6-OHDA诱导大鼠多巴胺神经元选择性缺失的研究

目的 电压依赖性钙离子通道分布对6-羟基多巴胺（6-OHDA）诱导的SD大鼠多巴胺能神经元缺失的影响.方法 6-OHDA单侧脑内内侧前脑束（MFB）立体定位注射,术后10d观测行为学变化;并取脑固定,免疫组化酪氨酸羟化酶（TH）染色观察中脑黑质致密部（SNc）与腹侧背盖区（VTA）多巴胺能神经元的凋亡情况.并应用膜片钳全细胞记录技术,测量SNc与VTA多巴胺能神经元的电压依赖性钙离子通道的电流密度.结果 损伤侧的SNc区TH阳性细胞与对侧比较明显减少,而VTA区TH阳性细胞与对侧相比变化较小;全细胞记录电压膜片钳技术测量,发现SNc多巴胺能神经元钙通道电流密度与VTA相比明显较高.结论 该结果的发现,提示钙离子通道可能参与到帕金森氏病中脑多巴胺能神经元的选择性凋亡的机制.

Neurotoxin 6-OHDA induced vulnerability of dopamine neurons in rat substantia nigra compacta and ventral

To investigate the relationship between the distribution of voltage gated calcium channel （VGCC） and the vulnerability of dopaminergic （DA） neurons in substantia nigra compacta （SNc） and ventral tegmental area （VIA）. Methods After 6-hydroxydopamine （6-OHDA） injection, the behavior features of rats were investigated in the following 10 d. TH staining showed the apoptosis level of DA neurons in the beth SNc and VTA. Whole cell patching clamp technique was applied for measuring the amplitude of voltage gated calcium current density. Rt~mlts It was showed that TH positive neurons in SNc obviously were decreased in lesion side, while in VIA the TH positive neurons were less changed in numbers. The amplitude of voltage gated calcium current in SNc DA neurons was significantly larger than that of VIA. Conclusion The expression of VGCC differs in SNc and VTA following the death of dopaminergic neurons, indicating that the VGCC nmy be involved in the mechanism of 6-OHDA induced vulnerability in PD model.