多巴胺受体D1在小鼠运动调节方面的作用及与帕金森病的关系

目的: 探讨多巴胺受体亚型D1在小鼠运动协调中的作用及与帕金森病的关系. 方法:观察WT组(野生型)和D1(-/-)组小鼠的运动协调行为、体质量等表现差异;纹状体部苏木精伊红(HE)石蜡切片的形态学比较;酪氨酸羟化酶(TH)免疫组化黑质致密部嘴侧1/3～2/3多巴胺能神经元数目比较,以及纹状体部Western Blot蛋白水平检测TH含量变化. 结果:TH免疫组化示两组小鼠黑质致密部嘴侧1/3～2/3区域的阳性多巴胺能神经元数目无明显差异. HE染色示两组小鼠纹状体部形态及其大小无明显差别,但日常行为学观察两组小鼠差异显著(P＜0.01),D1(-/-)组小鼠中脑石蜡切片显示神经元的退行性表现;而WT组未发现典型的神经元退行性改变. Western Blot示WT组与D1(-/-)组小鼠的纹状体部TH表达水平差异显著(P＜0.05). 结论:多巴胺受体D1在小鼠运动协调方面起重要作用,该受体的缺失对黑质多巴胺能神经元的影响程度虽没临床帕金森病(PD)严重,但仍可加速多巴胺能神经元发生退行性改变.

Role of dopamine D1 receptor in mouse motor coordination and its relationship with Parkinson's disease

AIM:To understand the role of dopamine D1 receptor in mouse motor coordination,and the possible role of this gene in the etiology of Parkinson's disease.METHODS:The disparities in motor behaviors and weight of WT(wild-type)group and D1(-/-)group were assessed;and the differences in their HE histological and anti-TH(tyrosine hydroxylase)antibody immunohistochemical results were compared.The labeled cells were counted under microscope and analyzed statistically.And contents of TH of the two groups were analyzed with Western Blot.RESULTS:No obvious difference was found in HE histological result and the number of labeled cells between WT group and D1(-/-)group in substantia nigra,but the disparities in their motor behaviors and weight were significant(P<0.01).Expression of TH at protein level by Western Blot in corpus striatum between the two groups was also significant(P<0.05).Eosinophilic bodies were found in D1(-/-)group but not in WT group.CONCLUSION:Dopamine D1 receptor plays an important role in the regulation of motor coordination of mice.When this receptor has been knocked out,mice show motor dysfunction,lower weight with eosinophilic bodies in substantia nigra,and lower TH expression in corpus striatum.These abnormities are correlated to the early-middle phase of Parkinson's disease.