Department of Biotechnology, Dr. M.G.R. Educational and Research Institute University, Chennai, Tamilnadu, India.
Research and Development Centre, Bharathiar University, Coimbatore, TN, India.
Neurotox Res. 2018 Oct;34(3):597-612. doi: 10.1007/s12640-018-9921-3. Epub 2018 Jul 13.
Many studies reported the neuroprotective effects of angiotensin II type 1 receptor (AT1R) antagonists in Parkinson's disease (PD). However, the role of AT1R blockade on astroglial, in turn, dopaminergic functions in chronic PD is still to be studied. In the present study, telmisartan (TEL; 3 and 10 mg/kg/day; p.o), was used to study the effects AT1R blockade on astrocytic and dopaminergic functions in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinsonism (250 mg/kg, i.p, in 10 equally divided doses at 3.5 days interval) in C57BL/6 J mice. TEL significantly downregulated glial fibrillary acidic protein (GFAP), inducible nitric oxide synthase (iNOS), TNFα and IL1β expressions and nitric oxide (NO) content. Significant upregulation glial cell derived neurotrophic factor (GDNF) expression and increased glutathione (GSH) content reveal the ameliorating effects of TEL on astroglial functions. On the other hand, TEL upregulated tyrosine hydroxylase (TH), dopamine transporter (DAT), and vesicular monoamine transporter 2 (VMAT2) expressions. Finally, TEL improved dopamine and its turnover and restored locomotor performance. Present experiment reveals that TEL has the potential to alleviate astroglial functions, apart from restoring dopaminergic functions, at least in part. To conclude, TEL may be a better disease-modifying therapeutic regimen in the management of Parkinsonism, acting primarily via astroglial-dopaminergic functions.
许多研究报告称，血管紧张素 II 型 1 型受体（AT1R）拮抗剂在帕金森病（PD）中有神经保护作用。然而，AT1R 阻断对慢性 PD 中星形胶质细胞、继而对多巴胺能功能的作用仍有待研究。在本研究中，替米沙坦（TEL；3 和 10mg/kg/天；口服）用于研究 AT1R 阻断对慢性 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）帕金森病小鼠模型（250mg/kg，腹腔注射，在 3.5 天间隔的 10 等分剂量）中星形胶质细胞和多巴胺能功能的影响。TEL 显著下调胶质纤维酸性蛋白（GFAP）、诱导型一氧化氮合酶（iNOS）、TNFα 和 IL1β 的表达和一氧化氮（NO）含量。GDNF 表达的显著上调和 GSH 含量的增加表明 TEL 对星形胶质细胞功能有改善作用。另一方面，TEL 上调酪氨酸羟化酶（TH）、多巴胺转运体（DAT）和囊泡单胺转运体 2（VMAT2）的表达。最后，TEL 改善了多巴胺及其周转率，并恢复了运动表现。目前的实验表明，TEL 具有缓解星形胶质细胞功能的潜力，除了恢复多巴胺能功能外，至少在一定程度上是这样。总之，TEL 可能是帕金森病管理中一种更好的疾病修饰治疗方案，主要通过星形胶质细胞-多巴胺能功能发挥作用。
