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

• Published in: Neuropharmacology Vol. 73; pp. 98 - 110
• Main Authors: Sathiya, Sekar, Ranju, Vijayan, Kalaivani, Periyathambi, Priya, Raju Jyothi, Sumathy, Haridass, Sunil, Adoor Gopalan, Babu, Chidambaram Saravana
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.10.2013
• Subjects: alpha-Synuclein - metabolism; Angiotensin II Type 1 Receptor Blockers - pharmacology; Angiotensin II Type 1 Receptor Blockers - therapeutic use; Animals; BDNF; Behavior, Animal - drug effects; Benzimidazoles - pharmacology; Benzimidazoles - therapeutic use; Benzoates - pharmacology; Benzoates - therapeutic use; Brain-Derived Neurotrophic Factor - biosynthesis; Corpus Striatum - drug effects; Corpus Striatum - metabolism; Dopamine - metabolism; Dopamine Plasma Membrane Transport Proteins - metabolism; Gait - drug effects; GDNF; Gene Expression - drug effects; Glial Cell Line-Derived Neurotrophic Factor - biosynthesis; Glial Fibrillary Acidic Protein - biosynthesis; Male; Mice; Mice, Inbred C57BL; Motor function; MPTP; Nerve Degeneration - chemically induced; Nerve Degeneration - drug therapy; Nerve Degeneration - metabolism; Neuroprotective Agents - pharmacology; Neuroprotective Agents - therapeutic use; Parkinsonian Disorders - drug therapy; Parkinsonian Disorders - metabolism; Substantia Nigra - drug effects; Substantia Nigra - metabolism; Telmisartan; Tyrosine 3-Monooxygenase - metabolism; Vesicular Monoamine Transport Proteins - biosynthesis; α-synuclein; ST; DOPAC; BDNF; RAS; SNpc; SYN; AT1R; i.p; Telmisartan; GFAP; HVA; GDNF; PD; TH; ANOVA; DAT; VMAT2; CMC; TEL; SEM; MPTP; Motor function; α-synuclein; angiotensin type 1 receptor; brain derived neurotrophic factor; Parkinson's disease; 3,4-dihydroxyphenylacetic acid; homovanillic acid; Striatum; analysis of variance; glial derived neurotrophic factor; glial fibrillary acidic proteins; intraperitoneal; vesicular monoamine transporter 2; Renin-angiotensin system; tyrosine hydroxylase; substantia nigra pars compacta; dopamine transporter; 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine; carboxy methyl cellulose; standard error of the mean
• ISSN: 0028-3908; 1873-7064
• DOI: 10.1016/j.neuropharm.2013.05.025

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. •TEL improved motor function may be through SYN and neurotrophic factors regulation.•It also regulates astrocytic function by suppressing GFAP expression in MPTP mice.•Thus, TEL exerts neuroprotection against MPTP intoxication in C57BL/6J mice brain.