ORCID Profile
0000-0003-1067-5952
Current Organisation
Arizona State University
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: Springer Science and Business Media LLC
Date: 05-01-2022
DOI: 10.1038/S41380-021-01416-3
Abstract: The choroid plexus, a tissue responsible for producing cerebrospinal fluid, is found predominantly in the lateral and fourth ventricles of the brain. This highly vascularized and ciliated tissue is made up of specialized epithelial cells and capillary networks surrounded by connective tissue. Given the complex structure of the choroid plexus, this can potentially result in contamination during routine tissue dissection. Bulk and single-cell RNA sequencing studies, as well as genome-wide in situ hybridization experiments (Allen Brain Atlas), have identified several canonical markers of choroid plexus such as Ttr , Folr1 , and Prlr . We used the Ttr gene as a marker to query the Gene Expression Omnibus database for transcriptome studies of brain tissue and identified at least some level of likely choroid contamination in numerous studies that could have potentially confounded data analysis and interpretation. We also analyzed transcriptomic datasets from human s les from Allen Brain Atlas and the Genotype-Tissue Expression (GTEx) database and found abundant choroid contamination, with regions in closer proximity to choroid more likely to be impacted such as hippoc us, cervical spinal cord, substantia nigra, hypothalamus, and amygdala. In addition, analysis of both the Allen Brain Atlas and GTEx datasets for differentially expressed genes between likely “high contamination” and “low contamination” groups revealed a clear enrichment of choroid plexus marker genes and gene ontology pathways characteristic of these ciliated choroid cells. Inclusion of these contaminated s les could result in biological misinterpretation or simply add to the statistical noise and mask true effects. We cannot assert that Ttr or other genes roteins queried in targeted assays are artifacts from choroid contamination as some of these differentials may be due to true biological effects. However, for studies that have an unequal distribution of choroid contamination among groups, investigators may wish to remove contaminated s les from analyses or incorporate choroid marker gene expression into their statistical modeling. In addition, we suggest that a simple RT-qPCR or western blot for choroid markers would mitigate unintended choroid contamination for any experiment, but particularly for s les intended for more costly omic profiling. This study highlights an unexpected problem for neuroscientists, but it is also quite possible that unintended contamination of adjacent structures occurs during dissections for other tissues but has not been widely recognized.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.APPET.2016.09.010
Abstract: The expression of corticotropin-releasing factor (CRF), a neuropeptide that regulates endocrine and behavioral responses to stress, was assessed in the brain in rats prone or resistant to stress-induced binge-like eating of sucrose. Female Sprague-Dawley rats were subjected to unpredictable intermittent 1-h access to sucrose in non-stressful conditions or after exposure to three foot shock stress sessions. Experimental sessions were performed at metestrus, diestrus, and proestrus. The rats were assigned to the binge-like eating prone (BEP) or the binge-like eating resistant (BER) phenotypes according to the rats' persistently high or low sucrose intake following three stress sessions. The BEP rats displayed elevated consumption of sucrose in non-stressful conditions and an additional significant increase in sucrose intake in response to stress. Conversely, the BER rats showed lower sucrose intake in non-stressful conditions, and stress did not increase sucrose intake in this phenotype. The brain expression of CRF mRNA and plasma corticosterone levels were assessed 30 min after the last stress session at the diestrous phase of the estrous cycle. Stress triggered a significant increase in plasma corticosterone levels and strongly increased CRF mRNA expression in the paraventricular hypothalamic nucleus in the BER but not in the BEP rats. However, the BEP but not the BER rats demonstrated a significant increase in CRF mRNA expression in the bed nucleus of the stria terminalis (BNST) after stress. Hyporeactivity of the hypothalamic-pituitary-adrenal axis and the higher CRF expression in the BNST in BEP rats may contribute to stress-induced binge-like sucrose eating in the BEP phenotype.
Publisher: Springer Science and Business Media LLC
Date: 03-01-2020
DOI: 10.1007/S00213-019-05439-1
Abstract: Eating disorders are frequently triggered by stress and are more prevalent in women than men. First signs often appear during early adolescence, but the biological basis for the sex-specific differences is unknown. Central administration of native relaxin-3 (RLN3) peptide or chimeric/truncated analogues produces differential effects on food intake and HPA axis activity in adult male and female rats, but the precise role of endogenous RLN3 signalling in metabolic and neuroendocrine control is unclear. Therefore, we examined the effects of microRNA-induced depletion (knock-down) of RLN3 mRNA/(peptide) production in neurons of the brainstem nucleus incertus (NI) in female rats on a range of physiological, behavioural and neurochemical indices, including food intake, body weight, anxiety, plasma corticosterone, mRNA levels of key neuropeptides in the paraventricular nucleus of hypothalamus (PVN) and limbic neural activity patterns (reflected by c-fos mRNA). Validated depletion of RLN3 in NI neurons of female rats (n = 8) produced a small, sustained (~ 2%) decrease in body weight, an imbalance in food intake and an increase in anxiety-like behaviour in the large open field, but not in the elevated plus-maze or light/dark box. Furthermore, NI RLN3 depletion disrupted corticosterone regulation, increased oxytocin and arginine-vasopressin, but not corticotropin-releasing factor, mRNA, in PVN, and decreased basal levels of c-fos mRNA in parvocellular and magnocellular PVN, bed nucleus of stria terminalis and the lateral hypothalamic area, brain regions involved in stress and feeding. These findings support a role for NI RLN3 neurons in fine-tuning stress and neuroendocrine responses and food intake regulation in female rats.
Publisher: Wiley
Date: 12-2016
DOI: 10.1111/JNE.12439
Abstract: The present study examined the effects of chronic central administration of relaxin-3 (RLN3) on food intake, body weight and fat mass in intact and sterilised male and female rats, as well as on hypothalamic-pituitary-gonadal (HPG) axis activity in intact male and female rats that received i.c.v. infusions of RLN3 (400 pmol/day) or vehicle during a 14-day period. The intact RLN3-injected rats displayed a higher body weight than the vehicle-treated groups, and this increase was statistically significantly stronger in female rats compared to male rats. In addition, feed efficiency and gonadal white adipose tissue weight were higher in female RLN3-injected rats. Chronic i.c.v. administration of RLN3 activated the HPG axis in intact male rats, whereas inhibition of the HPG axis was observed in intact female rats. RLN3 significantly increased the plasma levels of luteinising hormone and follicular-stimulating hormone in male rats but not in female rats. Conversely, hypothalamic expression of gonadotrophin-releasing hormone mRNA was decreased by RLN3 in female rats but not in male rats. In addition, the plasma levels of oestradiol were significantly decreased by RLN3 administration in female rats. Consequently, intact RLN3-injected female rats failed to display phasic inhibition of eating during oestrus. Sex-specific effects of RLN3 on food intake and body weight were also observed in ovariectomised female and orchidectomised male rats, suggesting that the sex-specific effects of RLN3 on energy metabolism are independent on the differential effects of RLN3 on HPG axis activity in male and female rats.
Publisher: Elsevier BV
Date: 2018
DOI: 10.1016/J.BBR.2017.08.044
Abstract: The neuropeptide relaxin-3 (RLN3) binds with high affinity to its cognate receptor, relaxin-family peptide receptor 3 (RXFP3), and with lower affinity to RXFP1, the cognate receptor for relaxin. Intracerebroventricular (icv) administration of RLN3 in rats strongly increases food and water intake and alters the activity of the hypothalamic-pituitary-adrenal (HPA) and gonadal (HPG) axes, but the relative involvement of RXFP3 and RXFP1 in these effects is not known. Therefore, the effects of icv administration of equimolar (1.1 nmol) amounts of RLN3 and the RXFP3-selective agonist RXFP3-A2 on food and water intake, plasma levels of corticosterone, testosterone, and oxytocin and c-fos mRNA expression in key hypothalamic regions in male rats were compared. Food intake was increased by both RLN3 and RXFP3-A2, but the orexigenic effects of RXFP3-A2 were significantly stronger than RLN3, 30 and 60min after injection. Water intake and plasma corticosterone and testosterone levels were significantly increased by RLN3, but not by RXFP3-A2. Conversely, RXFP3-A2 but not RLN3 decreased oxytocin plasma levels. RLN3, but not RXFP3-A2, increased c-fos mRNA levels in the parvocellular (PVNp) and magnocellular (PVNm) paraventricular and supraoptic (SON) hypothalamic nuclei, in the ventral medial preoptic area (MPAv), and in the organum vasculosum of the lamina terminalis (OVLT). A significant increase in c-fos mRNA expression was induced in the perifornical lateral hypothalamic area (LHApf) by RLN3 and RXFP3-A2. These results suggest that RXFP1 is involved in the RLN3 stimulation of water intake and activation of the HPA and HPG axes. The reduced food intake stimulation by RLN3 compared to RXFP3-A2 may relate to activation of both orexigenic and anorexigenic circuits by RLN3.
Publisher: S. Karger AG
Date: 17-12-2020
DOI: 10.1159/000513830
Abstract: b i Introduction: /i /b Food intake varies during the ovarian hormone/estrous cycle in humans and rodents, an effect mediated mainly by estradiol. A potential mediator of the central anorectic effects of estradiol is the neuropeptide relaxin-3 (RLN3) synthetized in the nucleus incertus (NI) and acting via the relaxin family peptide-3 receptor (RXFP3). b i Methods: /i /b We investigated the relationship between RLN3/RXFP3 signaling and feeding behavior across the female rat estrous cycle. We used in situ hybridization to investigate expression patterns of i Rln3 /i mRNA in NI and i Rxfp3 /i mRNA in the hypothalamic paraventricular nucleus (PVN), lateral hypothalamic area (LHA), medial preoptic area (MPA), and bed nucleus of the stria terminalis (BNST), across the estrous cycle. We identified expression of estrogen receptors (ERs) in the NI using droplet digital PCR and assessed the electrophysiological responsiveness of NI neurons to estradiol in brain slices. b i Results: /i /b i Rln3 /i mRNA reached the lowest levels in the NI pars compacta during proestrus. i Rxfp3 /i mRNA levels varied across the estrous cycle in a region-specific manner, with changes observed in the perifornical LHA, magnocellular PVN, dorsal BNST, and MPA, but not in the parvocellular PVN or lateral LHA. G protein-coupled estrogen receptor 1 ( i Gper1 /i ) mRNA was the most abundant ER transcript in the NI. Estradiol inhibited 33% of type 1 NI neurons, including RLN3-positive cells. b i Conclusion: /i /b These findings demonstrate that the RLN3/RXFP3 system is modulated by the estrous cycle, and although further studies are required to better elucidate the cellular and molecular mechanisms of estradiol signaling, current results implicate the involvement of the RLN3/RXFP3 system in food intake fluctuations observed across the estrous cycle in female rats.
Publisher: Elsevier BV
Date: 03-2016
DOI: 10.1016/J.NEUROPHARM.2015.11.014
Abstract: Binge eating is frequently stimulated by stress. The neuropeptide relaxin-3 (RLN3) and its native receptor RXFP3 are implicated in stress and appetitive behaviors. We investigated the dynamics of the central RLN3/RXFP3 system in a newly established model of stress-induced binge eating. Female Sprague-Dawley rats were subjected to unpredictable intermittent 1-h access to 10% sucrose. When sucrose intake stabilized, rats were assessed for consistency of higher or lower sucrose intake in response to three unpredictable episodes of foot-shock stress and assigned as binge-like eating prone (BEP) or binge-like eating resistant (BER). BEP rats displayed elevated consumption of sucrose under non-stressful conditions (30% > BER) and an additional marked increase in sucrose intake (60% > BER) in response to stress. Conversely, sucrose intake in BER rats was unaltered by stress. Chow intake was similar in both phenotypes on 'non-stress' days, but was significantly reduced by stress in BER, but not BEP, rats. After stress, BEP, but not BER, rats displayed a significant increase in RLN3 mRNA levels in the nucleus incertus. In addition, in response to stress, BEP, but not BER, rats had increased RXFP3 mRNA levels in the paraventricular and supraoptic nuclei of the hypothalamus. Intracerebroventricular administration of a selective RXFP3 antagonist, R3(B1-22)R, blocked the stress-induced increase in sucrose intake in BEP rats and had no effect on sucrose intake in BER rats. These results provide important evidence for a role of the central RLN3/RXFP3 system in the regulation of stress-induced binge eating in rats, and have therapeutic implications for eating disorders.
Publisher: Cold Spring Harbor Laboratory
Date: 16-08-2023
DOI: 10.1101/2023.08.14.553279
Abstract: Women have a higher incidence of Alzheimer’s disease (AD), even after adjusting for increased longevity. Thus, there is an urgent need to identify the molecular networks that underpin the sex-associated risk of AD. Recent efforts have identified PIN1 as a key regulator of tau phosphorylation signaling pathway . Pin1 is the only gene, to date, that when deleted can cause both tau and Aβ-related pathologies in an age-dependent manner. We analyzed multiple brain transcriptomic datasets focusing on sex differences in PIN1 mRNA levels, in an aging and AD cohort, which revealed reduced PIN1 levels driven by females. Then, we validated this observation in an independent dataset (ROS/MAP) which also revealed that PIN1 is negatively correlated with multiregional neurofibrillary tangle density and global cognitive function, in females only. Additional analysis revealed a decrease in PIN1 in subjects with mild cognitive impairment (MCI) compared with aged in iduals, again, driven predominantly by female subjects. Our results show that while both male and female AD patients show decreased PIN1 expression, changes occur before the onset of clinical symptoms of AD in females and correlate to early events associated with AD risk (e.g., synaptic dysfunction). These changes are specific to neurons, and may be a potential prognostic marker to assess AD risk in the aging population and even more so in AD females with increased risk of AD.
Publisher: Wiley
Date: 18-08-2015
DOI: 10.1111/GBB.12236
Abstract: Relaxin-3 (RLN3) is an orexigenic neuropeptide that produces sex-specific effects on food intake by stronger stimulation of feeding in female compared with male rats. This study determined which hypothalamic nuclei and associated neuropeptides may be involved in the sex-specific orexigenic effects of RLN3. Relaxin-3 (800 pmol) or vehicle was injected into the lateral ventricle of female and male rats. Food and water intake were measured after the first injection, and rats were euthanized after the second injection to determine the mRNA expression of the hypothalamic neuropeptides. Food but not water intake showed sex-specific effects of RLN3. Stimulation of food intake by RLN3 was significantly higher in female than in male rats. No effect of RLN3 injection was found on c-fos mRNA expression in the arcuate, dorsomedial and ventromedial hypothalamic nuclei. Increased c-fos mRNA expression was observed in the paraventricular hypothalamic nucleus (PVN) in both sexes and in the lateral hypothalamic area (LHA) in female rats. Relaxin-3 injections led to a sex-nonspecific increase in the expression of oxytocin mRNA in the magnocellular PVN. Conversely, RLN3-induced expression of anorexigenic neuropeptide arginine vasopressin (AVP) was significantly higher in the parvocellular PVN in male compared with female rats. Finally, RLN3 administration significantly increased the expression of orexin (ORX) mRNA in the LHA in female but not in male rats. Stronger expression of anorexigenic AVP in the PVN in male rats and increased expression of ORX in the LHA in female rats may contribute to stronger orexigenic effects of RLN3 in female rats compared with male rats.
Publisher: Springer Science and Business Media LLC
Date: 27-02-2018
Publisher: Elsevier BV
Date: 02-2023
Publisher: Cold Spring Harbor Laboratory
Date: 09-09-2023
Publisher: Wiley
Date: 27-02-2017
DOI: 10.1113/JP273787
Publisher: Wiley
Date: 13-07-2017
DOI: 10.1111/BPH.13530
Location: No location found
Location: Australia
Start Date: 2018
End Date: 2018
Funder: Mitacs
View Funded ActivityStart Date: 2017
End Date: 2019
Funder: Fonds de Recherche du Québec - Santé
View Funded ActivityStart Date: 2017
End Date: 2018
Funder: Erasmus+
View Funded ActivityStart Date: 2016
End Date: 2016
Funder: Fondation Institut Universitaire de Cardiologie et de Pneumologie de Québec
View Funded ActivityStart Date: 2016
End Date: 2017
Funder: Caisses Desjardins / Institut universitaire de cardiologie et de pneumologie de quebec
View Funded ActivityStart Date: 2016
End Date: 2017
Funder: Université Laval
View Funded ActivityStart Date: 2022
End Date: 2024
Funder: Alzheimer's Association
View Funded Activity