Differential activation of astrocytes and microglia during post-natal development of dopaminergic neuronal death in the weaver mouse
Differential activation of astrocytes and microglia during post-natal development of dopaminergic neuronal death in the weaver mouse
复制标题
DOI：
10.1016/s0165-3806(03)00190-1
复制
发表时间：
2003-10-10
期刊：
影响因子：
--
通讯作者：
Raisman-Vozari, R
中科院分区：
文献类型：
--
作者：
Douhou, A;Debeir, T;Raisman-Vozari, R
为了了解星形胶质细胞、小胶质细胞和受损神经元之间的关系，我们研究了织布突变小鼠。该突变体的主要特征之一是多巴胺能 (DA) 黑质纹状体通路的进行性变性，该通路在出生后第 15 天 (P15) 左右开始，在黑质致密部 (SNpc) 中，并进展直至成年 (P60)。在本文中，我们分析了纯合织布小鼠黑质纹状体系统中 DA 神经元内星形胶质细胞和小胶质细胞之间的关系，这些细胞在不同的出生后年龄对应于 DA 神经元丢失的特定阶段。星形胶质细胞的激活被发现是 weaver DA 去神经支配的早期事件，在 P15 的 SNpc 中 DA 神经元丢失开始时大量出现。即使在神经元死亡过程减慢之后，星形胶质细胞在成人大脑中仍然保持激活状态。有趣的是，在未检测到 DA 神经元死亡的腹侧被盖区，在成年动物中也观察到了严重的、永久性的星形胶质细胞增生。相比之下，在 SNpc 中短暂观察到小胶质细胞的激活，但仅在出生后观察到最大神经元死亡时 (P30)。最后，在纹状体中，DA 神经末梢大量丢失，没有检测到星形胶质细胞增生和小胶质细胞激活。因此，星形胶质细胞和小胶质细胞对进行性和自发性 DA 神经元死亡的反应表现出不同的时间动力学，表明这两种细胞类型在织布小鼠的 DA 神经退行性过程中发挥着不同的作用。 (C) 2003 Elsevier B.V. 保留所有权利。
In order to understand the relationship between astrocytes, microglia and injured neurons, we studied the weaver mutant mouse. One of the main characteristics of this mutant is the progressive degeneration of the dopaminergic (DA) nigrostriatal pathway that starts around postnatal day 15 (P15), in the substantia nigra pars compacta (SNpc) and progresses until adult age (P60). In the present paper, we analysed the relationship between astroglial and microglial cells within DA neurons in the nigrostriatal system of homozygous weaver mice, at different postnatal ages corresponding to specific stages of the DA neuronal loss. The activation of astrocytes was found to be an early event in weaver DA denervation, appearing massively at the onset of DA neuronal loss in the SNpc at P15. Astrocytes remained activated in the adult brain even after the slowing down of the neuronal death process. Interestingly, in the ventral tegmental area, where no DA neuronal death could be detected, a profound, permanent astrogliosis was also observed in adult animals. In contrast, an activation of microglial cells was transiently observed in the SNpc but only at the postnatal age when maximal neuronal death was observed (P30). Lastly, in the striatum, where there was a massive loss of DA nerve terminals, neither astrogliosis nor microglial activation was detected. Hence, the reaction of astrocytes and microglial cells to progressive and spontaneous DA neuronal death showed different temporal kinetics, suggesting a different role for these two cell types in the DA neurodegenerative process in the weaver mouse. (C) 2003 Elsevier B.V. All rights reserved.