突触修剪
免疫学
突触可塑性
长时程增强
树突棘
小胶质细胞
医学
生物
化学
神经科学
炎症
内科学
海马结构
受体
作者
Fangfang Qi,Zejie Zuo,Sifan Hu,Yucen Xia,Dan Song,Jiechen Kong,Yang Yang,Yingying Wu,Xiao Wang,Junhua Yang,Dandan Hu,Qing Yuan,Juntao Zou,Guo Ke,Jie Xu,Zhibin Ye
标识
DOI:10.1016/j.bbi.2018.04.003
摘要
Activation of the neonatal immune system may contribute to deficits in neuronal plasticity. We have reported that neonatal vaccination with a hepatitis B vaccine (HBV) transiently impairs mood status and spatial memory involving a systemic T helper (Th) 2 bias and M1 microglial activation. Here, an EE induced microglial anti-inflammatory M2 polarization, as evidenced by selectively enhanced expression of the Arginase1 gene (Arg-1) in the hippocampus. Interestingly, knock-down of the Arg-1 gene prevented the effects of EE on restoring the dendritic spine density. Moreover, levels of the Th1-derived cytokine IFN-gamma (IFN-γ) were elevated in the choroid plexus (CP), which is the interface between the brain and the periphery. IFN-γ-blocking antibodies blunted the protective effects of an EE on spine density and LTP. Furthermore, levels of complement proteins C1q and C3 were elevated, and this elevation was associated with synapse loss induced by the HBV, whereas an EE reversed the effects of the HBV. Similarly, blockade of C1q activation clearly prevented synaptic pruning by microglia, LTP inhibition and memory deficits in hepatitis B-vaccinated mice. Together, the EE-induced increase in IFN-γ levels in the CP may disrupt systemic immunosuppression related to HBV via an IFN-γ/Arg-1/complement-dependent pathway.
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