不同帕金森病模型小鼠空间参考记忆及脑内多巴胺水平的比较研究

目的 比较1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)所致的急性、亚急性和慢性帕金森病(PD)模型小鼠空间参考记忆和脑内多巴胺(DA)水平的差异.方法 用相同的MPTP使用总量不同的注射间隔分别制作急性、亚急性和慢性PD小鼠模型.Morris水迷宫检测小鼠空间参考记忆,高效液相(HPLC)检测纹状体、海马和前额叶皮层的DA含量,免疫组化染色检测黑质酪氨酸羟化酶(TH)阳性神经元数量.结果 慢性PD小鼠的逃避潜伏期较对照组有明显延长(P＜0.05),而急性和亚急性PD小鼠则无明显变化.3组实验组纹状体DA含量[(1180.1±293.0)ng/ml,(1177.4±450.5)ng/ml,(1149.6±353.0)ng/ml]均较对照组[(225.6±79.7)ng/ml,(273.6±64.9)ng/ml,(327.1±126.2)ng/ml]有显著减少(P＜0.01),急性PD小鼠前额叶皮层DA含量[(65.3±23.9)ng/ml]较对照组[(41.2±18.8)ng/ml]有显著减少(P＜0.05),3组实验组海马DA含量无明显变化.3组实验组黑质TH阳性神经元数量均较对照组有显著减少(P＜0.05).结论 3种PD模型小鼠空间参考记忆差异可能不是由其脑内DA水平差异所致.

A comparison of spatial reference memory and dopamine level in the brain between different mouse models of Parkinson's disease

Objective To compare the difference of spatial reference memory and dopamine (DA) level in the brain between acute,subacute and chronic mouse model of Parkinson' s disease(PD) induced by 1-methyl-4-phenyl-1 ,2,3,6-tetrahydropyridine(MPTP) injection. Methods The acute,subacute and chronic mouse model of Parkinson' s disease were induced by injecting the same MPTP volume dose with different schedules. The spatial reference memory of mice was tested by morris water maze. Dopamine concentration in striatum, hippocampus and the prefrontal cortex were detected with HPLC. The number of tyrosine hydroxylase(TH)-positive cells in the substantia nigra of mice was detected by immunohistochemistry. Results The mean escape latency of the chronic but not the acute or subacute mouse model of Parkinson' s disease was significant longer ( P ＜ 0.05 ) than its control group. The striatum DA concentration of three test groups ( ( 1180. 1 ± 293.0 ) ng/ml, ( 1177.4 ± 450.5 ) ng/ml,( 1149.6 ± 353.0 ) ng/ml ) reduced significantly compared to their control groups ( ( 225.6 ± 79.7 ) ng/ml, ( 273.6± 64.9 ) ng/ml, ( 327. 1 ± 126.2 ) ng/ml, P ＜ 0.01 ). The prefrontal cortex DA concentration of the acute mouse model of Parkinson' s disease ( ( 65.3 ± 23.9 ) ng/ml ) was significant lower than its control group ( ( 41.2 ±18.8 )ng/ml, P ＜ 0.05 ). No significant changes of hippocampus DA concentration were seen between these test groups and their control groups. The number of TH positive cells in substantia nigra significantly decreased in three test groups compared to their control groups( P ＜ 0.05 ). Conclusion The difference of spatial reference memory between three regimens of the mouse model of Parkinson' s disease may not due to the difference of DA level in their brain.