Profound astrogenesis in the striatum of adult mice following nigrostriatal dopaminergic lesion by repeated MPTP administration
Profound astrogenesis in the striatum of adult mice following nigrostriatal dopaminergic lesion by repeated MPTP administration
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DOI：
10.1016/s0165-3806(01)00260-7
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发表时间：
2001-11-26
期刊：
影响因子：
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通讯作者：
Wang, JQ
中科院分区：
文献类型：
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作者：
Mao, LM;Lau, YS;Wang, JQ
神经祖细胞在整个成年期都存在于啮齿动物的大脑中，并且可以增殖和分化成新的神经元和/或神经胶质以修复损伤。为了探讨脑祖细胞介导的修复过程，通过重复给予神经毒素1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导年轻成年小鼠黑质纹状体多巴胺能通路的选择性损伤。一种胸苷类似物，溴脱氧尿苷（BrdU），被用作DNA合成的示踪剂，以标记损伤后的分裂细胞及其末端后代。MPTP治疗（25 mg/kg，每日一次，持续5天）后3天，在背侧纹状体中观察到BrdU标记的新生细胞数量增加了8倍。在黑质（SN）中也观察到5倍增加。纹状体中的新生细胞在出生后存活超过60天，而SN中的新生细胞存活不到31天。纹状体中的绝大多数新生细胞在出生后10天内根据其放射状形态和与星形胶质细胞标志物S100 β的共表达分化为星形胶质细胞。相反，SN中的大多数BrdU阳性细胞不能共表达S100 β。很少或没有BrdU标记的细胞在纹状体和SN被发现与神经元标记物，神经元核抗原，或酪氨酸羟化酶共定位在整个过程中的生存天数调查（3至60天）。重复MPTP也降低纹状体多巴胺含量和摄取，MPTP损伤后31天明显恢复。这些结果表明，一个快速和深刻的星形胶质细胞在纹状体的年轻成年小鼠在响应毒性多巴胺能损伤。在两个受影响的脑区缺乏神经发生表明神经胶质细胞再生在修复MPTP损伤中的相对重要性。(C)2001 Elsevier Science B. V.保留所有权利。
Neural progenitor cells are present in the rodent brain throughout adulthood, and can proliferate and differentiate into new neurons and/or glia to repair injury. To explore the repair processes mediated by brain progenitor cells, a selective lesion of the nigrostriatal dopaminergic pathway was induced in young adult mice by repeated administration of the neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). A thymidine analog, bromodeoxyuridine (BrdU), was used as a tracer for DNA synthesis to label the dividing cells and their terminal progeny following injury. Three days after MPTP treatments (25 mg/kg, once daily for 5 days), an 8-fold increase in the number of BrdU-labeled newborn cells was observed in the dorsal striatum. A 5-fold increase was also seen in the substantia nigra (SN). Newborn cells in the striatum survived beyond 60 days after their birth whereas newborn cells in the SN survived for less than 31 days. The vast majority of newborn cells in the striatum differentiated into astroglia according to their radial morphology and co-expression with an astroglial marker, S100 beta, within 10 days after birth. In contrast, most BrdU-positive cells in the SN failed to co-express S100 beta. Little or none of BrdU-labeled cells in both the striatum and SN were found to co-localize with a neuronal marker, neuronal nuclear antigen, or tyrosine hydroxylase during the full course of survival days surveyed (3 to 60 days). Repeated MPTP also decreased dopamine content and uptake in the striatum, which showed a significant recovery 31 days after MPTP lesion. These results demonstrate a rapid and profound astrogenesis in the striatum of young adult mice in response to toxic dopaminergic insult. The lack of neurogenesis in the two affected brain areas indicates the relative importance of glial cell regeneration in repairing MPTP injury. (C) 2001 Elsevier Science B.V. All rights reserved.