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      Sexually dimorphic effects of a prenatal immune challenge on social play and vasopressin expression in juvenile rats

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          Abstract

          Background

          Infectious diseases and inflammation during pregnancy increase the offspring’s risk for behavioral disorders. However, how immune stress affects neural circuitry during development is not well known. We tested whether a prenatal immune challenge interferes with the development of social play and with neural circuits implicated in social behavior.

          Methods

          Pregnant rats were given intraperitoneal injections of the bacterial endotoxin lipopolysaccharide (LPS – 100 μg /kg) or saline on the 15th day of pregnancy. Offspring were tested for social play behaviors between postnatal days 26–40. Brains were harvested on postnatal day 45 and processed for arginine vasopressin (AVP) mRNA in situ hybridization.

          Results

          In males, LPS treatment reduced the frequency of juvenile play behavior and reduced AVP mRNA expression in the medial amygdala and bed nucleus of the stria terminalis. These effects were not found in females. LPS treatment did not change AVP mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, or supraoptic nucleus of either sex, nor did it affect the sex difference in the size of the sexually dimorphic nucleus of the preoptic area.

          Conclusions

          Given AVP’s central role in regulating social behavior, the sexually dimorphic effects of prenatal LPS treatment on male AVP mRNA expression may contribute to the sexually dimorphic effect of LPS on male social play and may, therefore, increase understanding of factors that contribute to sex differences in social psychopathology.

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          Most cited references53

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          Oxytocin, vasopressin, and the neurogenetics of sociality.

          There is growing evidence that the neuropeptides oxytocin and vasopressin modulate complex social behavior and social cognition. These ancient neuropeptides display a marked conservation in gene structure and expression, yet diversity in the genetic regulation of their receptors seems to underlie natural variation in social behavior, both between and within species. Human studies are beginning to explore the roles of these neuropeptides in social cognition and behavior and suggest that variation in the genes encoding their receptors may contribute to variation in human social behavior by altering brain function. Understanding the neurobiology and neurogenetics of social cognition and behavior has important implications, both clinically and for society.
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            Sex differences in schizophrenia.

            Evidence suggests sex differences in schizophrenia reflect differences in both neurodevelopmental processes and social effects on disease risk and course. Male:female incidence approximates 1.4:1 but at older onset women predominate. Prevalence differences appear smaller. Men have poorer premorbid adjustment and present with worse negative and less depressive symptoms than women, which may explain their worse medium term outcome according to a range of measures. Substance abuse is a predominantly male activity in this group, as elsewhere. Findings of sex differences in brain morphology are inconsistent but occur in areas that normally show sexual dimorphism, implying that the same factors are important drivers of sex differences in both normal neurodevelopmental processes and those associated with schizophrenia. There are sex differences in antipsychotic responses but sex-specific endocrine effects on illness and response to antipsychotics are potentially complex. Oestrogen's role as an adjunctive medication is not yet clear due to methodological differences between the few randomized controlled trials. Services that are sensitive to differences in gender can better meet their patients' specific needs and potentially improve outcome.
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              Maternal infection and immune involvement in autism.

              Recent studies have highlighted a connection between infection during pregnancy and the increased risk of autism in the offspring. Parallel studies of cerebral spinal fluid, blood and postmortem brains reveal an ongoing, hyper-responsive inflammatory-like state in many young as well as adult autism subjects. There are also indications of gastrointestinal problems in at least a subset of autistic children. Work on the maternal infection risk factor using animal models indicates that aspects of brain and peripheral immune dysregulation can begin during fetal development and continue through adulthood. The offspring of infected or immune-activated dams also display cardinal behavioral features of autism, as well as neuropathology consistent with that seen in human autism. These rodent models are proving useful for the study of pathogenesis and gene-environment interactions as well as for the exploration of potential therapeutic strategies. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Biol Sex Differ
                Biol Sex Differ
                Biology of Sex Differences
                BioMed Central
                2042-6410
                2012
                14 June 2012
                : 3
                : 15
                Affiliations
                [1 ]Center for Neuroendocrine Studies and Department of Psychology, University of Massachusetts, Amherst, MA, 01003, USA
                [2 ]Department of Psychology, Boston College, Chestnut Hill, MA, 02467, USA
                Article
                2042-6410-3-15
                10.1186/2042-6410-3-15
                3420237
                22697211
                cb34a392-7599-4675-acdd-16a242537a4c
                Copyright ©2012 Taylor et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 31 January 2012
                : 14 June 2012
                Categories
                Research

                Human biology
                play behavior,bed nucleus of the stria terminalis,development,sex differences,lipopolysaccharides,sdn-poa,medial amygdaloid nucleus,prenatal

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