Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior
Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior
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DOI：
10.1038/nn.3641
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发表时间：
2014-03-01
影响因子：
25
通讯作者：
Gross, Cornelius T.
中科院分区：
文献类型：
--
作者：
Zhan, Yang;Paolicelli, Rosa C.;Gross, Cornelius T.
小胶质细胞是在大脑发育过程中浸润的吞噬细胞，在大脑成熟过程中突触的消除中起作用。小胶质细胞形态和基因表达的改变与神经发育障碍有关。然而，尚不清楚这些变化是神经元缺陷的主要原因还是次要后果。在这里，我们测试了小胶质细胞的初级缺陷是否足以诱发一些与自闭症相关的行为和功能连接缺陷。缺乏趋化因子受体Cx3cr1的小鼠在出生后早期表现出小胶质细胞的短暂减少和随之而来的突触修剪缺陷。我们发现突触修剪缺陷与突触传递弱、脑功能连通性下降、社会互动缺陷和重复行为表型增加有关，而这些都与自闭症和其他神经发育和神经精神疾病有关。这些发现开启了小胶质细胞介导的突触修剪中断可能导致神经发育和神经精神疾病的可能性。
Microglia are phagocytic cells that infiltrate the brain during development and have a role in the elimination of synapses during brain maturation. Changes in microglial morphology and gene expression have been associated with neurodevelopmental disorders. However, it remains unknown whether these changes are a primary cause or a secondary consequence of neuronal deficits. Here we tested whether a primary deficit in microglia was sufficient to induce some autism-related behavioral and functional connectivity deficits. Mice lacking the chemokine receptor Cx3cr1 exhibit a transient reduction of microglia during the early postnatal period and a consequent deficit in synaptic pruning. We show that deficient synaptic pruning is associated with weak synaptic transmission, decreased functional brain connectivity, deficits in social interaction and increased repetitive-behavior phenotypes that have been previously associated with autism and other neurodevelopmental and neuropsychiatric disorders. These findings open the possibility that disruptions in microglia-mediated synaptic pruning could contribute to neurodevelopmental and neuropsychiatric disorders.