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目的评估中脑黑质损伤后内源性神经前体细胞(NPCs)的增殖情况及其对黑质-纹状体系统损伤后恢复的促进作用。方法向成年小鼠的一侧黑质(SN)注射六羟多巴胺(6-OHDA),损伤后3~35 d运用免疫荧光染色等方法,研究小鼠来自侧脑室、第三脑室、中脑水管周围及中脑部分NPCs的增殖,探索黑质中新生细胞的增殖及其向成熟神经元、多巴胺能神经元分化的情况,最后通过旷场和转棒实验检测小鼠行为学的变化(每组n=4~6)。结果黑质内注射6-OHDA引起的多巴胺能神经元损失可以明显增加第三脑室和中脑水管周围来自室管膜下区的NPCs的数目,以6-OHDA注射后的第7天最为明显,且6-OHDA注射后第21天黑质内新生细胞和新生多巴胺能神经元的数目增加达到高峰,这些变化可能导致了受损的黑质-纹状体系统及小鼠行为学表现有部分恢复。结论促进内源性NPCs的增殖和分化将成为治疗帕金森病的理想手段。
Objective To evaluate the proliferation of endogenous neural precursor cells (NPCs) after mesencephalic injury in midbrain and their effects on the recovery of substantia nigra and striatal system injury. Methods 6-OHDA (6-OHDA) was injected into the substantia nigra (SN) of adult mice. Immunofluorescence staining was performed 3 to 35 days after injury to study the effects of intracerebroventricular injection Peripheral and midbrain NPCs proliferation, to explore the proliferation of substantia nigra neovascularization and its differentiation into mature neurons, dopaminergic neurons, and finally open-field and rotating rod test mice behavioral changes (each group n = 4 ~ 6). Results The loss of dopaminergic neurons caused by intra-substantia nigra injection of 6-OHDA significantly increased the number of NPCs from the subependymal zone around the third ventricle and midbrain ducts, most notably on day 7 after 6-OHDA injection, Moreover, the number of neonate cells and neoplasm dopaminergic neurons peaked on the 21st day after injection of 6-OHDA, and these changes may lead to partial recovery of the damaged nigrostriatal system and mouse behavioral manifestations . Conclusions Promote the proliferation and differentiation of endogenous NPCs will be an ideal means to treat Parkinson’s disease.