ORCID Profile
0000-0002-4601-0189
Current Organisation
University of Tasmania
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: Elsevier BV
Date: 08-2007
DOI: 10.1016/J.NEULET.2007.07.012
Abstract: The complement anaphylatoxin C5a is a potent mediator of the innate immune response to infection. Recent evidence also reveals that C5a contributes to central nervous system effects in addition to its well-known peripheral functions. However, it is not known if C5a has a role in the activation of the hypothalamic-pituitary-adrenal (HPA) axis a critical cascade that exemplifies neuroimmune interactions between the periphery and the brain. In the present study we examined if systemic pre-treatment with a C5a receptor antagonist, PMX53, can affect lipopolysaccharide-induced (LPS 1 mg/kg, i.p.) activation of the HPA axis in the rat. Using Fos protein as a marker of neuronal activation, we found that systemic administration of PMX53 reduced the LPS-induced activation of paraventricular corticotropin-releasing factor (PVN CRF) and central amygdala cells. However, PMX53 did not alter LPS-induced responses in the bed nucleus of the stria terminalis, nucleus tractus solitarius and ventrolateral medulla. Our findings demonstrate that C5a may have a role in the activation of the HPA axis in response to systemic LPS.
Publisher: Springer US
Date: 2006
Publisher: American Physiological Society
Date: 12-2010
Abstract: Slow oscillations ( Hz) in neural activity occur during sleep and quiet wakefulness in both animals and humans. Single-cell recordings in cortical neurons have shown that these oscillations are driven by a combination of excitatory and inhibitory synaptic inputs. During up-states, although the ratio between them varies between cells, excitation and inhibition follow similar time courses. Neurons in the basolateral amygdala (BLA) also show slow oscillations between the resting membrane potential (down-state) and depolarized potentials (up-states). Delivery of footshock during the down-state fully reproduces up-states in these cells. Here we report that up-states in BLA principal neurons up-states begin with an excitatory drive that is rapidly (within ∼50 ms) overwhelmed by inhibitory input. This excess of inhibitory drive is short lasting (300–400 ms), after which up-states are maintained by a tight balance between excitation and inhibition. This initial large inhibitory input restricts action potential generation and reduces the firing frequency of these cells. These results indicate that, in contrast to cortical neurons, up-states in BLA neurons show an initial period of strong cortically driven feed-forward inhibition. For the remainder of the up-state, feedback inhibition then acts to balance excitatory input.
Publisher: Springer Science and Business Media LLC
Date: 15-09-2017
DOI: 10.1038/S41598-017-12115-X
Abstract: The central amygdala is critical for the acquisition and expression of fear memories. This region receives a dense innervation from brainstem noradrenergic cell groups and has a high level of α 2 -adrenoceptor expression. Using whole-cell electrophysiological recordings from rat brain slices, we characterise the role of pre-synaptic α 2 -adrenoceptor in modulating discrete inhibitory and excitatory connections within both the lateral and medial ision of the central amygdala. The selective α 2 -adrenoceptor agonist clonidine blocked the excitatory input from the pontine parabrachial neurons onto neurons of the lateral central amygdala. In addition, clonidine blocked inhibitory connections from the medial paracapsular intercalated cell mass onto both lateral and medial central amygdala neurons. To examine the behavioural consequence of α 2 -adrenoceptor-mediated inhibition of these inputs, we infused clonidine into the central amygdala prior to contextual fear-conditioning. In contrast to vehicle-infused rats, clonidine-infused animals displayed reduced levels of freezing 24 hours after training, despite showing no difference in freezing during the training session. These results reveal a role for α 2 -adrenoceptors within the central amygdala in the modulation of synaptic transmission and the formation of fear-memories. In addition, they provide further evidence for a role of the central amygdala in fear-memory formation.
Publisher: Informa UK Limited
Date: 2011
DOI: 10.3109/10253890109014752
Abstract: Physical stressors such as infection, inflammation and tissue injury elicit activation of the hypothalamic-pituitary-adrenal (HPA) axis. This response has significant implications for both immune and central nervous system function. Investigations in rats into the neural substrates responsible for HPA axis activation to an immune challenge have predominantly utilized an experimental paradigm involving the acute administration of the pro-inflammatory cytokine interleukin- 1β (IL-1β). It is well recognized that medial parvocellular corticotrophin-releasing factor cells of the paraventricular nucleus (mPVN CRF) are critical in generating HPA axis responses to an immune challenge but little is known about how peripheral immune signals can activate and/or modulate the mPVN CRF cells. Studies that have examined the afferent control of the mPVN CRF cell response to systemic IL-1β have centred largely on the inputs from brainstem catecholamine cells. However, other regulatory neuronal populations also merit attention and one such region is a component of the limbic system, the central nucleus of the amygdala (CeA). A large number of CeA cells are recruited following systemic IL-lβ administration and there is a significant body of work indicating that the CeA can influence HPA axis function. However, the contribution of the CeA to HPA axis responses to an immune challenge is only just beginning to be addressed. This review examines three aspects of HPA axis control by systemic IL-1β: (i) whether the CeA has a role in generating HPA axis responses to systemic IL-1β, (ii) the identity of the neural connections between the CeA and mPVN CRF cells that might be important to HPA axis responses and(iii) the mechanisms by which systemic IL-Iβ triggers the recruitment of CeA cells.
Publisher: The American Association of Immunologists
Date: 15-12-2008
DOI: 10.4049/JIMMUNOL.181.12.8727
Abstract: Complement activation products are elevated in the cerebrospinal fluid and spinal cord of patients with amyotrophic lateral sclerosis (ALS). In this study, we demonstrate complement system involvement in a rodent model of ALS (human SOD1G93A transgenic rats). With end-stage disease, SOD1G93A rats displayed marked deposition of C3/C3b, and a significant up-regulation of the C5aR in the lumbar spinal cord. This was associated with increased numbers of C5aR-positive astrocytes. However, expression of C5L2, the alternative receptor for C5a, was highest on motor neurons early in the disease process. To determine the contribution of C5a to the pathology displayed by this model of ALS, rats were administered an orally active, selective C5aR antagonist (PMX205 1 mg/kg/day, oral). Animals treated with PMX205 displayed a significant extension of survival time and a reduction in end-stage motor scores, as compared with vehicle-treated rats. PMX205-treated animals also displayed reduced levels of astroglial proliferation in the lumbar spinal cord. This study provides the first demonstration of an involvement of C5a in an ALS model and suggests that inhibitors of complement activation could be beneficial in the treatment of this neurodegenerative disease.
Publisher: Springer Science and Business Media LLC
Date: 2005
DOI: 10.1007/S00210-004-1005-7
Abstract: Tandospirone, an azapirone, is a selective serotonin(1A) (5-HT(1A)) receptor agonist. The effects of tandospirone on plasma hormones and on mitogen-activated protein (MAP) kinase activity in the brain of male rats were studied. Tandospirone produced a time- and dose-dependent increase in plasma levels of oxytocin, adrenocorticotropin (ACTH), corticosterone, and prolactin. The minimal dose of tandospirone that led to a significant elevation of plasma oxytocin, ACTH, and prolactin levels was 1.0 mg/kg (s.c.), while the minimal dose for corticosterone release was 3.0 mg/kg (s.c.). The ED(50) of tandospirone was 1.3 mg/kg for oxytocin, 1.2 mg/kg for ACTH, 3.0 mg/kg for corticosterone, and 0.24 mg/kg for prolactin. Pretreatment with the specific 5-HT(1A) receptor antagonist WAY 100,635 (0.3 mg/kg, s.c.) completely blocked the effects of tandospirone on plasma levels of oxytocin, ACTH, and corticosterone but shifted the dose-response curve for prolactin to the right. Tandospirone injection (10 mg/kg, s.c.) stimulated the MAP kinase signaling cascade, specifically the phosphorylation of p42/44 extracellular signal-regulated kinase (ERK). Western blot analysis revealed a significant increase in phosphorylated ERK (p-ERK) levels in the hypothalamic paraventricular nucleus (PVN) as well as the dorsal raphe nucleus 5 min following tandospirone injection. These increases were blocked by pretreatment with WAY 100,635 (0.3 mg/kg). The results are the first evidence that systemic 5-HT(1A) receptor agonist administration produces a rapid increase in p-ERK levels in vivo, providing further insight into the signaling mechanisms of the 5-HT(1A) receptor.
Publisher: Springer Science and Business Media LLC
Date: 02-07-2018
DOI: 10.1038/S41598-018-28321-0
Abstract: The two main sub- isions of the Central amygdala (CeA), the lateral-capsular (CeA-LC) and the medial (CeA-M), contain extensive networks of inhibitory interneurons. We have previously shown that activation of GABA B -receptors reduces excitatory transmission between axons of the pontine parabrachial nucleus and neurons of the CeA-LC by inhibiting glutamate release from presynaptic terminals 13 . Here we have characterised GABA B -receptor activation on other excitatory and inhibitory projections within the CeA. Using whole-cell, patch-cl recordings, we found that the GABA B -receptor agonist baclofen significantly reduced excitatory and inhibitory transmission from all tested inputs into the CeA-LC and CeA-M. In all but one of the inputs, reductions in transmission were accompanied by an increase in paired pulse ratio, indicating that presynaptic GABA B -receptors acted to reduce the release probability of synaptic vesicles. To examine the impact of GABA B -receptors in the CeA on contextual fear-conditioning, we infused baclofen into the CeA immediately prior to training. Compared to vehicle-infused rats, baclofen-infused rats displayed significantly less freezing both during the final stages of the training period and at test 24 hours later. The results of this study demonstrate that, by suppressing excitatory and inhibitory transmission, activation of presynaptic GABA B -receptors in the CeA inhibits the development of context conditioned fear.
Publisher: Elsevier BV
Date: 08-2003
DOI: 10.1016/S0306-4530(02)00065-3
Abstract: Apomorphine is a dopamine receptor agonist that was recently licensed for the treatment of erectile dysfunction. However, although sexual activity can be stressful, there has been little investigation into whether treatments for erectile dysfunction affect stress responses. We have examined whether a single dose of apomorphine, sufficient to produce penile erections (50 microg/kg, i.a.), can alter basal or stress-induced plasma ACTH levels, or activity of central pathways thought to control the hypothalamic-pituitary-adrenal axis in rats. An immune challenge (interleukin-1 beta, 1 microg/kg, i.a.) was used as a physical stressor while sound stress (100 dB white noise, 30 min) was used as a psychological stressor. Intravascular administration of apomorphine had no effect on basal ACTH levels but did substantially increase the number of Fos-positive amygdala and nucleus tractus solitarius catecholamine cells. Administration of apomorphine prior to immune challenge augmented the normal ACTH response to this stressor at 90 min and there was a corresponding increase in the number of Fos-positive paraventricular nucleus corticotropin-releasing factor cells, paraventricular nucleus oxytocin cells and nucleus tractus solitarius catecholamine cells. However, apomorphine treatment did not alter ACTH or Fos responses to sound stress. These data suggest that erection-inducing levels of apomorphine interfere with hypothalamic-pituitary-adrenal axis inhibitory feedback mechanisms in response to a physical stressor, but have no effect on the response to a psychological stressor. Consequently, it is likely that apomorphine acts on a hypothalamic-pituitary-adrenal axis control pathway that is unique to physical stressors. A candidate for this site of action is the nucleus tractus solitarius catecholamine cell population and, in particular, A2 noradrenergic neurons.
Publisher: Wiley
Date: 07-2006
Abstract: The complement system is thought to be involved in the pathogenesis of numerous neurological diseases, although its precise role remains controversial. In this study we used orally active C5a receptor antagonists (PMX53 and PMX205) developed in our laboratories in a rat model of 3-nitropropionic acid (3-NP) -induced Huntington's disease. Administration of the C5a antagonists (10 mg/kg/day, oral) either 48 h pre- or 48 h post-toxin significantly reduced body weight loss, anorexia, and behavioral and motor deficits associated with 3-NP intoxication. Striatal lesion size, apoptosis, neutrophil infiltration, and hemorrhage were also significantly reduced in C5a antagonist-treated rats. Immunohistochemical analysis demonstrated marked deposition of C3 and C9, and up-regulation of C5a receptors on neuronal cells at the time of lesion formation. Inhibition of prostaglandins or TNF-alpha with ibuprofen or infliximab had no effect in this model. The C5a antagonists did not affect 3-NP-induced cell death when added directly to rat striatal neuronal cultures, indicating a secondary mechanism of action in vivo. Our findings demonstrate for the first time that complement activation in the brain, particularly C5a, is a key event in the pathogenesis of this disease model, and suggest a future role for inhibitors of C5a in the treatment of neurodegenerative diseases.
Publisher: Informa UK Limited
Date: 2005
DOI: 10.1080/10253890500333817
Abstract: By most accounts the psychological stressor restraint produces a distinct pattern of neuronal activation in the brain. However, some evidence is incongruous with this pattern, leading us to propose that the restraint-induced pattern in the central nervous system might depend on the duration of restraint used. We therefore determined the pattern of neuronal activation (as indicated by the presence of Fos protein) seen in the paraventricular nucleus (PVN), bed nucleus of the stria terminalis, amygdala, locus coeruleus, nucleus tractus solitarius (NTS), ventrolateral medulla (VLM) and thoracic spinal cord of the rat in response to 0, 15, 30 or 60 min periods of restraint. We found that although a number of cell groups displayed a linear increase in activity with increasing durations of restraint (e.g. hypothalamic corticotrophin-releasing factor (CRF) cells, medial amygdala neurons and sympathetic preganglionic neurons of the thoracic spinal cord), a number of cell groups did not. For ex le, in the central amygdala restraint produced both a decrease in CRF cell activity and an increase in non-CRF cell activity. In the locus coeruleus, noradrenergic neurons did not display Fos in response to 15 min of restraint, but were significantly activated by 30 or 60 min restraint. After 30 or 60 min restraint a greater degree of activation of more rostral A1 noradrenergic neurons was observed compared with the pattern of A1 noradrenergic neurons in response to 15 min restraint. The results of this study demonstrate that restraint stress duration determines the amount and the pattern of neuronal activation seen in response to this psychological stressor.
Publisher: American Physiological Society
Date: 02-2020
Abstract: Oxytocin (OT) is a neuroactive peptide that influences the processing of fearful stimuli in the amygdala. In the central nucleus of the amygdala, the activation of OT receptors alters neural activity and ultimately suppresses the behavioral response to a fear conditioned stimulus. Receptors for OT are also found in the lateral amygdala (LA), and infusion of OT into the basolateral amygdala complex affects the formation and consolidation of fear memories. Yet, how OT receptor activation alters neurons and neural networks in the LA is unknown. In this study we used whole cell electrophysiological recordings to determine how OT-receptor activation changes synaptic transmission and synaptic plasticity in the LA of Sprague-Dawley rats. Our results demonstrate that OT-receptor activation results in a 200% increase in spontaneous inhibitory transmission in the LA that leads to the activation of presynaptic GABA B receptors. The activation of these receptors inhibits excitatory transmission in the LA, blocking long-term potentiation of cortical inputs onto LA neurons. Hence, this study provides the first demonstration that OT influences synaptic transmission and plasticity in the LA, revealing a mechanism that could explain how OT regulates the formation and consolidation of conditioned fear memories in the amygdala. NEW & NOTEWORTHY This study investigates modulation of synaptic transmission by oxytocin (OT) in the lateral amygdala (LA). We demonstrate that OT induces transient increases in spontaneous GABAergic transmission by activating interneurons in the basolateral amygdala. The resultant increase in GABA release in the LA activates presynaptic GABA B receptors on both inhibitory and excitatory inputs onto LA neurons, reducing release probability at these synapses. We subsequently demonstrate that OT modulates synaptic plasticity at cortical inputs to the LA.
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.PSYNEUEN.2018.06.006
Abstract: Oxytocin (OT) is a neuropeptide which influences the expression of social behavior and regulates its distribution according to the social context - OT is associated with increased pro-social effects in the absence of social threat and defensive aggression when threats are present. The present experiments investigated the effects of OT beyond that of social behavior by using a discriminative Pavlovian fear conditioning protocol with rats. In Experiment 1, an OT receptor agonist (TGOT) microinjected into the basolateral amygdala facilitated the discrimination between an auditory cue that signaled shock and another auditory cue that signaled the absence of shock. This TGOT-facilitated discrimination was replicated in a second experiment where the shocked and non-shocked auditory cues were accompanied by a common visual cue. Conditioned responding on probe trials of the auditory and visual elements indicated that TGOT administration produced a qualitative shift in the learning mechanisms underlying the discrimination between the two compounds. This was confirmed by comparisons between the present results and simulated predictions of elemental and configural associative learning models. Overall, the present findings demonstrate that the neuromodulatory effects of OT influence behavior outside of the social domain.
Publisher: Wiley
Date: 10-2001
DOI: 10.1046/J.0953-816X.2001.01733.X
Abstract: It has been hypothesized that the brain categorizes stressors and utilizes neural response pathways that vary in accordance with the assigned category. If this is true, stressors should elicit patterns of neuronal activation within the brain that are category-specific. Data from previous immediate-early gene expression mapping studies have hinted that this is the case, but interstudy differences in methodology render conclusions tenuous. In the present study, immunolabelling for the expression of c-fos was used as a marker of neuronal activity elicited in the rat brain by haemorrhage, immune challenge, noise, restraint and forced swim. All stressors elicited c-fos expression in 25-30% of hypothalamic paraventricular nucleus corticotrophin-releasing-factor cells, suggesting that these stimuli were of comparable strength, at least with regard to their ability to activate the hypothalamic-pituitary-adrenal axis. In the amygdala, haemorrhage and immune challenge both elicited c-fos expression in a large number of neurons in the central nucleus of the amygdala, whereas noise, restraint and forced swim primarily elicited recruitment of cells within the medial nucleus of the amygdala. In the medulla, all stressors recruited similar numbers of noradrenergic (A1 and A2) and adrenergic (C1 and C2) cells. However, haemorrhage and immune challenge elicited c-fos expression in subpopulations of A1 and A2 noradrenergic cells that were significantly more rostral than those recruited by noise, restraint or forced swim. The present data support the suggestion that the brain recognizes at least two major categories of stressor, which we have referred to as 'physical' and 'psychological'. Moreover, the present data suggest that the neural activation footprint that is left in the brain by stressors can be used to determine the category to which they have been assigned by the brain.
Publisher: Springer Science and Business Media LLC
Date: 12-01-2016
DOI: 10.1038/SREP19255
Abstract: The nocioceptive information carried by neurons of the pontine parabrachial nucleus to neurons of the lateral ision of the central amydala (CeA-L) is thought to contribute to the affective components of pain and is required for the formation of conditioned-fear memories. Importantly, excitatory transmission between parabrachial axon terminals and CeA-L neurons can be inhibited by a number of presynaptic receptors linked to Gi/o-type G-proteins, including α2-adrenoceptors and GABA B receptors. While the intracellular signalling pathway responsible for α2-adrenoceptor inhibition of synaptic transmission at this synapse is known, the mechanism by which GABA B receptors inhibits transmission has not been determined. The present study demonstrates that activation of presynaptic GABA B receptors reduces excitatory transmission between parabrachial axon terminals and CeA-L neurons by inhibiting N-type calcium channels. While the involvement of G βγ subunits in mediating the inhibitory effects of GABA B receptors on N-type calcium channels is unclear, this inhibition does not involve G βγ -independent activation of pp60C-src tyrosine kinase. The results of this study further enhance our understanding of the modulation of the excitatory input from parabrachial axon terminals to CeA-L neurons and indicate that presynaptic GABA B receptors at this synapse could be valuable therapeutic targets for the treatment of fear- and pain-related disorders.
Publisher: Springer Science and Business Media LLC
Date: 2009
Publisher: Society for Neuroscience
Date: 22-10-2008
DOI: 10.1523/JNEUROSCI.1796-08.2008
Abstract: Emotionally arousing events are particularly well remembered. This effect is known to result from the release of stress hormones and activation of β adrenoceptors in the amygdala. However, the underlying cellular mechanisms are not understood. Small conductance calcium-activated potassium (SK) channels are present at glutamatergic synapses where they limit synaptic transmission and plasticity. Here, we show that β adrenoceptor activation regulates synaptic SK channels in lateral amygdala pyramidal neurons, through activation of protein kinase A. We show that SK channels are constitutively recycled from the postsynaptic membrane and that activation of β adrenoceptors removes SK channels from excitatory synapses. This results in enhanced synaptic transmission and plasticity. Our findings demonstrate a novel mechanism by which β adrenoceptors control synaptic transmission and plasticity, through regulation of SK channel trafficking, and suggest that modulation of synaptic SK channels may contribute to β adrenoceptor-mediated potentiation of emotional memories.
Publisher: American Physiological Society
Date: 09-2009
Abstract: Slow oscillations ( Hz) in neural activity occur during sleep and quiet wakefulness in both animals and humans. Here we show that in urethan-anesthetized animals, neurons in the basolateral amygdala in vivo display a slow oscillation between resting membrane potential (down-state) and depolarized potentials (up-states) occurring at a frequency of ∼0.3 Hz. This oscillation is insensitive to the holding potential and continues unabated under voltage cl , indicating that up-states are synaptically driven. Somatosensory stimulation (footshock) delivered during the down-state evoked an all-or-none transition into an up-state. When delivered during down-states, footshocks triggered up-states and reset the phase of the neural oscillation, effectively synchronizing activity in the basolateral amygdala. This phase reset was reproduced by posterior thalamus stimulation, confirming that it was mediated by aversive sensory input. In contrast, a footshock delivered during the up-state was ineffective in stimulating BLA neurons. We conclude that oscillatory activity in the basolateral amygdala is driven by ensembles of cortical neurons. These ensembles gate the response of amygdala neurons to aversive stimulation in a state-dependent manner. Aversive stimulation is effective when the network is in the down-state but ineffective when the network is in an up-state.
Publisher: Cold Spring Harbor Laboratory
Date: 29-07-2020
DOI: 10.1101/2020.07.29.226555
Abstract: Genomic mutation of the virus may impact the viral adaptation to the local environment, their transmission, disease manifestation, and the effectiveness of existing treatment and vaccination. The objectives of this study were to characterize genomic variations, non-synonymous amino acid substitutions, especially in target proteins, mutation events per s les, mutation rate, and overall scenario of coronaviruses across the country. To investigate the genetic ersity, a total of 184 genomes of virus strains s led from different isions of Bangladesh with s ling dates between the 10th of May 2020 and the 27 th of June 2020 were analyzed. To date, a total of 634 mutations located along the entire genome resulting in non-synonymous 274 amino acid substitutions in 22 different proteins were detected with nucleotide mutation rate estimated to be 23.715 substitutions per year. The highest non-synonymous amino acid substitutions were observed at 48 different positions of the papain-like protease (nsp3). Although no mutations were found in nsp7, nsp9, nsp10, and nsp11, yet orf1ab accounts for 56% of total mutations. Among the structural proteins, the highest non-synonymous amino acid substitution (at 36 positions) observed in spike proteins, in which 9 unique locations were detected relative to the global strains, including 516E Q in the boundary of the ACE2 binding region. The most dominated variant G614 (95%) based in spike protein is circulating across the country with co-evolving other variants including L323 (94%) in RNA dependent RNA polymerase (RdRp), K203 (82%) and R204 (82%) in nucleocapsid, and F120 (78%) in NSP2. These variants are mostly seen as linked mutations and are part of a haplotype observed in Europe. Data suggest effective containment of clade G strains (4.8%) with sub-clusters GR 82.4%, and GH clade 6.4%. We have sequenced 137 and analyzed 184 whole-genomes sequences of SARS-CoV-2 strains from different isions of Bangladesh. A total of 634 mutation sites across the SARS-CoV-2 genome and 274 non-synonymous amino acid substitutions were detected. The mutation rate of SARS-CoV-2 estimated to be 23.715 nucleotide substitutions per year. Nine unique variants were detected based on non-anonymous amino acid substitutions in spike protein relative to the global SARS-CoV-2 strains.
Publisher: Wiley
Date: 24-10-2003
DOI: 10.1002/CNE.10918
Abstract: Systemic infection activates the hypothalamic-pituitary-adrenal (HPA) axis, and brainstem catecholamine cells have been shown to contribute to this response. However, recent work also suggests an important role for the central amygdala (CeA). Because direct connections between the CeA and the hypothalamic apex of the HPA axis are minimal, the present study investigated whether the bed nucleus of the stria terminalis (BNST) might act as a relay between them. This was done by using an animal model of acute systemic infection involving intravascular delivery of the proinflammatory cytokine interleukin-1beta (IL-1beta, 1 microg/kg). Unilateral ibotenic acid lesions encompassing the ventral BNST significantly reduced both IL-1beta-induced increases in Fos immunoreactivity in corticotropin-releasing factor (CRF) cells of the hypothalamic paraventricular nucleus (PVN) and corresponding increases in adrenocorticotropic hormone (ACTH) secretion. Similar lesions had no effect on CRF cell responses to physical restraint, suggesting that the effects of BNST lesions were not due to a nonspecific effect on stress responses. In further studies, we examined the functional connections between PVN, BNST, and CeA by combining retrograde tracing with mapping of IL-1beta-induced increases in Fos in BNST and CeA cells. In the case of the BNST, these studies showed that systemic IL-1beta administration recruits ventral BNST cells that project directly to the PVN. In the case of the CeA, the results obtained were consistent with an arrangement whereby lateral CeA cells recruited by systemic IL-1beta could regulate the activity of medial CeA cells projecting directly to the BNST. In conclusion, the present findings are consistent with the hypothesis that the BNST acts as a relay between the CeA and PVN, thereby contributing to CeA modulation of hypophysiotropic CRF cell responses to systemic administration of IL-1beta.
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.BRAINRES.2007.07.101
Abstract: Brain serotonin 1A (5-HT1A) receptors play an important role in mood disorders and can modulate various intracellular signaling mechanisms. We previously reported that systemic administration of either full or partial 5-HT1A agonists increases neuroendocrine responses and that tandospirone, an azapirone partial agonist, can activate (phosphorylate) extracellular signal-regulated kinase (ERK) in the hypothalamic paraventricular nucleus (PVN). In contrast, decreased levels of phosphoERK (pERK) have been reported in hippoc us following in vivo administration of either azapirone or aminotetralin 5-HT1A agonists, such as 8-hydroxy-2-dipropylaminotetralin (8-OH-DPAT). The present study investigated the time-dependent activation of MAP kinase in hypothalamus by (+)8-OH-DPAT to determine the regional differences and receptor specificity of the changes in pERK. Adult male rats received a systemic injection of (+)8-OH-DPAT (200 microg/kg, s.c.). The time-dependent changes in ERK activation were examined in hypothalamic nuclei as well as other brain regions associated with modulation of mood. (+)8-OH-DPAT produced a rapid increase (at 5 min) and transient return (at 15 min) of pERK levels in PVN and medial basal hypothalamus. In contrast, pERK levels in hippoc us were reduced at both 5 and 15 min after (+)8-OH-DPAT. Pretreatment with the 5-HT1A receptor-specific antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2-pyridinyl)cyclohexanecarboxamide (WAY100635) completely blocked the (+)8-OH-DPAT-mediated changes in pERK levels in PVN, medial basal hypothalamus, and hippoc us. No significant (+)8-OH-DPAT-induced changes in pERK were observed in dorsal raphe or amygdala. In conclusion, these results demonstrate that 8-OH-DPAT activation of MAP kinase signaling in vivo is a transient and region-specific phenomenon and in rat hypothalamus and hippoc us is mediated by 5-HT1A receptors.
Publisher: Wiley
Date: 04-2003
DOI: 10.1046/J.1460-9568.2003.02568.X
Abstract: Previous studies have shown that the medial prefrontal cortex can suppress the hypothalamic-pituitary-adrenal axis response to stress. However, this effect appears to vary with the type of stressor. Furthermore, the absence of direct projections between the medial prefrontal cortex and corticotropin-releasing factor cells at the apex of the hypothalamic-pituitary-adrenal axis suggest that other brain regions must act as a relay when this inhibitory mechanism is activated. In the present study, we first established that electrolytic lesions involving the prelimbic and infralimbic medial prefrontal cortex increased plasma adrenocorticotropic hormone levels seen in response to a physical stressor, the systemic delivery of interleukin-1beta. However, medial prefrontal cortex lesions did not alter plasma adrenocorticotropic hormone levels seen in response to a psychological stressor, noise. To identify brain regions that might mediate the effect of medial prefrontal cortex lesions on hypothalamic-pituitary-adrenal axis responses to systemic interleukin-1beta, we next mapped the effects of similar lesions on interleukin-1beta-induced Fos expression in regions previously shown to regulate the hypothalamic-pituitary-adrenal axis response to this stressor. It was found that medial prefrontal cortex lesions reduced the number of Fos-positive cells in the ventral aspect of the bed nucleus of the stria terminalis. However, the final experiment, which involved combining retrograde tracing with Fos immunolabelling, revealed that bed nucleus of the stria terminalis-projecting medial prefrontal cortex neurons were largely separate from medial prefrontal cortex neurons recruited by systemic interleukin-1beta, an outcome that is difficult to reconcile with a simple medial prefrontal cortex-bed nucleus of the stria terminalis-corticotropin-releasing factor cell control circuit.
Publisher: Irish College of Paramedics
Date: 10-12-2018
Abstract: strong em Introduction /em /strong Paramedics are mobile health care workers who respond to trauma and medical emergencies. Worldwide, paramedics exhibit disturbingly high rates of injury and illness with increased markers of poor health, such as obesity and hypertension, being common. The primary aim of this study was to explore the self-reported health status of paramedics in New South Wales, Australia, by gender and geographic rostering pattern and to compare it with that of the Australian general population. A secondary aim was to examine paramedics’ attitudes towards exercise. strong em Methods /em /strong In 2015, paramedics employed by NSW Ambulance were invited to complete a web-based survey which composed of the Medical Outcomes Survey Short Form 36 (SF-36), and measures of attitudes towards exercise. Demographic information and participants’ height and weight (for calculating Body Mass Index (BMI)) were also collected. Normative comparator data for the Australian general population (BMI and SF-36 scores) were sourced from the Household Income Labour Dynamics in Australia 2015 survey. strong em Results /em /strong Of the approximately 3,300 paramedics invited to participate, 747 completed the survey (507 male, 240 female). Mean age and mean years of service were 41.5 ±9.5 (SD) and 13.6 ±9.0 respectively. There were no differences in SF-36 scores except for the Vitality domain where males scored higher than females (p& .001), and regional paramedics had a higher General Health domain score than metropolitan paramedics (p& .05). Regional male paramedics had higher BMIs than their metropolitan counterparts (28.04 kg/m sup /sup ± 3.99 vs. 26.81 kg/m sup /sup ± 4.67, p = 0.001). Compared to the Australian population, paramedics scored higher in the Physical Function domain (p& .001) but lower in summary scores for mental and physical health (p& .001). Paramedics’ BMIs were slightly higher than the general population (27.10 ± 4.30 kg/m sup /sup vs.26.47 ±5.42, p& .001). Paramedics reported lack of time, family, lack of motivation and in regional postings: distance to fitness facilities and shift patterns as barriers to exercise. strong em Conclusions /em /strong Paramedics scored lower on the SF-36 than the general population, which can indicate a lower health-related quality of life. High BMI and low SF-36 scores may be related to a perceived inability to engage in regular exercise and the effects of shift work, especially in regional areas. Increasing BMI can be associated with the development of markers of poor health. Attention is needed to ensure that these essential health care providers are “fit for duty”. This survey should be repeated longitudinally to examine trends in the health status of paramedics. Nationally and internationally, ambulance management can and should foster innovative health promotion programs and paramedics themselves need to recognise and value good health.
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 02-03-2005
Abstract: Neuroendocrine responses to administration of serotonin releasing agents or 5-hydroxytryptamine (5-HT) 1A receptor agonists have been used as an index of serotonin receptor function in patients with depression and other mood disorders. However, the receptor population that mediates these responses has not been clearly identified. We tested the hypothesis that 5-HT1A receptors in the paraventricular nucleus of the hypothalamus (PVN) mediate the release of adrenocorticotropin hormone (ACTH) and oxytocin after administration of a selective 5-HT1A agonist in conscious rats. Low-dose infusion (1 nmol/100 nl/side) of the selective 5-HT1A antagonist, WAY100635 (WAY [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl) ethyl)-N-(2-pyridinyl)cyclohexanecarboxamidetrihydrochloride), into the PVN blocked the rise in ACTH and oxytocin stimulated by low-dose (30 nmol/kg) i.v. administration of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT 274 +/- 53 versus 70 +/- 20 pg/ml, P < 0.01 for ACTH and 10.7 +/- 3.4 versus 4.6 +/- 0.7 pg/ml, P < 0.05 for oxytocin after saline or WAY pretreatment, respectively). WAY did not influence the bradycardic effect of 8-OH-DPAT (-56 +/- 7 versus -54 +/- 6 beats per minute after saline or WAY). 8-OH-DPAT treatment also elicited locomotor activation followed by hind limb abduction and flat body posture. Surprisingly, WAY attenuated some aspects of locomotor activation and reduced the duration of hind limb abduction elicited by the agonist (5.1 +/- 0.9 versus 0.3 +/- 0.3 min for saline- or WAY-treated rats). These data indicate that 5-HT1A receptor stimulation in the PVN mediates the characteristic neuroendocrine response to serotonin agonist challenge. Moreover, they provide the first evidence that aspects of the behavioral serotonin syndrome are mediated by forebrain hypothalamic receptors.
Publisher: Springer Science and Business Media LLC
Date: 24-12-2004
DOI: 10.1007/S00213-004-2103-4
Abstract: Interactions among stress, serotonin 1A (5-HT(1A)) receptors, and the hypothalamic-pituitary-adrenocortical (HPA) system have been proposed to influence the development of depression in humans. The investigation of depression-relevant behaviors and physiological responses to environmental stressors in animal models of depression may provide valuable insight regarding these mechanisms. The purpose of these experiments was to investigate the interactions among central 5-HT(1A) receptors, endocrine function, and behavior in an animal model of depression, chronic mild stress (CMS). The current study examined behavioral responses to a pleasurable stimulus (sucrose), estrous cycle length (in female rats), and plasma hormone levels following systemic administration of a selective 5-HT(1A) receptor agonist [(+)8-hydroxy-N,N-dipropyl-2-aminotetralin hydrobromide (8-OH-DPAT) 40 mug/kg, s.c. administered 15 min prior to sacrifice], in male and female rats exposed to 4 weeks of CMS. Four weeks of CMS produced a reduction in the intake of 1% sucrose (anhedonia), as well as attenuated adrenocorticotropic hormone (ACTH) responses to 8-OH-DPAT in both male and female rats (22 and 18% lower than the control groups, respectively). Corticosterone and oxytocin responses to 8-OH-DPAT were not altered by exposure to CMS. In female rats, CMS induced a lengthening of the estrous cycle by approximately 40%. CMS produces minor HPA disruptions along with behavioral disruptions. Alterations in 5-HT(1A) receptor function in specific populations of neurons in the central nervous system may be associated with the CMS model. The current findings contribute to our understanding of the relations that stress and neuroendocrine function have to depressive disorders.
Publisher: IEEE
Date: 04-2013
Publisher: Public Library of Science (PLoS)
Date: 12-05-2016
Publisher: Elsevier BV
Date: 12-2007
DOI: 10.1016/J.NEURON.2007.10.022
Abstract: The lateral ision of the central amygdala (CeAL) is the target of ascending fibers from the pain-responsive and stress-responsive nuclei in the brainstem. We show that single fiber inputs from the nociceptive pontine parabrachial nucleus onto CeAL neurons form suprathreshold glutamatergic synapses with multiple release sites. Noradrenaline, acting at presynaptic alpha2 receptors, potently inhibits this synapse. This inhibition results from a decrease in the number of active release sites with no change in release probability. Introduction of a presynaptic scavenger of Gbetagamma subunits blocked the effects of noradrenaline, and botulinum toxin A reduced its effects, showing a direct action of betagamma subunits on the release machinery. These data illustrate a mechanism of presynaptic modulation where the output of a large multiple-release-site synapse is potently regulated by endogenously released noradrenaline and suggests that the CeA may be a target for the central nociceptive actions of noradrenaline.
No related grants have been discovered for James Crane.