Brain-region specific responses of astrocytes to an in vitro injury and neurotrophins
Brain-region specific responses of astrocytes to an in vitro injury and neurotrophins
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DOI：
10.1016/j.mcn.2018.02.007
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发表时间：
2018-04-01
影响因子：
3.5
通讯作者：
Hugo Masco, Daniel
中科院分区：
文献类型：
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作者：
Beatriz Cragnolini, Andrea;Montenegro, Gonzalo;Hugo Masco, Daniel
星形胶质细胞是胶质细胞的异质群体，其通过称为星形胶质细胞增生的过程对脑损伤作出反应。反应性星形胶质细胞的特征在于增殖、大小、向损伤区的迁移和过多的化学介质如NGF和BDNF的释放的增加。本研究的目的是确定是否有脑区相关的星形胶质细胞的反应，损伤和神经营养因子NGF和BDNF。我们使用划痕损伤模型来研究对从皮层、海马或纹状体获得的单层星形胶质细胞造成的伤口的闭合。我们的研究结果表明，星形胶质细胞的机械损伤的反应不同，根据大脑区域。来自纹状体的星形胶质细胞比来自皮质或海马的星形胶质细胞更快地增殖和重新填充损伤部位。我们发现，划痕损伤诱导神经营养因子受体p75NTR和TrkB.t在星形胶质细胞从所有研究的大脑区域上调。当用NGF处理来自所有区域的星形胶质细胞时，神经营养因子诱导星形胶质细胞的迁移（在Boyden室中评估）并诱导伤口闭合，但不影响增殖。相反，BDNF诱导伤口闭合，但仅在纹状体星形胶质细胞。我们的总体研究结果显示了星形胶质细胞功能的异质性，其基础是它们的大脑起源区域，以及这种功能多样性如何决定它们对损伤和神经营养因子的反应。
Astrocytes are a heterogeneous population of glial cells that react to brain insults through a process referred to as astrogliosis. Reactive astrocytes are characterized by an increase in proliferation, size, migration to the injured zone and release of a plethora of chemical mediators such as NGF and BDNF. The aim of this study was to determine whether there are brain region-associated responses of astrocytes to an injury and to the neurotrophins NGF and BDNF. We used the scratch injury model to study the closure of a wound inflicted on a monolayer of astrocytes obtained from cortex, hippocampus or striatum. Our results indicate that the response of astrocytes to a mechanical lesion differ according to brain regions. Astrocytes from the striatum proliferate and repopulate the injury site more rapidly than astrocytes from cortex or hippocampus. We found that the scratch injury induced the upregulation of neurotrophin receptor p75NTR and TrkB.t in astrocytes from all brain regions studied. When astrocytes from all regions were treated with NGF, the neurotrophin induced migration of the astrocytes (assessed in Boyden chambers) and induced wound closure but did not affect proliferation. In contrast, BDNF induced wound closure but only in astrocytes from striatum. Our overall findings show the heterogeneity in astrocyte functions based on their brain region of origin, and how this functional diversity may determine their responses to an injury and to neurotrophins.