present study was to perform detailed pace mapping measurements in normal ventricular myocardium with a view to identify pacing sites and critical coupling intervals which could induce spontaneous ectopic beats and to characterize the reentrant circuits.
Publisher: Springer Science and Business Media LLC
Date: 14-12-2015
DOI: 10.1038/SREP18218
Abstract: In humans, chronic anxiety represents an independent risk factor for cardiac arrhythmias and sudden death. Here we evaluate in male Wistar rats bred for high (HAB) and low (LAB) anxiety-related behavior, as well as non-selected (NAB) animals, the relationship between trait anxiety and cardiac electrical instability and investigate whether pharmacological augmentation of endocannabinoid anandamide-mediated signaling exerts anxiolytic-like and cardioprotective effects. HAB rats displayed (i) a higher incidence of ventricular tachyarrhythmias induced by isoproterenol and (ii) a larger spatial dispersion of ventricular refractoriness assessed by means of an epicardial mapping protocol. In HAB rats, acute pharmacological inhibition of the anandamide-degrading enzyme, fatty acid amide hydrolase (FAAH), with URB694 (0.3 mg/kg), (i) decreased anxiety-like behavior in the elevated plus maze, (ii) increased anandamide levels in the heart, (iii) reduced isoproterenol-induced occurrence of ventricular tachyarrhythmias and (iv) corrected alterations of ventricular refractoriness. The anti-arrhythmic effect of URB694 was prevented by pharmacological blockade of the cannabinoid type 1 (CB 1 ), but not of the CB 2 , receptor. These findings suggest that URB694 exerts anxiolytic-like and cardioprotective effects in HAB rats, the latter via anandamide-mediated activation of CB 1 receptors. Thus, pharmacological inhibition of FAAH might be a viable pharmacological strategy for the treatment of anxiety-related cardiac dysfunction.
Publisher: MDPI AG
Date: 27-08-2019
DOI: 10.3390/MICROORGANISMS7090293
Abstract: Bifidobacteria commonly constitute the most abundant group of microorganisms in the healthy infant gut. Their intestinal establishment is believed to be maternally driven, and their acquisition has even been postulated to occur during pregnancy. In the current study, we evaluated bifidobacterial mother-to infant transmission events in a rat model by means of quantitative PCR (qPCR), as well as by Internally Transcribed Spacer (ITS) bifidobacterial profiling. The occurrence of strains supplied by mothers during pregnancy to their corresponding newborns was observed and identified by analysis immediately following C-section delivery. These findings provide intriguing support for the existence of an unknown route to facilitate bifidobacterial transfer during the very early stages of life.
Publisher: Public Library of Science (PLoS)
Date: 14-11-2014
Publisher: Springer Singapore
Date: 2016
Publisher: Elsevier BV
Date: 05-2021
Publisher: Elsevier BV
Date: 2023
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.BBI.2019.04.007
Abstract: Sleep is altered in response to an immune challenge: non-rapid eye movement (NREM) sleep is increased and fragmented, REM sleep is inhibited. Sleep and immune response are affected by stress: several stressors inhibit sleep and increase waking time stress-induced cortisol secretion affects the immune response, with immunosuppressive effects. Different levels of trait aggressiveness are associated with specific patterns of neuroendocrine and autonomic stress responsiveness. Aim of this study was to test the hypothesis that trait aggressiveness, by affecting response to stressors, modifies sleep alterations induced by the activation of the immune response. To this aim, rats were selected on the basis of their latency time to attack a male intruder in the resident-intruder test. Animals were instrumented for chronic recordings of sleep-wake activity and injected, intraperitoneally, with an immune challenge (250 μg/kg lipopolysaccharide - LPS, a component of gram-negative bacterial cell wall). Here we report that high aggressive (HA) rats responded to an immune challenge with a 24-h long increase in cortical brain temperature. During the first 12 post-injection hours, HA rats also responded with a prolonged increase in NREM sleep amount, and a 5-h long and continuous inhibition of REM sleep. In HA rats, the LPS-induced increase in the amount of time spent in NREM sleep was due to an increase in the number of episodes of this sleep phase, without any change in the bout duration. The LPS-induced REM sleep inhibition observed in HA rats was due to a decrease in both the number and duration of REM sleep bouts. In HA rats, during REM sleep, LPS administration significantly reduced the power of the EEG theta band. In non-aggressive (NA) rats, in response to LPS administration, cortical brain temperature was increased only for two hours, NREM sleep was unaffected, and REM sleep inhibition was scattered along the first 8 post-injection hours. The LPS-induced changes in the number of NREM sleep bouts of NA rats were limited to few and scattered hours, with a change in bout duration only in a single hour. A combination of decreases, in few hours, in both REM sleep bouts and their duration contributed to the REM sleep inhibition observed in NA rats. In NA rats, the power of EEG theta band was not modified, during REM sleep, by LPS administration. Gross motor activity was inhibited in both HA and NA rats. Results of this study show that trait aggressiveness affects febrile and sleep responses to an immune challenge.
Publisher: Frontiers Media SA
Date: 24-03-2014
Publisher: Informa UK Limited
Date: 10-04-2021
Publisher: Elsevier BV
Date: 02-2014
DOI: 10.1016/J.NEUBIOREV.2013.12.005
Abstract: The existence of a close relationship between psychosocial factors and cardiovascular morbidity is not just a hypothesis anymore. Research on humans has been attempting to unravel the significance of this association by investigating psychological and social characteristics in relation to cardiovascular health. However, this research is limited by the difficulty to control and standardize for the in idual social history, the impossibility to apply psychosocial stress stimuli for mere experimental purposes, as well as the long time span of cardiovascular pathogenesis in humans. Animal studies controlling for social environment and adverse social episodes since weaning allow for partially overcoming these limitations. The aim of this review is to provide an up-to-date reference of the experimental evidence so far collected on the link between psychosocial factors and cardiovascular (dys-)function in rodent species, with special emphasis on social conflict, aggressiveness and negative mood states, which have been significantly associated with increased risk of cardiovascular disease.
Publisher: Informa UK Limited
Date: 04-05-2015
DOI: 10.3109/10253890.2015.1045868
Abstract: Depression occurs in people of all ages across all world regions it is the second leading cause of disability and its global burden increased by 37.5% between 1990 and 2010. Autonomic changes are often found in altered mood states and appear to be a central biological substrate linking depression to a number of physical dysfunctions. Alterations of autonomic nervous system functioning that promotes vagal withdrawal are reflected in reductions of heart rate variability (HRV) indexes. Reduced HRV characterizes emotional dysregulation, decreased psychological flexibility and defective social engagement, which in turn are linked to prefrontal cortex hypoactivity. Altogether, these pieces of evidence support the idea that HRV might represent a useful endophenotype for psychological hysical comorbidities, and its routine application should be advised to assess the efficacy of prevention/intervention therapies in a number of psychosomatic and psychiatric dysfunctions. Further research, also making use of appropriate animal models, could provide a significant support to this point of view and possibly help to identify appropriate antidepressant therapies that do not interefere with physical health.
Publisher: Public Library of Science (PLoS)
Date: 17-05-2013
Publisher: Springer Science and Business Media LLC
Date: 21-02-2023
DOI: 10.1186/S13030-023-00266-5
Abstract: Surgeons are exposed to high levels of intraoperative stress, which could compromise their psychological well-being in the long term. This study aimed at exploring the effects of real operations on the activity of stress response systems (i.e., cardiac autonomic function and hypothalamic–pituitary–adrenal axis) during and in the aftermath of surgery, and the moderating role of in idual psychobiological characteristics and different levels of experience (senior vs expert surgeons). Heart rate, heart rate variability, and salivary cortisol measures (as indexes of cardiac autonomic and hypothalamic–pituitary–adrenal axis activity, respectively) were assessed during real operations and in the perioperative period in a s le of surgeons ( n = 16). Surgeons’ psychometric characteristics were collected using questionnaires. Results. Real operations triggered both cardiac autonomic and cortisol stress responses which were independent from surgeons’ level of experience. Intraoperative stress responses did not affect cardiac autonomic activity during the following night but were associated with a blunted cortisol awakening response. Moreover, senior surgeons reported higher levels of negative affectivity and depressive symptoms than expert surgeons prior to the surgery. Lastly, the magnitude of heart rate responses to surgery positively correlated with scores on negative affectivity, depression, perceived stress, and trait anxiety scales. This exploratory study allows to put forward the hypotheses that in surgeons cardiac autonomic and cortisol stress responses to real operations (i) may be associated with specific in idual psychological characteristics regardless of the level of experience, (ii) and may have a longer lasting impact on hypothalamic–pituitary–adrenal axis function with potential implications for surgeons’ physical and psychological well-being.
Publisher: Elsevier BV
Date: 05-2017
DOI: 10.1016/J.NEUBIOREV.2016.11.006
Abstract: Numerous epidemiological studies have demonstrated a close and bidirectional association between depression and cardiovascular disorders (CVD). This comorbidity places a significant burden on in iduals and the healthcare system. Not surprisingly, in the last two decades preclinical research in the field of depression and CVD has rapidly progressed. Multiple studies have demonstrated that aspects of human depression/cardiovascular comorbidity can be modeled in rodents exposed to chronic stress paradigms and that a depressive-like syndrome can be induced in rodent models of CVD. This research has provided insights into neural, autonomic, humoral, immune and circulatory mechanisms linking co-occurring mood and CVD. Recent investigations have started to address gender and in idual differences in the vulnerability to both disorders and have begun to explore the efficacy of novel pharmacological interventions for the treatment of these comorbid conditions. This review discusses relatively well-established findings and the latest discoveries from rodent models of depression and CVD, with the aim of providing an up-to-date reference which may guide future studies of the relationship between mood and cardiovascular disturbances.
Publisher: Informa UK Limited
Date: 08-06-2020
DOI: 10.1080/10253890.2019.1625884
Abstract: Prolonged or repeated activation of the stress response can have negative psychological and physical consequences. The prefrontal cortex (PFC) is thought to exert an inhibitory influence on the activity of autonomic and neuroendocrine stress response systems. In this study, we further investigated this hypothesis by increasing PFC excitability using transcranial direct current stimulation (tDCS). Healthy male participants were randomized to receive either anodal (excitatory) tDCS (
Publisher: Elsevier BV
Date: 12-2014
DOI: 10.1016/J.RESP.2014.07.003
Abstract: Respiratory patterns represent a promising physiological index for assessing emotional states in preclinical studies. Since disturbed emotional regulation may lead to forms of excessive aggressiveness, in this study we investigated the hypothesis that rats that differ largely in their level of aggressive behavior display matching alterations in respiration. Respiration was recorded in male high-aggressive (HA, n = 8) and non-aggressive (NA, n = 8) Wild-type Groningen rats using whole-body plethysmography. Subsequently, anxiety-related behaviors were evaluated in the elevated plus maze and social avoidance-approach tests. During respiratory testing, HA rats showed elevated basal respiratory rate, reduced sniffing, exaggerated tachypnoeic response to an acoustic stimulus and a larger incidence of sighs. In addition, HA rats spent less time in the open arms of the plus maze and displayed higher levels of social avoidance behavior compared to NA rats. These findings indicate that HA rats are characterized by alterations in respiratory functioning and behavior that are overall indicative of an anxiety-like phenotype.
Publisher: Springer Science and Business Media LLC
Date: 24-08-2020
DOI: 10.1038/S41598-020-70986-Z
Abstract: Gamma aminobutyric acid (GABA) is the principal inhibitory neurotransmitter playing a key role in anxiety and depression disorders in mammals. Recent studies revealed that members of the gut microbiota are able to produce GABA modulating the gut–brain axis response. Among members of the human gut microbiota, bifidobacteria are well known to establish many metabolic and physiologic interactions with the host. In this study, we performed genome analyses of more than 1,000 bifidobacterial strains publicly available revealing that Bifidobacterium adolescentis taxon might represent a model GABA producer in human gastrointestinal tract. Moreover, the in silico screening of human/animal metagenomic datasets showed an intriguing association/correlation between B. adolescentis load and mental disorders such as depression and anxiety. Interestingly, in vitro screening of 82 B. adolescentis strains allowed identifying two high GABA producers, i.e. B. adolescentis PRL2019 and B. adolescentis HD17T2H, which were employed in an in vivo trial in rats. Feeding Groningen rats with a supplementation of B. adolescentis strains, confirmed the ability of these microorganisms to stimulate the in vivo production of GABA highlighting their potential implication in gut–brain axis interactions.
Publisher: Elsevier BV
Date: 09-2020
Publisher: Elsevier BV
Date: 08-2019
DOI: 10.1016/J.BBI.2019.03.009
Abstract: The inflammatory reflex is known as the body's primary defense against infection and has been implicated in a number of diseases. The magnitude of the inflammatory response is important, as an extreme or insufficient response can be differentially harmful to the in idual. Converging evidence suggests that the autonomic nervous system (ANS) regulates the inflammatory reflex. Heart rate variability (HRV) can be separated into components that primarily reflect parasympathetic (PNS) or vagal activity (i.e., indices of vagally mediated HRV) and a combination of both sympathetic (SNS) and PNS influences. Given the physiological relation between the vagus and inflammatory processes, one would expect to find higher HRV, especially indices of vagally-mediated HRV, to be associated with decreased levels of inflammation via the cholinergic anti-inflammatory pathway. However, existing findings here are mixed, such that studies have also shown a positive association between indices of HRV and markers of inflammation. Therefore, the present meta-analysis aimed to synthesize existing studies, estimating the general direction and strength of the relationship between different indices of HRV and inflammatory markers. A systematic search of the literature yielded 2283 studies that were screened for inclusion eligibility (159 studies eligible for inclusion) in sum, 51 studies reported rovided adequate information for inclusion in meta-analyses. Results generally showed negative associations between indices of HRV and markers of inflammation. In this regard, the standard deviation of R-R intervals (SDNN) and power in the high frequency band of HRV (HF-HRV) showed the strongest and most robust associations with inflammatory markers compared to other time- and frequency-domain measures of HRV. Overall, we propose that indices of HRV can be used to index activity of the neurophysiological pathway responsible for adaptively regulating inflammatory processes in humans.
Publisher: PeerJ
Date: 13-01-2021
DOI: 10.7717/PEERJ.10610
Abstract: The healthcare provider profession strongly relies on the ability to care for others’ emotional experiences. To what extent burnout may relate to an actual alteration of this key professional ability has been little investigated. In an experimentally controlled setting, we investigated whether subjective experiences of global burnout or burnout depersonalization (the interpersonal component of burnout) relate to objectively measured alterations in emotion recognition and to what extent such alterations are emotion specific. Healthcare workers ( n = 90) completed the Maslach Burnout Inventory and a dynamic emotion recognition task in which faces with neutral emotional expressions gradually changed to display a specific basic emotion (happiness, anger, fear, or sadness). Participants were asked to identify and then classify each displayed emotion. Before the task, a subs le of 46 participants underwent two salivary cortisol assessments. In iduals with global burnout were less accurate at recognizing others’ emotional expressions of anger and fear, tending to misclassify these as happiness, compared to in iduals without global burnout. In iduals with high burnout depersonalization were more accurate in recognizing happiness and less accurate in recognizing all negative emotions, with a tendency to misclassify the latter as positive ones, compared to healthcare workers with moderate/low depersonalization. Moreover, in iduals with high depersonalization—but not participants with global burnout—were characterized by higher cortisol levels. These results suggest that the subjective burnout experience relates to an actual, but selective, reduction in the recognition of facial emotional expressions, characterized by a tendency to misclassify negative emotional expressions as positive ones, perhaps due to an enhanced seeking of positive social cues. This study adds to the understanding of emotional processing in burnout and paves the way for more nuanced studies on the role of altered processing of threat signals in the development and/or persistence of burnout.
Publisher: Cold Spring Harbor Laboratory
Date: 23-06-2021
DOI: 10.1101/2021.06.17.21259071
Abstract: Due to its ability to reflect the capacity to engage in context-appropriate responses, tonic heart rate variability (HRV) is considered a putative biomarker of stress resilience. However, most studies are cross-sectional, precluding causal inferences. The high levels of uncertainty and fear at a global level that characterize the COVID-19 pandemic offer a unique opportunity to investigate the longitudinal role of HRV in stress resilience. The present study examined whether HRV, measured about 2 years earlier (Time 0), could predict emotion regulation strategies and daily affect in healthy adults during the May 2020 lockdown (Time 1). Moreover, we evaluated the association between HRV measures, emotion regulation strategies, subjective perception of COVID-19 risk, and self-reported depressive symptoms at Time 1. Higher tonic HRV at Time 0 resulted a significant predictor of a stronger engagement in more functional emotion regulation strategies, as well as of higher daily feelings of safeness and reduced daily worry at Time 1. Moreover, depressive symptoms negatively correlated with HRV and positively correlated with the subjective perception of COVID-19 risk at Time 1. Current data support the view that HRV might be not only a marker but also a precursor of resilience under stressful times.
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.NEUBIOREV.2016.04.013
Abstract: Numerous studies have documented a link between psychological disorders and cardiac disease. Yet, no systematic attempts have been made to develop pharmacological approaches for mood and anxiety disorders that could also be beneficial for cardiac health. The endocannabinoid system has been implicated in the regulation of stress, emotional behavior and cardiovascular function. General preclinical findings indicate that the endocannabinoid anandamide modulates physiological and behavioral stress responses and may also protect the heart from arrhythmias. Moreover, recent experimental studies suggest that pharmacological enhancement of anandamide signaling via inhibition of its degrading enzyme fatty acid amide hydrolase (FAAH) exerts anxiolytic- and antidepressive-like effects and improves cardiac autonomic function and the electrical stability of the myocardium in rodent models that reproduce aspects of human psychological/cardiac comorbidity. Here we summarize and discuss such experimental findings, which might guide future preclinical studies towards a systematic evaluation of the therapeutic potential of pharmacological approaches that target FAAH activity for the treatment of the comorbidity between psychological disorders and cardiac disease.
Publisher: Public Library of Science (PLoS)
Date: 31-05-2019
Publisher: Elsevier BV
Date: 03-2017
DOI: 10.1016/J.NEUBIOREV.2016.05.003
Abstract: Psychological resilience can be defined as in idual's ability to withstand and adapt to adverse and traumatic events. Resilience is traditionally assessed by subjective reports, a method that is susceptible to self-report bias. An ideal solution to this challenge is the introduction of standardised and validated physiological and/or biological predictors of resilience. We provide a summary of the major concepts in the field of resilience followed by a detailed critical review of the literature around physiological, neurochemical and immune markers of resilience. We conclude that in future experimental protocols, biological markers of resilience should be assesses both during baseline and during laboratory stressors. In the former case the most promising candidates are represented by heart rate variability and by in vitro immune cells assay in the latter case-by startle responses (especially their habituation) during stress challenge and by cardiovascular recovery after stress, and by cortisol, DHEA and cytokine responses. Importantly, they should be used in combination to enhance predictive power.
Publisher: Elsevier BV
Date: 11-2022
Publisher: Elsevier BV
Date: 09-2018
DOI: 10.1016/J.IJPSYCHO.2017.11.002
Abstract: Ruminative thinking about negative feelings has been prospectively associated with increases in depressive symptoms and heightened risk for new onsets of major depression. One putative pathophysiological mechanism underlying this link might be represented by autonomic nervous system dysfunction. The objective of this longitudinal study was to evaluate the interplay between rumination, autonomic function (as revealed by heart rate variability (HRV) analysis), and depressive symptoms in healthy young subjects, over a three-year period. Rumination and depressive symptoms were evaluated in twenty-two women and twenty men at three assessment points (Time 0, 1 and 2) by the score on the Ruminative Response Scale, and the Center for Epidemiological Studies Depression Scale, respectively. Vagally-mediated HRV was assessed in a laboratory session (Time 0) and in two ambulatory sessions at Time 1 and Time 2 (~13 and 34months after Time 0, respectively). Ruminative thinking was found to be (i) a stable trait characteristic, (ii) more prevalent in women than men, and (iii) positively correlated with depressive symptoms. Moreover, resting HRV was negatively correlated with both rumination and depressive symptoms. Finally, HRV at Time 1 mediated the relationship between rumination at Time 0 and depressive symptoms at Time 2. We conclude that autonomic dysfunction, specifically low vagal tone, may be prospectively implicated in the generation of depressive symptoms in a non-clinical setting.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.CLINPH.2018.10.001
Abstract: Seizures are frequently observed in neurological conditions affecting newborns. Since autonomic alterations are commonly associated with neonatal seizures (NS), we investigated the utility of heart rate variability (HRV) indexes of cardiac autonomic regulation for NS detection. HRV analysis was conducted on ECG tracings recorded during video-EEG monitoring in newborns with NS and matched-controls. The effects of gestational age on HRV were also evaluated. Newborns with NS showed lower resting state HRV compared to controls. Moreover, seizure episodes were characterized by a short-lasting increase in vagal indexes of HRV. Pre-term newborns with NS had a lower HRV than full-term at rest. In pre-term newborns, no changes in HRV were observed before and during NS. On the contrary, full-term newborns showed significantly higher HRV before and during NS compared to the respective baseline values. Our data point to resting autonomic impairment in newborns with NS. In addition, an increment in HRV has been observed during NS only in full term newborns. Although these findings do not allow validation of HRV measures for NS prediction and detection, they suggest that a putative protective vagal mechanism might be adopted when an advanced maturation of autonomic nervous system is achieved.
Publisher: Informa UK Limited
Date: 21-12-2012
DOI: 10.3109/10253890.2011.639414
Abstract: Early life adverse experiences have long-term physiologic and behavioral effects and enhance stress sensitivity. This study examined the effects of maternal separation (MS) on cardiac stress responsivity and structure in adulthood. Male Wistar rats were separated from the dams for 3 h per day from postnatal days 2 through 15. When exposed to 5-day intermittent restraint stress (IRS) as adults, MS, and control rats showed similar acute modifications of cardiac sympathovagal balance, quantified via heart rate variability analysis. In addition, MS had no effect on cardiac pacemaker intrinsic activity (as revealed by autonomic blockade with scopolamine and atenolol) and did not affect the circadian rhythmicity of heart rate, neither before nor after IRS. However, MS differed from control rats in cardiac parasympathetic drive following IRS, which was heightened in the latter but remained unchanged in the former, both during the light and dark phases of the daily rhythm. The evaluation of adult cardiac structure indicated that stress experienced during a crucial developmental period induced only modest changes, involving cardiomyocyte hypertrophy, increased density of vascular structures, and myocardial fibrosis. The mildness of these functional-structural effects questions the validity of MS as a model for early stress-induced cardiac disease in humans.
Publisher: Frontiers Media SA
Date: 29-11-2019
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.PSYNEUEN.2018.11.003
Abstract: The two stress-responsive physiological systems, autonomic nervous system (ANS) and hypothalamus-pituitary-adrenal (HPA) axis exert complementary and interrelated actions in the organism. In iduals that suffer stress-related psychopathologies frequently present simultaneous alterations -i.e., either low or high- responsiveness- in both systems. However, there is scarce evidence establishing whether a priori alterations in these systems -i.e., independent of previous stress exposure- may predispose to the development of psychopathologies possibly due to the lack of animal models simultaneously involving aberrant HPA and SNS responses. In this study, we describe two animal models selectively bred according to their differential (either high, 'High', or low, 'Low') glucocorticoid responsiveness to stress, in comparison to a third line of rats that displays intermediate ('Inter') glucocorticoid responses. The two extreme lines may be considered distinct models of psychopathology the High line representing a model of constitutive mood alterations while the Low line a model of vulnerability to develop stress-induced psychopathologies. We recorded the electrocardiogram in rats from the three lines and quantified heart rate variability and vagal tone indexes during rest and stress challenges. Rats from both High and Low lines displayed higher heart rate and lower basal vagal tone than the Inter group, both at resting and following stress exposure. Specific pharmacological manipulations probing the relative contribution of sympathetic and parasympathetic components on HR modulation confirmed a relative lower vagal tone in High and Low lines and discarded differences in the sympathetic regulation of heart rate between the lines. Therefore, the two genetically-selected High and Low glucocorticoid rat lines emerge as two valuable preclinical models of psychopathology involving two key risk factors for psychiatric and cardiovascular disorders, namely dysregulations in the HPA axis and cardiac vagal functioning.
Publisher: Springer Science and Business Media LLC
Date: 06-04-2023
Publisher: Informa UK Limited
Date: 09-11-2021
DOI: 10.1080/10253890.2021.1999408
Abstract: Resting heart rate variability (HRV), a surrogate index of cardiac vagal modulation, is considered a putative biomarker of stress resilience as it reflects the ability to effectively regulate emotions in a changing environment. However, most studies are cross-sectional, precluding longitudinal inferences. The high degree of uncertainty and fear at a global level that characterizes the COVID-19 pandemic offers a unique opportunity to explore the utility of HRV measures as longitudinal predictors of stress resilience. This study examined whether resting measures of HRV prior to the COVID-19 outbreak (i.e. nearly 2 years before Time 0) could predict emotion regulation strategies and daily affect in healthy adults during the May 2020 lockdown (Time 1). Moreover, we evaluated the association between HRV measures, emotion regulation strategies, subjective perception of COVID-19 risk, and self-reported depressive symptoms at Time 1. Higher resting HRV at Time 0 predicted a stronger engagement in more functional emotion regulation strategies, as well as of higher daily feelings of safeness and reduced daily worry at Time 1. Moreover, depressive symptoms negatively correlated with HRV and positively correlated with the subjective perception of COVID-19 risk at Time 1. Current data support the view that HRV might not only be a marker but also a precursor of resilience under stressful times.
Publisher: Springer Science and Business Media LLC
Date: 08-04-2019
DOI: 10.1038/S41598-019-42257-Z
Abstract: Chitin-glucan (CG) represents a natural carbohydrate source for certain microbial inhabitants of the human gut and may act as a prebiotic for a number of bacterial taxa. However, the bifidogenic activity of this substrate is still unknown. In the current study, we evaluated the ability of chitin-glucan to influence growth of 100 bifidobacterial strains belonging to those species commonly identified within the bifidobacterial communities residing in the infant and adult human gut. Such analyses were coupled with transcriptome experiments directed to explore the transcriptional effects of CG on Bifidobacterium breve 2L, which was shown to elicit the highest growth performance on this natural polysaccharide. In addition, an in vivo trial involving a rat model revealed how the colonization efficiency of this bifidobacterial strain was enhanced when the animals were fed with a diet containing CG. Altogether our analyses indicate that CG is a valuable novel prebiotic compound that may be added to the human diet in order to re-establish/reinforce bifidobacteria colonization in the mammalian gut.
Publisher: Informa UK Limited
Date: 06-07-2021
DOI: 10.1080/10253890.2021.1942830
Abstract: This study investigated epigenetic risk factors that may contribute to stress-related cardiac disease in a rodent model. Experiment 1 was designed to evaluate the expression of microRNA-34a (miR-34a), a known modulator of both stress responses and cardiac pathophysiology, in the heart of male adult rats exposed to a single or repeated episodes of social defeat stress. Moreover, RNA sequencing was conducted to identify transcriptomic profile changes in the heart of repeatedly stressed rats. Experiment 2 was designed to assess cardiac electromechanical changes induced by repeated social defeat stress that may predispose rats to cardiac dysfunction. Results indicated a larger cardiac miR-34a expression after repeated social defeat stress compared to a control condition. This molecular modification was associated with increased vulnerability to pharmacologically induced arrhythmias and signs of systolic left ventricular dysfunction. Gene expression analysis identified clusters of differentially expressed genes in the heart of repeatedly stressed rats that are mainly associated with morphological and functional properties of the mitochondria and may be directly regulated by miR-34a. These results suggest the presence of an association between miR-34a overexpression and signs of adverse electromechanical remodeling in the heart of rats exposed to repeated social defeat stress, and point to compromised mitochondria efficiency as a potential mediator of this link. This rat model may provide a useful tool for investigating the causal relationship between miR-34a expression, mitochondrial (dys)function, and cardiac alterations under stressful conditions, which could have important implications in the context of stress-related cardiac disease.
Publisher: Elsevier BV
Date: 04-2017
DOI: 10.1016/J.PHYSBEH.2016.07.017
Abstract: Central neuropeptide Y (NPY) signaling participates in the regulation of cardiac autonomic outflow, particularly via activation of NPY-Y1 receptors (Y1Rs). However, the specific brain areas and neural pathways involved have not been completely identified yet. Here, we evaluate the role of hippoc al Y1Rs in the modulation of the autonomic control of cardiac function using a conditional knockout mouse model. Radiotelemetric transmitters were implanted in 4-month-old male mice exhibiting reduced forebrain expression (rfb) of the Y1R (Npy1r
Publisher: Elsevier BV
Date: 08-2017
DOI: 10.1016/J.PSYNEUEN.2017.05.017
Abstract: The negative emotional consequences associated with life stress exposure in an in idual can affect the emotional state of social partners. In this study, we describe an experimental rat model of social stress contagion and its effects on social behaviour and cardiac autonomic and neuroendocrine functions. Adult male Wistar rats were pair-housed and one animal (designated as "demonstrator" (DEM)) was submitted to either social defeat stress (STR) by an aggressive male Wild-type rat in a separate room or just exposed to an unfamiliar empty cage (control condition, CTR), once a day for 4 consecutive days. We evaluated the influence of cohabitation with a STR DEM on behavioural, cardiac autonomic and neuroendocrine outcomes in the cagemate (defined "observer" (OBS)). After repeated social stress, STR DEM rats showed clear signs of social avoidance when tested in a new social context compared to CTR DEM rats. Interestingly, also their cagemate STR OBSs showed higher levels of social avoidance compared to CTR OBSs. Moreover, STR OBS rats exhibited a higher heart rate and a larger shift of cardiac autonomic balance toward sympathetic prevalence (as indexed by heart rate variability analysis) immediately after the first reunification with their STR DEMs, compared to the control condition. This heightened cardiac autonomic responsiveness habituated over time. Finally, STR OBSs showed elevated plasma corticosterone levels at the end of the experimental protocol compared to CTR OBSs. These findings demonstrate that cohabitation with a DEM rat, which has experienced repeated social defeat stress, substantially disrupts social behaviour and induces short-lasting cardiac autonomic activation and hypothalamic-pituitary-adrenal axis hyperactivity in the OBS rat, thus suggesting emotional state-matching between the OBS and the DEM rats. We conclude that this rodent model may be further exploited for investigating the neurobiological bases of negative affective sharing between social partners under chronic social stress conditions.
Publisher: Frontiers Media SA
Date: 06-04-2018
Publisher: American Physiological Society
Date: 03-2017
DOI: 10.1152/AJPHEART.00366.2016
Abstract: Single high-intensity premature stimuli when applied to the ventricles during ventricular drive of an ectopic site, as in Winfree's “pinwheel experiment,” usually induce reentry arrhythmias in the normal heart, while single low-intensity stimuli barely do. Yet ventricular arrhythmia vulnerability during normal sinus rhythm remains largely unexplored. With a view to define the role of anisotropy on ventricular vulnerability to unidirectional conduction block and reentry, we revisited the pinwheel experiment with reduced constraints in the in situ rat heart. New features included single premature stimulation during normal sinus rhythm, stimulation and unipolar potential mapping from the same high-resolution epicardial electrode array, and progressive increase in stimulation strength and prematurity from diastolic threshold until arrhythmia induction. Measurements were performed with 1-ms cathodal stimuli at multiple test sites ( n = 26) in seven rats. Stimulus-induced virtual electrode polarization during sinus beat recovery phase influenced premature ventricular responses. Specifically, gradual increase in stimulus strength and prematurity progressively induced make, break, and graded-response stimulation mechanisms. Hence unidirectional conduction block occurred as follows: 1) along fiber direction, on right and left ventricular free walls ( n = 23), initiating figure-eight reentry ( n = 17) and tachycardia ( n = 12), and 2) across fiber direction, on lower interventricular septum ( n = 3), initiating spiral wave reentry ( n = 2) and tachycardia ( n = 1). Critical time window (55.1 ± 4.7 ms, 68.2 ± 6.0 ms) and stimulus strength lower limit (4.9 ± 0.6 mA) defined vulnerability to reentry. A novel finding of this study was that ventricular tachycardia evolves and is maintained by episodes of scroll-like wave and focal activation couplets. We also found that single low-intensity premature stimuli can induce repetitive ventricular response ( n = 13) characterized by focal activations. NEW & NOTEWORTHY We performed ventricular cathodal point stimulation during sinus rhythm by progressively increasing stimulus strength and prematurity. Virtual electrode polarization and recovery gradient progressively induced make, break, and graded-response stimulation mechanisms. Unidirectional conduction block occurred along or across fiber direction, initiating figure-eight or spiral wave reentry, respectively, and tachycardia sustained by scroll wave and focal activations.
Publisher: Public Library of Science (PLoS)
Date: 17-04-2014
Publisher: Springer Science and Business Media LLC
Date: 26-09-2018
DOI: 10.1007/S11886-018-1064-X
Abstract: This review offers a perspective of the utility of rodent models of stress for identifying sources of in idual vulnerability to depression and cardiovascular disease comorbidity. Differential stress susceptibility is found in rodents exposed to repeated social defeat as a function of their coping style. Specifically, passive coping rodents show an increase in inflammatory processes within the brain that favour the development of depressive-like symptoms and cardiovascular abnormalities. Similarly, only a sub-group of rats develops depressive-like symptoms following chronic mild stress exposure. Cardiovascular changes differ depending on in idual stress susceptibility and may be related to an imbalance in the autonomic regulation of cardiac function in stress vulnerable subjects. Rodent models of stress that take into account in idual phenotypic variations are useful for a better understanding of the role of neuroinflammatory and autonomic processes in the development of comorbid depression and cardiovascular disease under stressful conditions.
Publisher: Frontiers Media SA
Date: 07-10-2020
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2013
Publisher: Wiley
Date: 20-06-2019
DOI: 10.1002/SMI.2870
Abstract: Stress related to parenting a child with autism spectrum disorder can differently affect caregiver's physiological reactivity to acute stress. Here, parental stress levels, psychological characteristics, and coping strategies were assessed alongside measures of heart rate, heart rate variability, and cortisol during a psychosocial stress test in mothers of children with ASD (M-ASD, n = 15) and mothers of typically developing children (n = 15). M-ASD reported significantly higher levels of parental stress, anxiety, negative affectivity, social inhibition, and a larger preference for avoidance strategies. M-ASD showed larger heart rate and cortisol responses to the psychosocial stress test. A positive relationship was found between parental stress levels and the magnitude of the cortisol stress response in both groups. The present findings indicate exaggerated physiological reactivity to acute psychosocial stress in M-ASD and prompt further research to explore the role of in idual differences in mediating the effects of parental stress on physiological stress responses.
Publisher: Public Library of Science (PLoS)
Date: 04-07-2013
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.PHYSBEH.2014.01.033
Abstract: In humans, there is a documented association between anxiety disorders and cardiovascular disease. Putative underlying mechanisms may include an impairment of the autonomic nervous system control of cardiac function. The primary objective of the present study was to characterize cardiac autonomic modulation and susceptibility to arrhythmias in genetic lines of rats that differ largely in their anxiety level. To reach this goal, electrocardiographic recordings were performed in high-anxiety behavior (HAB, n=10) and low-anxiety behavior (LAB, n=10) rats at rest, during stressful stimuli and under autonomic pharmacological manipulations, and analyzed by means of time- and frequency-domain indexes of heart rate variability. During resting conditions, HAB rats displayed a reduced heart rate variability, mostly in terms of lower parasympathetic (vagal) modulation compared to LAB rats. In HAB rats, this relatively low cardiac vagal control was associated with smaller heart rate responsiveness to acute stressors compared to LAB counterparts. In addition, beta-adrenergic pharmacological stimulation induced a larger incidence of ventricular tachyarrhythmias in HABs compared to LABs. At sacrifice, a moderate increase in heart-body weight ratio was observed in HAB rats. We conclude that high levels of anxiety-related behavior in rats are associated with signs of i) impaired autonomic modulation of heart rate (low vagally-mediated heart rate variability), ii) poor adaptive heart rate responsiveness to stressful stimuli, iii) increased arrhythmia susceptibility, and iv) cardiac hypertrophy. These results highlight the utility of the HAB/LAB model for investigating the mechanistic basis of the comorbidity between anxiety disorders and cardiovascular disease.
Publisher: PAGEPress Publications
Date: 10-01-2014
Abstract: Cardiovascular disease increases with age as well as alterations of cardiac electrophysiological properties, but a detailed knowledge about changes in cardiac electrophysiology relevant to arrhythmogenesis in the elderly is relatively lacking. The aim of this study was to determine specific age-related changes in electrophysiological properties of the ventricles which can be related to a structural-functional arrhythmogenic substrate. Multiple epicardial electrograms were recorded on the ventricular surface of in vivo control and aged rats, while arrhythmia vulnerability was investigated by premature stimulation protocols. Single or multiple ectopic beats and sustained ventricular arrhythmias were frequently induced in aged but not in control hearts. Abnormal ventricular activation patterns during sinus rhythm and unchanged conduction velocity during point stimulation in aged hearts suggest the occurrence of impaired impulse conduction through the distal Purkinje system that might create a potential reentry substrate.
Publisher: Elsevier BV
Date: 03-2020
DOI: 10.1016/J.EURONEURO.2019.12.119
Abstract: Pharmacological inhibition of the enzyme fatty acid amide hydrolase (FAAH), which terminates signaling of the endocannabinoid N-arachidonoylethanolamine (or anandamide, AEA), exerts favourable effects in rodent models of stress-related depression. Yet although depression seems to be more common among women than men and in spite of some evidence of sex differences in treatment efficacy, preclinical development of FAAH inhibitors for the pharmacotherapy of stress-related depression has been predominantly conducted in male animals. Here, adult female rats were exposed to six weeks of social isolation and, starting from the second week, treated with the FAAH inhibitor URB694 (0.3 mg/kg/day, i.p.) or vehicle. Compared to pair-housed females, socially isolated female rats treated with vehicle developed behavioral (mild anhedonia, passive stress coping) and physiological (reduced body weight gain, elevated plasma corticosterone levels) alterations. Moreover, prolonged social isolation provoked a reduction in brain-derived neurotrophic factor (BDNF) and AEA levels within the hippoc us. Together, these changes are indicative of an increased risk of developing a depressive-like state. Conversely, pharmacological inhibition of FAAH activity with URB694 restored both AEA and BDNF levels within the hippoc us of socially isolated rats and prevented the development of behavioral and physiological alterations. These results suggest a potential interplay between AEA-mediated signaling and hippoc al BDNF in the pathogenesis of depression-relevant behaviors and physiological alterations and antidepressant action of FAAH inhibition in socially isolated female rats.
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.NEUBIOREV.2020.01.011
Abstract: Stressful experiences can be transmitted among in iduals through social interactions. Like humans, rodents are social creatures whose behavior and physiology can be influenced by the emotional state of fellow rodents. This paper will review rodent studies which have explored two conditions of potential social stress contagion using the social defeat paradigm. In the vicarious social defeat model, mice and rats that witness a conspecific being socially defeated exhibit physiological stress responses and develop a host of depressive- and anxiety-like behavioral deficits. Likewise, social interaction with a stressed partner in the aftermath of social defeat stress results in physiological stress responses and social avoidance behavior. After summarizing the existing literature on this newly emerging area of social defeat stress contagion in rodents, we will discuss the potential utility of these rodent models for investigating the neurobiological processes and sensory channels of information that allow for the spread of psychophysiological effects of stress across in iduals.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.EURONEURO.2015.07.015
Abstract: In humans, depression is often triggered by prolonged exposure to psychosocial stressors and is often associated with cardiovascular comorbidity. Mounting evidence suggests a role for endocannabinoid signaling in the regulation of both emotional behavior and cardiovascular function. Here, we examined cardiac activity in a rodent model of social stress-induced depression and investigated whether pharmacological inhibition of the enzyme fatty acid amide hydrolase (FAAH), which terminates signaling of the endocannabinoid anandamide, exerts antidepressant-like and cardioprotective effects. Male Wistar Kyoto rats were exposed to five weeks of repeated social stress or control procedure. Starting from the third week, they received daily administration of the selective FAAH inhibitor URB694 (0.1 mg/kg, i.p.) or vehicle. Cardiac electrical activity was recorded by radiotelemetry. Repeated social stress triggered biological and behavioral changes that mirror symptoms of human depression, such as (i) reductions in body weight gain and sucrose solution preference, (ii) hyperactivity of the hypothalamic-pituitary-adrenocortical axis, and (iii) increased immobility in the forced swim test. Moreover, stressed rats showed (i) alterations in heart rate daily rhythm and cardiac autonomic neural regulation, (ii) a larger incidence of spontaneous arrhythmias, and (iii) signs of cardiac hypertrophy. Daily treatment with URB694 (i) increased central and peripheral anandamide levels, (ii) corrected stress-induced alterations of biological and behavioral parameters, and (iii) protected the heart against the adverse effects of social stress. Repeated social stress in Wistar Kyoto rats reproduces aspects of human depression/cardiovascular comorbidity. Pharmacological enhancement of anandamide signaling might be a promising strategy for the treatment of these comorbid conditions.
Publisher: Elsevier BV
Date: 02-2019
Publisher: Elsevier BV
Date: 03-2019
DOI: 10.1016/J.AUTNEU.2019.01.001
Abstract: Generalized anxiety disorder (GAD) is associated with both autonomic dysfunction, notably decreased vagally-mediated heart rate variability (vmHRV), and neurostructural abnormalities. Regional differences in brain morphometry correlate with vmHRV in healthy in iduals. Here, we tested the hypothesis that specific focal abnormalities in cortical structure in GAD underpin decreased vmHRV. Adult female patients with GAD (n = 17) and matched controls (n = 18) underwent structural magnetic resonance imaging after characterization of symptoms and quantification of resting vmHRV derived from continuous pulse oximetry. Cortical reconstruction was performed using the FreeSurfer image analysis suite. A priori analysis was conducted only within brain regions involved in vagal control of heart rate. Compared to controls, patients with GAD showed cortical thinning of the (i) left rostral anterior cingulate cortex, (ii) left medial orbitofrontal cortex, and (iii) right isthmus cingulate gyrus. Significant negative relationships were identified between the severity of anxiety symptoms and cortical thickness of the left medial orbitofrontal cortex and right isthmus cingulate gyrus. Compared to controls, patients with GAD showed decreased vmHRV at rest. In controls only, cortical thickness of the left caudal anterior cingulate cortex correlated positively with resting vmHRV. These results extend evidence in GAD for structural abnormalities within cortical areas implicated in emotion regulation and cognition. In addition, these findings may implicate abnormal integrity of anterior cingulate cortex in the psychophysiological expression of GAD and suggest that interventional targeting of this region may normalize autonomic function in GAD.
Publisher: Wiley
Date: 14-05-2023
DOI: 10.1111/APHA.13981
Abstract: Nfix is a transcription factor belonging to the Nuclear Factor I (NFI) family comprising four members ( Nfia , b , c , x ). Nfix plays important roles in the development and function of several organs. In muscle development , Nfix controls the switch from embryonic to fetal myogenesis by promoting fast twitching fibres. In the adult muscle, following injury, lack of Nfix impairs regeneration, inducing higher content of slow‐twitching fibres. Nfix is expressed also in the heart, but its function has been never investigated before. We studied Nfix role in this organ. Using Nfix ‐null and wild type (WT) mice we analyzed: (1) the expression pattern of Nfix during development by qPCR and (2) the functional alterations caused by its absence, by in vivo telemetry and in vitro patch cl analysis. Nfix expression start in the heart from E12.5. Adult hearts of Nfix ‐null mice show a hearts morphology and sarcomeric proteins expression similar to WT. However, Nfix ‐null animals show tachycardia that derives form an intrinsic higher beating rate of the sinus node (SAN). Molecular and functional analysis revealed that sinoatrial cells of Nfix ‐null mice express a significantly larger L‐type calcium current ( Cacna1d + Cacna1c ). Interestingly, downregulation of Nfix by sh‐RNA in primary cultures of neonatal rat ventricular cardiomyocytes induced a similar increase in their spontaneous beating rate and in I CaL current. In conclusion, our data provide the first demonstration of a role of Nfix that, increasing the L‐type calcium current, modulates heart rate.
Publisher: Frontiers Media SA
Date: 17-05-2021
DOI: 10.3389/FNINS.2021.617698
Abstract: The aim of this study was to assess age-related changes in cardiac autonomic modulation and heart rate variability (HRV) and their association with spontaneous and pharmacologically induced vulnerability to cardiac arrhythmias, to verify the translational relevance of mouse models for further in-depth evaluation of the link between autonomic changes and increased arrhythmic risk with advancing age. Heart rate (HR) and time- and frequency-domain indexes of HRV were calculated from Electrocardiogram (ECG) recordings in two groups of conscious mice of different ages (4 and 19 months old) (i) during daily undisturbed conditions, (ii) following peripheral β-adrenergic (atenolol), muscarinic (methylscopolamine), and β-adrenergic + muscarinic blockades, and (iii) following β-adrenergic (isoprenaline) stimulation. Vulnerability to arrhythmias was evaluated during daily undisturbed conditions and following β-adrenergic stimulation. HRV analysis and HR responses to autonomic blockades revealed that 19-month-old mice had a lower vagal modulation of cardiac function compared with 4-month-old mice. This age-related autonomic effect was not reflected in changes in HR, since intrinsic HR was lower in 19-month-old compared with 4-month-old mice. Both time- and frequency-domain HRV indexes were reduced following muscarinic, but not β-adrenergic blockade in younger mice, and to a lesser extent in older mice, suggesting that HRV is largely modulated by vagal tone in mice. Finally, 19-month-old mice showed a larger vulnerability to both spontaneous and isoprenaline-induced arrhythmias. The present study combines HRV analysis and selective pharmacological autonomic blockades to document an age-related impairment in cardiac vagal modulation in mice which is consistent with the human condition. Given their short life span, mice could be further exploited as an aged model for studying the trajectory of vagal decline with advancing age using HRV measures, and the mechanisms underlying its association with proarrhythmic remodeling of the senescent heart.
Publisher: Elsevier BV
Date: 05-2012
DOI: 10.1016/J.PHYSBEH.2012.01.022
Abstract: Adverse social environments play a relevant role in the onset and progression of mood disorders. On the other hand, depression is an independent risk factor for cardiovascular morbidity. This study was aimed at (i) corroborating the validity of a rat model of depression based on a negative social episode followed by social isolation and (ii) verifying its impact on cardiac function and structure. Pair housed, wild-type Groningen rats (Rattus norvegicus) were implanted with radiotransmitters for ECG, temperature and activity recordings. They were either exposed to a social defeat episode followed by 4-week isolation or left undisturbed with their female partners. The social challenge induced a series of biological changes that are commonly taken as markers of depression in rats, including decreased body weight gain and reduced preference for sucrose consumption, functional and structural changes of the hypothalamic-pituitary-adrenocortical axis, increased anxiety in the elevated plus maze test. The cardiovascular alterations consisted in (i) transitory heart rate circadian rhythm alterations, (ii) lack of habituation of cardiac autonomic responsivity (tachycardia and vagal withdrawal) to an acute stressor, and (iii) moderate hypertrophy affecting the right ventricle of the heart. These results indicate that a depression-like state induced via this model of social challenge was associated with a few modest cardiovascular changes. Further studies are required to confirm the validity of this rat model of depression as a valid preclinical approach to the comprehension of the biological substrates underlying depression-cardiovascular comorbidity.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.PHYSBEH.2016.09.028
Abstract: In humans, associations between anxiety and nausea (including motion-induced) are reported but the underlying mechanisms are not known. Hypothermia is proposed to be an index of nausea in rats. Utilising hypothermia and heart rate as outcome measures we investigated the response to provocative motion in rats selectively bred for high (HAB) and low (LAB) anxiety-related behaviors and in non-selected (NAB) rats to further elucidate the potential relationship between hypothermia and nausea-like state. Core temperature and electrocardiogram were monitored in each group (n=10 per group) using telemetry, with or without circular motion (40min 0.75Hz) and vehicle or diazepam (2mg/kg, i.p.) pre-treatment. Heart rate and time- and frequency-domain parameters of heart rate variability were derived from the electrocardiogram. There was no baseline difference in core temperature between the three groups (mean 38.0±0.1°C), but HAB animals had a significantly lower resting heart rate (330±7bpm) compared to LAB (402±5bpm) and NAB (401±9bpm). Animals in all groups exhibited hypothermia during motion (HAB: 36.3±0.1°C NAB: 36.4±0.1°C LAB: 34.9±0.2°C) with the magnitude (area under the curve, AUC) of the response during 40-min motion being greater in LAB compared to NAB and HAB rats, and this was also the case for the motion-induced bradycardia. Diazepam had minimal effects on baseline temperature and heart rate in all groups, but significantly reduced the hypothermia response (AUC) to motion in all groups by ~30%. Breeding for extremes in anxiety-related behavior unexpectedly selects animals with low trait anxiety that have enhanced bradycardia and hypothermic responses to motion consequently, this animal model appears to be not suitable for exploring relationships between anxiety and autonomic correlates of nausea. Thermal and cardiovascular responses to motion were little different between HAB and NAB rats indicating that either hypothermia is not an index of a nausea-like state in rats, or that the positive correlation between anxiety and nausea demonstrated in humans does not exist in rats. The mechanism underlying the enhanced physiological responses in LAB requires more detailed study and may provide a novel model to investigate factors modulating motion sensitivity.
Publisher: Walter de Gruyter GmbH
Date: 09-2017
Abstract: The efficacy of osteopathic manipulative therapy (OMTh manipulative care provided by foreign-trained osteopaths) is supported by observational data and patient feedback, but there is still a need for objective, quantitative biomarkers that allow measurement of the underlying mechanisms. No study exploring the protective potential of OMTh for mental stress has been published, to the authors’ knowledge. To explore the modulating effect of OMTh on autonomic neural regulation of the heart and verifiy its ability to influence the activity of the hypothalmic-pituitary-adrenocortical axis. Healthy young adult men who had never received OMTh were exposed to either a brief protocol using craniosacral techniques or sham therapy (control) involving the same anatomical areas. A laboratory stress episode consisting of a 5-minute arithmetic task participants were required to perform in front of a committee preceded the therapy sessions. Continuous electrocardiograph recordings were done before, during, and after the stress episode. Heart rate and frequency-domain parameters of heart rate variability (specifically, high-frequency component power in normalized units and the ratio of low-frequency to high-frequency power) were measured to quantify the activity of the parasympathetic nervous system and the state of sympathovagal balance at the level of the heart, respectively. Saliva s les were also collected at points throughout the study to determine cortisol levels. Osteopathic manipulative therapy reduced the overall chronotropic effect of the stressor ( t =−2.9, P .05) and counteracted the vagal withdrawal and the shift of autonomic balance toward sympathetic prevalence ( t =−2.8, P .05) that were observed in control participants. Moreover, OMTh participants had a much lower overall cortisol level during the mental stressor compared with control participants ( t =−2.3, P .05). Participants in the OMTh group did not show the statistically significant reduction in the litude of the cortisol awakening response observed in their control counterparts after the stress episode (control: t =2.7, P .05 OMT: P =.83). The application of a single OMTh session to healthy participants induced a faster recovery of heart rate and sympathovagal balance after an acute mental stressor by substantially d ening parasympathetic withdrawal and sympathetic prevalence. The OMTh session also prevented the typical increase in cortisol levels observed immediately after a brief mental challenge.
Publisher: American Physiological Society
Date: 10-2011
DOI: 10.1152/AJPREGU.00273.2011
Abstract: In humans, chronic stressors have long been recognized as potential causes for cardiac dysregulation. Despite this, the underlying mechanistic links responsible for this association are still poorly understood. The purpose of this study was to determine whether exposure to a paradigm of subchronic stress can provoke enduring changes on the heart rate of experimental rats and, if so, to reveal the autonomic and neural mechanisms that mediate these effects. The study was conducted on adult male Sprague-Dawley rats instrumented for telemetric recording of heart rate and locomotor activity. Animals were submitted to a subchronic stress protocol, consisting of a 1-h foot shock session on five consecutive days. Heart rate and locomotor activity were recorded continuously for 3 days before and for 6 days after the subchronic stress period. Subchronic foot shock produced significant and enduring reduction in heart rate both during the dark/active [Δ= −23 ± 3 beats per minute (bpm)] and light/inactive (Δ= −20 ± 3 bpm) phases of the circadian cycle, and a reduction in locomotor activity during the dark/active phase [Δ= −54 ± 6 counts per hour (cph)]. The bradycardic effect of subchronic stress was not related to a reduced locomotion. Selective sympathetic (atenolol) and vagal (methyl-scopolamine) blockades were performed to reveal which autonomic component was responsible for this effect. We found that the fall in heart rate persisted after subchronic stress in animals treated with atenolol (active phase Δ= −16 ± 3 bpm, inactive phase Δ= −19 ± 2 bpm), whereas vagal blockade with scopolamine transiently prevented this effect, suggesting that the bradycardia following subchronic stress was predominantly vagally mediated. Fluoxetine (selective serotonin reuptake inhibitor) and metyrapone (inhibitor of corticosterone synthesis) treatments did not affect heart rate changes but prevented the reduction in locomotion. We conclude that subchronic stress exposure in rats reduces heart rate via a rebound in vagal activation and that this effect is serotonin- and corticosterone-independent.
Publisher: Elsevier BV
Date: 11-2023
Publisher: Computing in Cardiology
Date: 30-12-2020
Location: Italy
Start Date: 2023
End Date: 2024
Funder: Università degli Studi di Parma
View Funded ActivityStart Date: 2021
End Date: 2024
Funder: Ministero della Salute
View Funded ActivityStart Date: 2022
End Date: 2025
Funder: Ministero dell'Università e della Ricerca
View Funded Activity