Prenatally VPA exposure is likely to cause autistic-like behavior in the rats offspring via TREM2 down-regulation to affect the microglial activation and synapse alterations.
Prenatally VPA exposure is likely to cause autistic-like behavior in the rats offspring via TREM2 down-regulation to affect the microglial activation and synapse alterations.
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DOI：
10.1016/j.etap.2023.104090
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发表时间：
2023-03
影响因子：
4.3
通讯作者：
Lijuan Luo;Jie Chen;Qionghui Wu;Binlin Yuan;Chaoqun Hu;Ting Yang;Hua Wei;Tingyu Li
中科院分区：
文献类型：
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作者：
Lijuan Luo;Jie Chen;Qionghui Wu;Binlin Yuan;Chaoqun Hu;Ting Yang;Hua Wei;Tingyu Li
在丙戊酸（VPA）诱导的自闭症谱系障碍（ASD）大鼠模型中有小胶质细胞功能障碍的报道。然而，产前VPA暴露如何影响小胶质细胞仍有待阐明。髓样细胞2上表达的触发受体（TREM2）被发现与一系列小胶质细胞功能有关。然而，关于TREM2与vpa诱导的ASD大鼠模型之间关系的报道很少。我们的研究结果表明，产前VPA暴露诱导后代的自闭症样行为，下调TREM2水平，上调小胶质细胞激活，失调小胶质细胞极化，改变突触。TREM2过表达部分改善了产前vpa暴露大鼠的小胶质细胞功能障碍和自闭症样行为。我们的研究结果首次表明，产前暴露于VPA可能通过TREM2下调影响小胶质细胞激活、小胶质细胞极化和小胶质细胞突触修剪而导致大鼠后代出现自闭症样行为。
Microglial dysfunction has been reported in the valproic acid (VPA)-induced autism spectrum disorder (ASD) rat models. However, how does prenatal VPA exposure affect microglia remains to be elucidated. The triggering receptor expressed on myeloid cells 2 (TREM2) is revealed to be implicated in a range of microglia functions. However, reports on the association between TREM2 and VPA-induced ASD rat models are scarce. Our results showed that prenatal VPA exposure induced autistic-like behaviors, downregulated the levels of TREM2, up-regulated microglial activation, dysregulated microglial polarization, and altered synapse in offspring. TREM2 overexpression partly ameliorated microglia dysfunction and autistic-like behaviors in prenatal VPA-exposed rats. Our findings demonstrated that prenatally VPA exposure is likely to cause autistic-like behavior in the rat offspring via TREM2 down-regulation to affect the microglial activation, microglial polarization and synaptic pruning of microglia for the first time.