Sexual dimorphism in the social behaviour of Cntnap2-null mice correlates with disrupted synaptic connectivity and increased microglial activity in the anterior cingulate cortex

Matt Dawson, Kevin Gordon-Fleet, Lingxin Yan, Vera Tardos, Huanying He, Kwong Mui, Smriti Nawani , Zeinab Asgarian , Marco Catani, Cathy Fernandes, Uwe Drescher

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

A biological understanding of the apparent sex bias in autism is lacking. Here we have identified Cntnap2 KO mice as a model system to help better understand this dimorphism. Using this model, we observed social deficits in juvenile male KO mice only. These male-specific social deficits correlated with reduced spine densities of Layer 2/3 and Layer 5 pyramidal neurons in the Anterior Cingulate Cortex, a forebrain region prominently associated with the control of social behaviour. Furthermore, in male KO mice, microglia showed an increased activated morphology and phagocytosis of synaptic structures compared to WT mice, whereas no differences were seen in female KO and WT mice. Our data suggest that sexually dimorphic microglial activity may be involved in the aetiology of ASD, disrupting the development of neural circuits that control social behaviour by overpruning synapses at a developmentally critical period.
Original languageEnglish
Article number846
JournalCommunications Biology
Volume6
Issue number1
DOIs
Publication statusPublished - 15 Aug 2023

Keywords

  • MICROGLIA
  • sexual and gender disorders
  • AUTISM

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