六羟多巴胺对成年小鼠黑质-纹状体系统多巴胺能神经元及其行为学的影响

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。

Effects of 6-hydroxydopamine on dopaminergic neurons in nigrostriatal system and on behavior of adult mice

Objective To evaluate the proliferation of endogenous neural progenitor cells (NPCs) and its effect on the recovery of injured nigrostiatal system following mesencephalic substantia nigra lesion.Methods The proliferation of NPCs derived from the surrounding regions of the lateral ventricle,the third ventricle (3V) and the cerebral aqueduct (Aq) as well as the midbrain were investigated using immunofluorescent staining on days 3-35 following 6-hydroxydopamine (6-OHDA) injection into the unilateral substantia nigra (SN) of the adult mice.In addition,the proliferation of the SN newborn cells and their differentiation into mature neurons or dopaminergic neurons were explored.Finally,behavioral changes of mice were examined by open field and rotarod tests (n =4-6,each group).Results The 6-OHDA-induced loss of dopaminergic neurons in the SN significantly increased the numbers of NPCs from the subventricular zone in the surrounding regions of 3V and Aq,which was most obvious on day 7 following 6-OHDA injection.The number of SN newborn cells and new-generated dopaminergic neurons reached to the peak on day 21 following 6-OHDA injection,which possibly resulted in a partial restoration in the lesioned nigrastriatum system and behavioral performance of mice.Conclusion It might be an ideal strategy to deal with Parkinson's disease by promoting the proliferation and differentiation of endogenous NPCs.