Neuronal brain-derived neurotrophic factor manipulates microglial dynamics
Neuronal brain-derived neurotrophic factor manipulates microglial dynamics
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DOI：
10.1002/glia.23934
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发表时间：
2020-10-29
期刊：
影响因子：
6.2
通讯作者：
Koyama, Ryuta
中科院分区：
文献类型：
--
作者：
Onodera, Junya;Nagata, Hidetaka;Koyama, Ryuta
脑源性神经营养因子(BDNF)是神经营养因子家族中的主要成员，活跃在大脑中，支持神经元的生存和生长。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，我们研究了BDNF对海马区CA3区小胶质细胞特性的影响。我们选择这个地点是因为海马苔藓纤维的轴突主要形成于CA3区，含有啮齿类动物大脑中最高水平的BDNF。我们用一种同时编码BDNF短发夹状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，以检测苔藓纤维来源的BDNF对小胶质细胞的影响。免疫组织化学显示，用shRNA敲除BDNF后，苔藓纤维通路中的小胶质细胞密度增加，苔藓纤维轴突被小胶质细胞吞噬的程度增加。此外，我们对海马片培养的小胶质细胞突起进行了时间推移成像，以检测BDNF对小胶质细胞运动的影响。时间推移成像显示，当BDNF信号被药物阻断时，小胶质细胞突起的运动性增加，并吞噬苔藓纤维突触。因此，神经元BDNF可以防止小胶质细胞吞噬海马区苔藓纤维突触。
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.