Unknown,Transcriptomics,Genomics,Proteomics

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Unexpected role of interferon-g in regulating neuronal connectivity and social behavior

ABSTRACT: We identified an enrichment in IFN-gamma dependent genes in the prefrontal cortex of group housed mice compared to single housed mice. Mice were house either grouped or single for 6 days. Mice were euthanized and brains were removed. The prefrontal cortex was disected and prepared for RNA-seq analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Christopher Overall

PROVIDER: E-GEOD-81783 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour.

Filiano Anthony J AJ Xu Yang Y Tustison Nicholas J NJ Marsh Rachel L RL Baker Wendy W Smirnov Igor I Overall Christopher C CC Gadani Sachin P SP Turner Stephen D SD Weng Zhiping Z Peerzade Sayeda Najamussahar SN Chen Hao H Lee Kevin S KS Scott Michael M MM Beenhakker Mark P MP Litvak Vladimir V Kipnis Jonathan J

Nature 20160713 7612

Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory. Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions. Associ ...[more]

PMID: 27409813

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Project description:Adolescence is a critical period in cognitive and emotional development, characterized by high levels of social interaction and increases in risk-taking behavior including binge drinking. Adolescent exposure to social stress and binge ethanol have individually been associated with the development of social, emotional, and cognitive deficits, as well as increased risk for alcohol use disorder. Disruption of cortical development by early life social stress and/or binge drinking may partly underlie these enduring emotional, cognitive, and behavioral effects. The study goal is to implement a novel neighbor housing environment to identify the effects of adolescent neighbor housing and/or binge ethanol drinking on (1) a battery of emotional and cognitive tasks (2) adult ethanol drinking behavior, and (3) the nucleus accumbens and prefrontal cortex transcriptome. Adolescent male and female C57BL/6J mice were single or neighbor housed with or without access to intermittent ethanol. One cohort underwent behavioral testing during adulthood to determine social preference, expression of anxiety-like behavior, cognitive performance, and patterns of ethanol intake. The second cohort was sacrificed in late adolescence and brain tissue was used for transcriptomics analysis. As adults, single housed mice displayed decreased social interaction, deficits in the novel object recognition task, and increased anxiety-like behavior, relative to neighbor-housed mice. There was no effect of housing condition on adolescent or adult ethanol consumption. Adolescent ethanol exposure did not alter adult ethanol intake. Transcriptomics analysis revealed that adolescent housing condition and ethanol exposure resulted in differential expression of genes related to synaptic plasticity in the nucleus accumbens and genes related to methylation, the extracellular matrix and inflammation in the prefrontal cortex. The behavioral results indicate that social interaction during adolescence via the neighbor housing model may protect against emotional, social, and cognitive deficits. In addition, the transcriptomics results suggest that these behavioral alterations may be mediated in part by dysregulation of transcription in the frontal cortex or the nucleus accumbens

Project description:The transition to motherhood involves CNS changes that modify sociability and affective state. However, these changes also put females at risk for postpartum depression and psychosis, which impairs parenting abilities and adversely affects children. Thus, changes in expression and interactions in a core subset of genes may be critical for emergence of a healthy maternal phenotype, but inappropriate changes of the same genes could put women at risk for postpartum disorders. This study evaluated microarray gene expression changes in medial prefrontal cortex (mPFC), a region implicated in both maternal behavior and psychiatric disorders. Postpartum mice were compared to virgin controls housed with females and isolated for identical durations. Using the Modular Single-set Enrichment Test (MSET), we found that the genetic landscape of maternal mPFC bears statistical similarity to gene databases associated with schizophrenia (5 of 5 sets) and bipolar disorder (BPD, 3 of 3 sets). In contrast to previous studies of maternal lateral septum and medial preoptic area, enrichment of autism and depression-linked genes was not significant (2 of 9 sets, 0 of 4 sets). Among genes linked to multiple disorders were fatty acid binding protein 7 (Fabp7), glutamate metabotropic receptor 3 (Grm3), platelet derived growth factor, beta polypeptide (Pdgfrb), and nuclear receptor subfamily 1, group D, member 1 (Nr1d1). RT-qPCR confirmed these gene changes as well as FMS-like tyrosine kinase 1 (Flt1) and proenkephalin (Penk). Systems-level methods revealed involvement of developmental gene networks in establishing the maternal phenotype and indirectly suggested a role for numerous microRNAs and transcription factors in mediating expression changes. Together, this study suggests that a subset of genes involved in shaping the healthy maternal brain may also be dysregulated in mental health disorders and put females at risk for postpartum psychosis with aspects of schizophrenia and BPD. In total, 10 total RNA samples derived from micropunched medial prefrontal cortex were used for microarray analysis: 5 samples from lactating maternal mice (maternal) and 5 samples from age-matched virgin mice (virgin). All samples are biological replicates.

Dataset Information

Unexpected role of interferon-g in regulating neuronal connectivity and social behavior

Publications

Unexpected role of interferon-γ in regulating neuronal connectivity and social behaviour.

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