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Neuropharmacology. 2013 Oct;73:98-110. doi: 10.1016/j.neuropharm.2013.05.025. Epub 2013 Jun 6.

Telmisartan attenuates MPTP induced dopaminergic degeneration and motor dysfunction through regulation of α-synuclein and neurotrophic factors (BDNF and GDNF) expression in C57BL/6J mice.

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1
Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai 600 116, TN, India.

Abstract

Telmisartan (TEL), an angiotensin type 1 receptor (AT1R) antagonist, has been reported to exert neuroprotective effect in animal models of Parkinson's disease (PD). However, its effect on motor functions, mutant protein α-synuclein (SYN) and neurotrophic factors (BDNF and GDNF) expression and their interrelation in PD has not yet been elucidated. In the present study, the effect of TEL on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced motor dysfunctions and dopaminergic degeneration was ascertained through investigating the alterations in protein expression of dopamine transporter (DAT), tyrosine hydroxylase (TH) and SYN in C57BL/6J mouse. Further, the role of TEL on the gene expression of neurotrophic factors such as BDNF and GDNF and protein expression of vesicular monoamine transporter 2 (VMAT2) and Glial fibrillary acidic proteins (GFAP) were studied. In TEL treated mouse, strong negative correlation was observed between motor function and SYN, while a strong positive correlation was noted with BDNF and GDNF expression. TEL caused down-regulation of SYN, GFAP and up-regulation of DAT, TH, VAMT2, BDNF and GDNF expressions. Present data suggest that brain renin angiotensin system (RAS) plays a crucial role in motor function and in the regulation of key proteins such as SYN, BDNF and GDNF, DAT, TH, VMAT2 and GFAP in Parkinsonism. In conclusion, the present study shows that angiotensin type 1 receptor antagonists can ameliorate motor dysfunction and act as potential neuroprotective agent in the management of Parkinsonism.

KEYWORDS:

1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; 3,4-dihydroxyphenylacetic acid; ANOVA; AT1R; BDNF; CMC; DAT; DOPAC; GDNF; GFAP; HVA; MPTP; Motor function; PD; Parkinson's disease; RAS; Renin-angiotensin system; SEM; SNpc; ST; SYN; Striatum; TEL; TH; Telmisartan; VMAT2; analysis of variance; angiotensin type 1 receptor; brain derived neurotrophic factor; carboxy methyl cellulose; dopamine transporter; glial derived neurotrophic factor; glial fibrillary acidic proteins; homovanillic acid; i.p.; intraperitoneal; standard error of the mean; substantia nigra pars compacta; tyrosine hydroxylase; vesicular monoamine transporter 2; α-synuclein

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