Dataset Information

Activation of the medial preoptic area (MPOA) ameliorates loss of maternal behavior in a Shank2 mouse model for autism.

ABSTRACT: Impairments in social relationships and awareness are features observed in autism spectrum disorders (ASDs). However, the underlying mechanisms remain poorly understood. Shank2 is a high-confidence ASD candidate gene and localizes primarily to postsynaptic densities (PSDs) of excitatory synapses in the central nervous system (CNS). We show here that loss of Shank2 in mice leads to a lack of social attachment and bonding behavior towards pubs independent of hormonal, cognitive, or sensitive deficits. Shank2^-/- mice display functional changes in nuclei of the social attachment circuit that were most prominent in the medial preoptic area (MPOA) of the hypothalamus. Selective enhancement of MPOA activity by DREADD technology re-established social bonding behavior in Shank2^-/- mice, providing evidence that the identified circuit might be crucial for explaining how social deficits in ASD can arise.

SUBMITTER: Grabrucker S

PROVIDER: S-EPMC7917557 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Activation of the medial preoptic area (MPOA) ameliorates loss of maternal behavior in a Shank2 mouse model for autism.

Grabrucker Stefanie S Pagano Jessica J Schweizer Johanna J Urrutia-Ruiz Carolina C Schön Michael M Thome Kevin K Ehret Günter G Grabrucker Andreas M AM Zhang Rong R Hengerer Bastian B Bockmann Jürgen J Verpelli Chiara C Sala Carlo C Boeckers Tobias M TM

The EMBO journal 20210125 5

Impairments in social relationships and awareness are features observed in autism spectrum disorders (ASDs). However, the underlying mechanisms remain poorly understood. Shank2 is a high-confidence ASD candidate gene and localizes primarily to postsynaptic densities (PSDs) of excitatory synapses in the central nervous system (CNS). We show here that loss of Shank2 in mice leads to a lack of social attachment and bonding behavior towards pubs independent of hormonal, cognitive, or sensitive defic ...[more]

PMID: 33491217

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Project description:The mother-child relationship is the most fundamental social bond in mammals, and previous studies indicate that the medial preoptic area (MPOA) contributes to this increase in sociability. It is possible that the same genes that lead to elevated sociability in one condition (the maternal state) might also be dysregulated in some disorders with social deficits (e.g. autism). In this study, we examined whether there was enrichment (greater than chance overlap) for social deficit disorder related genes in MPOA microarray results between virgin and postpartum female mice. We utilized microarrays to assess large scale gene expression changes in the MPOA of virgin and postpartum mice. The Modular Single Set Enrichment Test (MSET) was used to determine if mental health disorder related genes were enriched in significant microarray results. Additional resources, such as ToppCluster, NIH DAVID, and weighted co-expression network analysis (WGCNA) were used to analyze enrichment for specific gene clusters or indirect relationships between significant genes of interest. Finally, a subset of microarray results was validated using quantitative PCR.Significant postpartum MPOA microarray results were enriched for multiple disorders that include social deficits, including autism, bipolar disorder, depression, and schizophrenia. Together, 98 autism-related genes were identified from the significant microarray results. Further, ToppCluser and NIH DAVID identified a large number of postpartum genes related to ion channel activity and CNS development, and also suggested a role for microRNAs in regulating maternal gene expression. WGCNA identified a module of genes associated with the postpartum phenotype, and identified indirect links between transcription factors and other genes of interest.The transition to the maternal state involves great CNS plasticity and increased sociability. We identified multiple novel genes that overlap between the postpartum MPOA (high sociability) and mental health disorders with low sociability. Thus, the activity or interactions of the same genes may be altering social behaviors in different directions in different conditions. Maternity also involves elevated risks for disorders, including depression, psychosis, and BPD, so identification of maternal genes common to these disorders may provide insights into the elevated vulnerability of the maternal brain.

Dataset Information

Activation of the medial preoptic area (MPOA) ameliorates loss of maternal behavior in a Shank2 mouse model for autism.

Publications

Activation of the medial preoptic area (MPOA) ameliorates loss of maternal behavior in a Shank2 mouse model for autism.

Similar Datasets

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