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Mechanisms behind psychosocial stress-induced spontaneous colitis in male mice
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Abstracts / Brain, Behavior, and Immunity 24 (2010) S1–S71
characterized. LPS stimulation caused fast transient rises of intracellular calcium concentration in 17% of neurons, 9% of astrocytes and less than 5% of microglial cells investigated. LPS additionally led to enhanced expression of TNF and IL-1 exclusively in microglial cells and a time-dependent release of TNF and IL-6 from OVLT microcultures. TNF evoked calcium signals in 11% of neurons, 22% of astrocytes and 5% of microglial cells. A considerable population of neurons (11%) but only few astrocytes and microglial cells responded to IL-6, whereas 8% of microglial cells and 3% of astrocytes and neurons were activated by IL-1. The demonstration of direct cellular responses of OVLT-intrinsic cells to stimulations with LPS or cytokines reinforces the suggested role of this brain structure as a true sensor for circulating pyrogens. doi:10.1016/j.bbi.2010.07.004
Abstract # 195 The immune system regulates sensorimotor gating activity trough expression of Kisspeptin M. Cardon a, N. Ron-Harel a, G.M. Lewitus a,b, M. Schwartz a a
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel, Rehovot, Israel b Department of Neurobiology and Department of Neurosurgery, Centre for Research in neuroscience, The McGill University Health Center, Montreal, QC, Canada
We previously demonstrated that along with profound behavioural (anxiety) and neuroendocrine (HPA-axis) changes, chronic subordinate colony (CSC) housing causes spontaneous colitis. Aim of the present study was to identify the underlying mechanisms focussing on both early (10 h of CSC) changes in epithelial barrier and immune functions before colitis development. Here, Taqman PCR revealed no differences in antimicrobial peptide expression in colonic tissue following 10 h of CSC. However, in addition to a decrease in both proliferation and apoptosis of epithelial cells of CSC compared with non-stressed control mice, suggesting an impairment of epithelial cell renewal, a significantly decreased in vitro IgA secretion from isolated lamina propria mononuclear cells (LPMCs) was found following 10 h of CSC. Interestingly, this was accompanied by an increased bacterial translocation. Furthermore, 10 h of CSC housing caused immuno-suppression within the colonic tissue, indicated by a reduced secretion of TNF, IFN-gamma, IL-6, and IL17 from stimulated LPMCs. In addition, immunohistochemistry followed by computerized analysis revealed a significant decrease in the number of CD3, CD4, F4/80, and CD11c positive cells in the colonic tissue of CSC compared with control mice. These data suggest that psychosocial stress has severe effects both on intestinal immune and intestinal barrier functions resulting in increased bacterial translocation. The co-incidence of both may finally lead to the observed intestinal inflammation beginning after two weeks of CSC housing. doi:10.1016/j.bbi.2010.07.006
Abstract # 197 The immune system role in several psychiatric diseases such as schizophrenia, obsessive–compulsive disorder (OCD), Autistic disorder (AD), Tourette’s syndrome and attention deficit hyperactivity disorder (ADHD) has been studied for decades. The patophysiology of all of these disorders involves abnormal sensorimotor gating. Yet, the direct effect of the immune system on sensorimotor gating has been hardly studied. Here we will show that sensorimotor gating measured by prepulse inhibition (PPI) is tightly regulated by the immune system. Immune deficiency (SCID) mice had abnormal PPI that could be reversed by immune reconstitutions. In addition, manipulations of autoimmune responses resulted in abnormal PPI. The immune regulation on PPI is mediated by the endogenous peptide Kisspeptins, produced by the Kiss1 gene, which has an important role in initiating sex hormones secretions. Peripheral administration of the Kisspeptin-derived peptide Kp-10 could overcome abnormal PPI caused by immune deficiency in mice. Furthermore, Kp-10 elevates PPI levels in wild type mice. Our results show the role of the immune system in enabling proper sensorimotor gating through Kisspeptin expression regulation. doi:10.1016/j.bbi.2010.07.005
Abstract # 196 Mechanisms behind psychosocial stress-induced spontaneous colitis in male mice S.O. Reber a, I.D. Neumann c, F. Obermeier b a Chronic Stress Group, Department of Behavioural and Molecular Neuroendocrinology, University of Regensburg, Regensburg 9351, Germany b Department of Internal Medicine I, University of Regensburg, Germany c Department of Behavioural and Molecular Neuroendocrinology, University of Regensburg, Germany
A role for central IL-1beta in the suppression of locomotor activity induced the by the beta2-adrenoceptor agonist clenbuterol? K.J. Ryan, K.M. Ryan, E.W. Griffin, E.N. McNamee, A. Harkin, T.J. Connor Trinity College Institute of Neuroscience, Department of Physiology, Trinity College, Dublin 2, United States of America We have recently demonstrated that the brain permeable beta2adrenoceptor agonist clenbuterol selectively increases IL-1beta expression in the CNS (cortex, hippocampus and hypothalamus) without inducing expression of other inflammatory cytokines including TNF-alpha, IL-6 and IFN-gamma. This clenbuterol-induced increase in central IL-1beta expression is paralleled by a reduction in locomotor activity. As IL-1beta is known to induce sickness behaviours including the suppression of locomotor activity we examined the role of central IL-1beta expression in the suppressive effect of clenbuterol on locomotor activity in rats. We demonstrate that whilst the anti-inflammatory agent dexamethasone completely blocked induction of IL-1beta by clenbuterol, it failed to alter the suppressive action of clenbuterol on locomotor activity, indicating that central IL-1beta does not mediate the suppressive effect of clenbuterol on locomotor activity. In support of this finding, the peripherally acting beta-adrenoceptor antagonist, nadolol, which fails to inhibit clenbuterol-induced central IL-1beta expression completely blocked the suppressive effect of clenbuterol on locomotor activity. In contrast, treatment with propranolol, a beta-adrenoceptor antagonist that can penetrate the brain, blocked both the induction of central IL-1beta and suppression of locomotor activity induced by clenbuterol. These data indicate that peripheral betaadrenoceptors mediate the suppression of locomotor activity induced by clenbuterol, and that this suppression of locomotor activity occurs independent of its ability of induce central IL-1beta expression. It is suggested that the suppression of locomotor activity
Abstracts / Brain, Behavior, and Immunity 24 (2010) S1–S71
characterized. LPS stimulation caused fast transient rises of intracellular calcium concentration in 17% of neurons, 9% of astrocytes and less than 5% of microglial cells investigated. LPS additionally led to enhanced expression of TNF and IL-1 exclusively in microglial cells and a time-dependent release of TNF and IL-6 from OVLT microcultures. TNF evoked calcium signals in 11% of neurons, 22% of astrocytes and 5% of microglial cells. A considerable population of neurons (11%) but only few astrocytes and microglial cells responded to IL-6, whereas 8% of microglial cells and 3% of astrocytes and neurons were activated by IL-1. The demonstration of direct cellular responses of OVLT-intrinsic cells to stimulations with LPS or cytokines reinforces the suggested role of this brain structure as a true sensor for circulating pyrogens. doi:10.1016/j.bbi.2010.07.004
Abstract # 195 The immune system regulates sensorimotor gating activity trough expression of Kisspeptin M. Cardon a, N. Ron-Harel a, G.M. Lewitus a,b, M. Schwartz a a
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel, Rehovot, Israel b Department of Neurobiology and Department of Neurosurgery, Centre for Research in neuroscience, The McGill University Health Center, Montreal, QC, Canada
We previously demonstrated that along with profound behavioural (anxiety) and neuroendocrine (HPA-axis) changes, chronic subordinate colony (CSC) housing causes spontaneous colitis. Aim of the present study was to identify the underlying mechanisms focussing on both early (10 h of CSC) changes in epithelial barrier and immune functions before colitis development. Here, Taqman PCR revealed no differences in antimicrobial peptide expression in colonic tissue following 10 h of CSC. However, in addition to a decrease in both proliferation and apoptosis of epithelial cells of CSC compared with non-stressed control mice, suggesting an impairment of epithelial cell renewal, a significantly decreased in vitro IgA secretion from isolated lamina propria mononuclear cells (LPMCs) was found following 10 h of CSC. Interestingly, this was accompanied by an increased bacterial translocation. Furthermore, 10 h of CSC housing caused immuno-suppression within the colonic tissue, indicated by a reduced secretion of TNF, IFN-gamma, IL-6, and IL17 from stimulated LPMCs. In addition, immunohistochemistry followed by computerized analysis revealed a significant decrease in the number of CD3, CD4, F4/80, and CD11c positive cells in the colonic tissue of CSC compared with control mice. These data suggest that psychosocial stress has severe effects both on intestinal immune and intestinal barrier functions resulting in increased bacterial translocation. The co-incidence of both may finally lead to the observed intestinal inflammation beginning after two weeks of CSC housing. doi:10.1016/j.bbi.2010.07.006
Abstract # 197 The immune system role in several psychiatric diseases such as schizophrenia, obsessive–compulsive disorder (OCD), Autistic disorder (AD), Tourette’s syndrome and attention deficit hyperactivity disorder (ADHD) has been studied for decades. The patophysiology of all of these disorders involves abnormal sensorimotor gating. Yet, the direct effect of the immune system on sensorimotor gating has been hardly studied. Here we will show that sensorimotor gating measured by prepulse inhibition (PPI) is tightly regulated by the immune system. Immune deficiency (SCID) mice had abnormal PPI that could be reversed by immune reconstitutions. In addition, manipulations of autoimmune responses resulted in abnormal PPI. The immune regulation on PPI is mediated by the endogenous peptide Kisspeptins, produced by the Kiss1 gene, which has an important role in initiating sex hormones secretions. Peripheral administration of the Kisspeptin-derived peptide Kp-10 could overcome abnormal PPI caused by immune deficiency in mice. Furthermore, Kp-10 elevates PPI levels in wild type mice. Our results show the role of the immune system in enabling proper sensorimotor gating through Kisspeptin expression regulation. doi:10.1016/j.bbi.2010.07.005
Abstract # 196 Mechanisms behind psychosocial stress-induced spontaneous colitis in male mice S.O. Reber a, I.D. Neumann c, F. Obermeier b a Chronic Stress Group, Department of Behavioural and Molecular Neuroendocrinology, University of Regensburg, Regensburg 9351, Germany b Department of Internal Medicine I, University of Regensburg, Germany c Department of Behavioural and Molecular Neuroendocrinology, University of Regensburg, Germany
A role for central IL-1beta in the suppression of locomotor activity induced the by the beta2-adrenoceptor agonist clenbuterol? K.J. Ryan, K.M. Ryan, E.W. Griffin, E.N. McNamee, A. Harkin, T.J. Connor Trinity College Institute of Neuroscience, Department of Physiology, Trinity College, Dublin 2, United States of America We have recently demonstrated that the brain permeable beta2adrenoceptor agonist clenbuterol selectively increases IL-1beta expression in the CNS (cortex, hippocampus and hypothalamus) without inducing expression of other inflammatory cytokines including TNF-alpha, IL-6 and IFN-gamma. This clenbuterol-induced increase in central IL-1beta expression is paralleled by a reduction in locomotor activity. As IL-1beta is known to induce sickness behaviours including the suppression of locomotor activity we examined the role of central IL-1beta expression in the suppressive effect of clenbuterol on locomotor activity in rats. We demonstrate that whilst the anti-inflammatory agent dexamethasone completely blocked induction of IL-1beta by clenbuterol, it failed to alter the suppressive action of clenbuterol on locomotor activity, indicating that central IL-1beta does not mediate the suppressive effect of clenbuterol on locomotor activity. In support of this finding, the peripherally acting beta-adrenoceptor antagonist, nadolol, which fails to inhibit clenbuterol-induced central IL-1beta expression completely blocked the suppressive effect of clenbuterol on locomotor activity. In contrast, treatment with propranolol, a beta-adrenoceptor antagonist that can penetrate the brain, blocked both the induction of central IL-1beta and suppression of locomotor activity induced by clenbuterol. These data indicate that peripheral betaadrenoceptors mediate the suppression of locomotor activity induced by clenbuterol, and that this suppression of locomotor activity occurs independent of its ability of induce central IL-1beta expression. It is suggested that the suppression of locomotor activity