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Neuronal brain‐derived neurotrophic factor manipulates microglial dynamics
Glia ( IF 5.4 ) Pub Date : 2020-10-29 , DOI: 10.1002/glia.23934
Junya Onodera 1 , Hidetaka Nagata 2 , Ai Nakashima 1 , Yuji Ikegaya 1 , Ryuta Koyama 1
Affiliation  

Brain‐derived neurotrophic factor (BDNF), a main member of the neurotrophin family that is active in the brain, supports neuronal survival and growth. Microglial BDNF affects both the structural and functional properties of neurons. In contrast, whether and how neuronal BDNF affects microglial dynamics remain largely undetermined. Here, we examined the effects of BDNF on the properties of microglia in the CA3 region of the hippocampus. We chose this site because the axonal boutons of hippocampal mossy fibers, which are mostly formed in the CA3 region, contain the highest levels of BDNF in the rodent brain. We transfected mouse dentate granule cells with an adeno‐associated virus that encodes both a BDNF short hairpin RNA (shRNA) and red fluorescent protein to examine the effects of mossy fiber‐derived BDNF on microglia. Based on immunohistochemistry, BDNF knockdown with an shRNA resulted in an increase in microglial density in the mossy fiber pathway and increased engulfment of mossy fiber axons by microglia. In addition, we performed time‐lapse imaging of microglial processes in hippocampal slice cultures to examine the effects of BDNF on microglial motility. Time‐lapse imaging revealed increases in the motility of microglial processes and the engulfment of mossy fiber synapses by microglia when BDNF signaling was pharmacologically blocked. Thus, neuronal BDNF prevents microglia from engulfing mossy fiber synapses in the hippocampus.

中文翻译:

神经元脑源性神经营养因子操纵小胶质细胞动力学

脑源性神经营养因子 (BDNF) 是在大脑中活跃的神经营养因子家族的主要成员,支持神经元的存活和生长。小胶质细胞 BDNF 影响神经元的结构和功能特性。相比之下,神经元 BDNF 是否以及如何影响小胶质细胞动力学在很大程度上仍未确定。在这里,我们检查了 BDNF 对海马 CA3 区域小胶质细胞特性的影响。我们选择这个站点是因为海马苔藓纤维的轴突环,主要在 CA3 区域形成,在啮齿动物大脑中含有最高水平的 BDNF。我们用编码 BDNF 短发夹 RNA (shRNA) 和红色荧光蛋白的腺相关病毒转染小鼠齿状颗粒细胞,以检查苔藓纤维衍生的 BDNF 对小胶质细胞的影响。基于免疫组织化学,用 shRNA 敲低 BDNF 导致苔藓纤维通路中的小胶质细胞密度增加,并增加了小胶质细胞对苔藓纤维轴突的吞噬。此外,我们对海马切片培养物中的小胶质细胞过程进行了延时成像,以检查 BDNF 对小胶质细胞运动的影响。延时成像显示,当 BDNF 信号被药理学阻断时,小胶质细胞过程的运动性增加和小胶质细胞吞噬苔藓纤维突触。因此,神经元 BDNF 防止小胶质细胞吞噬海马中的苔藓纤维突触。我们对海马切片培养物中的小胶质细胞过程进行了延时成像,以检查 BDNF 对小胶质细胞运动的影响。延时成像显示,当 BDNF 信号被药理学阻断时,小胶质细胞过程的运动性增加和小胶质细胞吞噬苔藓纤维突触。因此,神经元 BDNF 防止小胶质细胞吞噬海马中的苔藓纤维突触。我们对海马切片培养物中的小胶质细胞过程进行了延时成像,以检查 BDNF 对小胶质细胞运动的影响。延时成像显示,当 BDNF 信号被药理学阻断时,小胶质细胞过程的运动性增加和小胶质细胞吞噬苔藓纤维突触。因此,神经元 BDNF 防止小胶质细胞吞噬海马中的苔藓纤维突触。
更新日期:2020-10-29
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