Heterogeneity of microglial proton channel in different brain regions and its relationship with aging.
Heterogeneity of microglial proton channel in different brain regions and its relationship with aging.
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不同脑区小胶质细胞质子通道的异质性及其与衰老的关系。
DOI：
10.1111/jnc.15292
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Kawai T,Takao K,Akter S,Abe M,Sakimura K,Miyakawa T,Okamura Y
中科院分区：
文献类型：
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作者：
Takuto Fujii;Mizuki Katoh;Takahiro Shimizu;Shushi Nagamori;Keiichi Koizumi, Junya Fukuoka;Yoshiaki Tabuchi;Akira Sawaguchi;Tomoyuki Okumura;Kazuto Shibuya;Tsutomu Fujii;Hiroshi Takeshima;Hideki Sakai;Kawai T,Takao K,Akter S,Abe M,Sakimura K,Miyakawa T,Okamura Y
小胶质细胞的特性在很大程度上取决于年龄以及大脑区域。然而，很少有研究在分子水平上研究小胶质细胞这种异质性的功能重要性。电压门控质子通道Hv 1/VSOP可能是赋予小胶质细胞功能异质性的候选者之一，因为它以年龄依赖性方式调节脑氧化应激。在这项研究中，我们发现Hv 1/VSOP显示出大脑区域依赖性的基因表达异质性，在纹状体中水平最高。我们研究了Hv 1/VSOP在两个不同大脑区域（大脑皮层和纹状体）中的重要性，并研究了它们与衰老的关系（使用不同年龄的小鼠）。在皮质中，我们观察到Hv 1/VSOP对氧化应激、小胶质细胞形态和基因表达谱的年龄依赖性影响。另一方面，我们发现Hv 1/VSOP的年龄依赖性意义在纹状体中不如皮质明显。最后，我们对年轻和老年阶段的Hv 1/VSOP缺陷小鼠进行了一系列行为实验，以检查衰老对Hv 1/VSOP功能的影响。Hv 1/VSOP缺陷型小鼠仅在老龄阶段的明/暗转换试验中表现出明显的行为差异，表明老年Hv 1/VSOP小鼠的焦虑状态发生了改变。这项研究表明，脑区异质性和动物衰老的结合强调了Hv 1/VSOP在小胶质细胞中的功能重要性。
The properties of microglia largely differ depending on aging as well as on brain regions. However, there are few studies that investigated the functional importance of such heterogeneous properties of microglia at the molecular level. Voltage‐gated proton channel, Hv1/VSOP, could be one of the candidates which confers functional heterogeneity among microglia since it regulates brain oxidative stress in age‐dependent manner. In this study, we found that Hv1/VSOP shows brain region‐dependent heterogeneity of gene expression with the highest level in the striatum. We studied the importance of Hv1/VSOP in two different brain regions, the cerebral cortex and striatum, and examined their relationship with aging (using mice of different ages). In the cortex, we observed the age‐dependent impact of Hv1/VSOP on oxidative stress, microglial morphology, and gene expression profile. On the other hand, we found that the age‐dependent significance of Hv1/VSOP was less obvious in the striatum than the cortex. Finally, we performed a battery of behavioral experiments on Hv1/VSOP‐deficient mice both at young and aged stages to examine the effect of aging on Hv1/VSOP function. Hv1/VSOP‐deficient mice specifically showed a marked difference in behavior in light/dark transition test only at aged stages, indicating that anxiety state is altered in aged Hv1/VSOP mice. This study suggests that a combination of brain region heterogeneity and animal aging underscores the functional importance of Hv1/VSOP in microglia.