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Sex-specific microglia state in the neuroligin-4 knock-out mouse model of autism spectrum disorder

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Item Type:Article
Title:Sex-specific microglia state in the neuroligin-4 knock-out mouse model of autism spectrum disorder
Creators Name:Guneykaya, D. and Ugursu, B. and Logiacco, F. and Popp, O. and Feiks, M.A. and Meyer, N. and Wendt, S. and Semtner, M. and Cherif, F. and Gauthier, C. and Madore, C. and Yin, Z. and Çınar, Ö. and Arslan, T. and Gerevich, Z. and Mertins, P. and Butovsky, O. and Kettenmann, H. and Wolf, S.A.
Abstract:Neuroligin-4 (NLGN4) loss-of-function mutations are associated with monogenic heritable autism spectrum disorder (ASD) and cause alterations in both synaptic and behavioral phenotypes. Microglia, the resident CNS macrophages, are implicated in ASD development and progression. Here we studied the impact of NLGN4 loss in a mouse model, focusing on microglia phenotype and function in both male and female mice. NLGN4 depletion caused lower microglia density, less ramified morphology, reduced response to injury and purinergic signaling specifically in the hippocampal CA3 region predominantly in male mice. Proteomic analysis revealed disrupted energy metabolism in male microglia and provided further evidence for sexual dimorphism in the ASD associated microglial phenotype. In addition, we observed impaired gamma oscillations in a sex-dependent manner. Lastly, estradiol application in male NLGN4(-/-) mice restored the altered microglial phenotype and function. Together, these results indicate that loss of NLGN4 affects not only neuronal network activity, but also changes the microglia state in a sex-dependent manner that could be targeted by estradiol treatment.
Keywords:Microglia, Purinergic Signaling, Autism Spectrum Disorder, Gamma Oscillation, Sex Difference, Animals, Mice
Source:Brain Behavior and Immunity
Page Range:61-75
Date:July 2023
Official Publication:https://doi.org/10.1016/j.bbi.2023.03.023
PubMed:View item in PubMed

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