帕金森病多巴胺能神经元模型的建立(英文)

Dopaminergic neuron as the cell model for Parkinson's disease

帕金森病是一种常见的中枢神经系统进行性退行性病变,其病因机制尚未明确,且缺乏令人满意的治疗方法。因此,建立有效的帕金森病模型对其病因机制的进一步探讨有着重要的意义。Berger等人于1982年建立腹侧中脑原代细胞培养方法,通常应用小鼠或大鼠胚胎(13～15 d胎龄)中脑组织进行培养。多巴胺能神经元可在体外存活长达数月,因此,可为多巴胺能神经元急性或慢性损伤的病因机制的研究提供实验手段。多巴胺能神经元在体外可通过免疫化学、放射自显影及荧光组织化学等方法确认。故其形态学及数量上的改变在体外较容易被检测,因而这种实验模型的建立对于帕金森病病因机制及新的治疗方法的探讨将起着重要的作用。

Parkinson's disease (PD) is a progressive degenerative disorder of the central nervous system. The etiology and molecular mechanism of PD remain unclear. Though effective treatment exists for most cases at its onset, the symptoms become resistant as time goes on and the underlying neurodegeneration cannot be stopped. Therefore, it is very necessary to establish animal and cell culture models reflecting the pathological changes and the efficacy of treatment. Next to neurotoxic studies with MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) in monkeys and mice, cell cultures of dissociated fetal nigral tissue including dopaminergic cells of the mesencephalon are currently used. The technique of preparing primary culture of ventral mesencephalon was put forward by Berger and his colleagues in 1982. Dissociated ventral mesencephalic tissue from mice or rat embryos at gestation day 13 to 15 usually was used to make primary cell culture in which the dopaminergic neurons can be maintained for several months. So such a long term culture system can be developed in vitro permits studies on both acute and chronic lesions in dopaminergic neurons. Radioligands, fluorescence microscopy and immunohistochemistry for tyrosine hydroxylase have been used to identify dopaminergic neurons. Changes in morphology and loss of the dopaminergic neurons can be easily detected, so this cell model will play an important role in the research of etiology, mechanism and novel treatments of PD.