Glial Phagocytic Receptors Promote Neuronal Loss in Adult Drosophila Brain
Glial Phagocytic Receptors Promote Neuronal Loss in Adult Drosophila Brain
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DOI：
10.1016/j.celrep.2019.09.086
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发表时间：
2019-11-05
期刊：
影响因子：
8.8
通讯作者：
Kurant, Estee
中科院分区：
文献类型：
--
作者：
Hakim-Mishnaevski, Ketty;Flint-Brodsly, Naama;Kurant, Estee
神经胶质细胞的吞噬作用对于脊椎动物和苍蝇中CNS的发育和维持至关重要，并且依赖于吞噬受体的功能来清除凋亡细胞和碎片。胶质细胞吞噬能力随着年龄的增长而下降，这与神经元功能障碍相关，表明胶质细胞吞噬作用的增加可以防止神经变性。与这一假设相矛盾的是，我们提供的实验证据表明，成年果蝇胶质细胞中吞噬受体Six-Microns-Under（SIMU）和德雷珀（Drpr）的表达升高会导致多巴胺能和GABA能神经元的丧失，并伴有运动功能障碍和寿命缩短。重要的是，这种神经元数量的减少与神经元凋亡无关，而是与磷脂酰丝氨酸介导的超吞噬胶质细胞对活神经元的吞噬作用有关。总而言之，我们的研究表明，神经胶质吞噬细胞受体的水平必须严格调节适当的脑功能，神经变性不仅发生缺陷，而且过度的胶质细胞功能。
Glial phagocytosis is critical for the development and maintenance of the CNS in vertebrates and flies and relies on the function of phagocytic receptors to remove apoptotic cells and debris. Glial phagocytic ability declines with age, which correlates with neuronal dysfunction, suggesting that increased glial phagocytosis may prevent neurodegeneration. Contradicting this hypothesis, we provide experimental evidence showing that an elevated expression of the phagocytic receptors Six-Microns-Under (SIMU) and Draper (Drpr) in adult Drosophila glia leads to a loss of both dopaminergic and GABAergic neurons, accompanied by motor dysfunction and a shortened lifespan. Importantly, this reduction in neuronal number is not linked to neuronal apoptosis, but rather to phosphatidylserine-mediated phagoptosis of live neurons by hyper-phagocytic glia. Altogether, our study reveals that the level of glial phagocytic receptors must be tightly regulated for proper brain function and that neurodegeneration occurs not only by defective, but also excessive glial cell function.