小胶质细胞
自闭症
翻译(生物学)
突触
神经科学
蛋白质生物合成
生物
平衡
细胞生物学
医学
免疫学
信使核糖核酸
遗传学
精神科
炎症
基因
作者
Zhi Xu,Gyu Hyun Kim,Ji Wei Tan,Anna Riso,Ye Sun,Ethan Y. Xu,Guey Ying Liao,Haowen Xu,Sang Hoon Lee,Young Na,Chan Hee Lee,Amy E. Clipperton-Allen,Sung-Kyu Kwon,Damon T. Page,Kea Joo Lee
标识
DOI:10.1038/s41467-020-15530-3
摘要
Abstract Mutations that inactivate negative translation regulators cause autism spectrum disorders (ASD), which predominantly affect males and exhibit social interaction and communication deficits and repetitive behaviors. However, the cells that cause ASD through elevated protein synthesis resulting from these mutations remain unknown. Here we employ conditional overexpression of translation initiation factor eIF4E to increase protein synthesis in specific brain cells. We show that exaggerated translation in microglia, but not neurons or astrocytes, leads to autism-like behaviors in male mice. Although microglial eIF4E overexpression elevates translation in both sexes, it only increases microglial density and size in males, accompanied by microglial shift from homeostatic to a functional state with enhanced phagocytic capacity but reduced motility and synapse engulfment. Consequently, cortical neurons in the mice have higher synapse density, neuroligins, and excitation-to-inhibition ratio compared to control mice. We propose that functional perturbation of male microglia is an important cause for sex-biased ASD.
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