Dataset Information

Sex-Specific Microglia Defects in the Neuroligin-4 Knock-Out Mouse Model of Autism Spectrum Disorder

ABSTRACT: Neuroligin-4 (NL4) loss-of-function mutations are strongly associated with monogenic heritable abnormalities linked with Autism Spectrum Disorder (ASD). NL4 mutation in mice causes ASD related alterations in both, the synaptic and behavioral phenotype. Since microglia closely regulate synaptic development and are implicated as key players in ASD development and progression, we here studied microglial properties in the NL4-/- mouse model. We show that loss of NL4 caused altered behavior and impaired hippocampal gamma oscillations predominantly in male mice. In parallel, microglial density, morphology, and response to injury specifically in the CA3 region of the hippocampus were altered in NL4-deficient males only. A transcriptomic and proteomic analysis revealed a strong impact of sexual dimorphism on molecular alterations in microglia of NL4-deficient compared to wildtype mice. Estrogen application in male NL4-/- animals partially restored the impaired social behavior and the altered microglial phenotype. Together, these results indicate that loss of NL4 affects not only neuronal network activity and behavior, but changes in addition the phenotype of microglia in a sex-specific manner that could be targeted by estrogen treatment.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Microglial Cell

DISEASE(S): Autism Spectrum Disorder

SUBMITTER: Oliver Popp

LAB HEAD: Susanne A. Wolf

PROVIDER: PXD024325 | Pride | 2023-10-24

REPOSITORIES: pride

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Dataset's files

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			Action	DRS
	ANAKIN_20190529_OP_HS_Fem_Hp_KO_b1.raw	Raw
	ANAKIN_20190529_OP_HS_Fem_Hp_KO_b2.raw	Raw
	ANAKIN_20190529_OP_HS_Fem_Hp_KO_b3.raw	Raw
	ANAKIN_20190529_OP_HS_Fem_Hp_WT_e1.raw	Raw
	ANAKIN_20190529_OP_HS_Fem_Hp_WT_e2.raw	Raw

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Publications

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

Guneykaya Dilansu D Ugursu Bilge B Logiacco Francesca F Popp Oliver O Feiks Maria Almut MA Meyer Niklas N Wendt Stefan S Semtner Marcus M Cherif Fatma F Gauthier Christian C Madore Charlotte C Yin Zhuoran Z Çınar Özcan Ö Arslan Taner T Gerevich Zoltan Z Mertins Philipp P Butovsky Oleg O Kettenmann Helmut H Wolf Susanne A SA

Brain, behavior, and immunity 20230329

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 respons ...[more]

PMID: 37001827

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