Muramatsu Y, Kurosaki R, Watanabe H, Michimata M, Matsubara M, Imai Y, Araki T
Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Sendai, Japan.
J Neural Transm (Vienna). 2003 Oct;110(10):1129-44. doi: 10.1007/s00702-003-0021-y.
We investigated the immunohistochemical alterations of neuronal nitric oxide synthase (nNOS), endothelial NOS (eNOS), tyrosine hydroxylase (TH), microtubule-associated protein 2a,b (MAP 2), glial fibrillary acidic protein (GFAP), parvalbumin (PV), and dopamine transporter (DAT) in the striatum and substantia nigra following the application of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice. TH-, MAP 2- and DAT-immunoreactive cells were decreased gradually in the striatum and substantia nigra from 1 day up to 7 days after MPTP treatment, as well as the reduction of the striatal dopamine, DOPAC and HVA content. The number of GFAP-immunoreactive astrocytes increased gradually in the striatum and substantia nigra from 1 day up to 7 days after MPTP treatment. Striatal nNOS-immunoreactive cells were unchanged in MPTP-treated mice. In the substantia nigra, intense immunoreactivity of nNOS-positive cells increased 5 hr after MPTP treatment. Thereafter, the immunoreactivity of nNOS-positive cells decreased gradually from 1 day up to 7 days after MPTP treatment. eNOS-immunopositive cells were unchanged in the striatum and substantia nigra. These results demonstrate that nNOS may play a key role in the development of MPTP neurotoxicity. Our findings also indicate that MPTP can cause the functional damage of interneurons in the substantia nigra, but not in the striatum.
我们研究了小鼠应用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）后纹状体和黑质中神经元型一氧化氮合酶（nNOS）、内皮型一氧化氮合酶（eNOS）、酪氨酸羟化酶（TH）、微管相关蛋白2a、b（MAP 2）、胶质纤维酸性蛋白（GFAP）、小白蛋白（PV）和多巴胺转运体（DAT）的免疫组化改变。MPTP处理后1天至7天，纹状体和黑质中TH、MAP 2和DAT免疫反应性细胞逐渐减少，同时纹状体多巴胺、3,4-二羟基苯乙酸（DOPAC）和高香草酸（HVA）含量也降低。MPTP处理后1天至7天，纹状体和黑质中GFAP免疫反应性星形胶质细胞数量逐渐增加。MPTP处理的小鼠纹状体nNOS免疫反应性细胞无变化。在黑质中，MPTP处理5小时后nNOS阳性细胞的强烈免疫反应性增加。此后，MPTP处理后1天至7天，nNOS阳性细胞的免疫反应性逐渐降低。纹状体和黑质中eNOS免疫阳性细胞无变化。这些结果表明，nNOS可能在MPTP神经毒性的发展中起关键作用。我们的研究结果还表明，MPTP可导致黑质中间神经元的功能损伤，但不会导致纹状体中间神经元的功能损伤。
