不同亚型中脑多巴胺能神经元在帕金森病治疗中的功能差异

Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system，which is mainly manifested as movement disorders. The pathological basis of PD is due to the degeneration of dopaminergic neurons of the substantia nigra, and there are no clinically effective means to cure PD. One of the promising methods is to replace dopaminergic neurons in the brain by the transplantation of dopaminergic neurons. A9 and A10 neurons are two important subtypes of midbrain dopaminergic neurons. A9 neurons distribute in the substantia nigra and regulate motor functions, while A10 neurons distribute in the ventral tegmental area and are involved in the regulation of reward and emotion functions. The functional differences of the endogenous A9/A10 DA neurons suggest that they may have different roles in the treatment of PD. We have obtained different subtypes of DA neurons by optimizing the neural differentiation system of the multipotent stem cells. On this basis, we will further study the similarities and differences between different subtypes of DA neurons in the treatment of motor dysfunction of PD model. This study will provide an important theoretical basis for the selection of therapeutic strategies for PD.

帕金森病（PD）是一种以运动功能障碍为主要表型的中枢神经系统退行性疾病，主要病理特征是中脑黒质多巴胺能（DA）神经元的退行性变。临床上尚无治愈PD的有效手段，外源移植中脑DA神经元（干细胞治疗），是具有前景的治疗方法之一。内源中脑DA神经元含有两种重要亚型，包括位于黑质的A9 DA神经元和位于腹侧被盖区的A10 DA神经元，其支配的脑区和生理功能完全不同。A9神经元主要调控运动功能；而A10神经元主要参与调控奖赏、情绪等。现在PD细胞治疗的研究中，并没有区分这两种不同亚型的DA神经元，然而内源A9/A10 DA神经元亚型的功能差异提示其在PD细胞治疗中的作用的不同。申请人通过优化人多能干细胞神经定向分化系统得到了不同亚型DA神经元富集的分化产物。在这一基础上，拟进一步研究不同亚型DA神经元治疗PD模型动物运动功能障碍的异同及其机制。这一研究将为PD细胞治疗策略的选择提供重要的理论依据。