PMID- 23747572 OWN - NLM STAT- MEDLINE DCOM- 20140813 LR - 20181202 IS - 1873-7064 (Electronic) IS - 0028-3908 (Linking) VI - 73 DP - 2013 Oct TI - Telmisartan attenuates MPTP induced dopaminergic degeneration and motor dysfunction through regulation of alpha-synuclein and neurotrophic factors (BDNF and GDNF) expression in C57BL/6J mice. PG - 98-110 LID - S0028-3908(13)00239-6 [pii] LID - 10.1016/j.neuropharm.2013.05.025 [doi] AB - 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 alpha-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. CI - Copyright (c) 2013 Elsevier Ltd. All rights reserved. FAU - Sathiya, Sekar AU - Sathiya S AD - Centre for Toxicology and Developmental Research (CEFT), Sri Ramachandra University, Chennai 600 116, TN, India. FAU - Ranju, Vijayan AU - Ranju V FAU - Kalaivani, Periyathambi AU - Kalaivani P FAU - Priya, Raju Jyothi AU - Priya RJ FAU - Sumathy, Haridass AU - Sumathy H FAU - Sunil, Adoor Gopalan AU - Sunil AG FAU - Babu, Chidambaram Saravana AU - Babu CS LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130606 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Angiotensin II Type 1 Receptor Blockers) RN - 0 (Benzimidazoles) RN - 0 (Benzoates) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Dopamine Plasma Membrane Transport Proteins) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (Neuroprotective Agents) RN - 0 (Slc18a2 protein, mouse) RN - 0 (Vesicular Monoamine Transport Proteins) RN - 0 (alpha-Synuclein) RN - EC 1.14.16.2 (Tyrosine 3-Monooxygenase) RN - U5SYW473RQ (Telmisartan) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Angiotensin II Type 1 Receptor Blockers/pharmacology/therapeutic use MH - Animals MH - Behavior, Animal/drug effects MH - Benzimidazoles/*pharmacology/therapeutic use MH - Benzoates/*pharmacology/therapeutic use MH - Brain-Derived Neurotrophic Factor/*biosynthesis MH - Corpus Striatum/drug effects/metabolism MH - Dopamine/metabolism MH - Dopamine Plasma Membrane Transport Proteins/metabolism MH - Gait/drug effects MH - Gene Expression/drug effects MH - Glial Cell Line-Derived Neurotrophic Factor/*biosynthesis MH - Glial Fibrillary Acidic Protein/biosynthesis MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Nerve Degeneration/chemically induced/drug therapy/*metabolism MH - Neuroprotective Agents/*pharmacology/therapeutic use MH - Parkinsonian Disorders/drug therapy/*metabolism MH - Substantia Nigra/drug effects/metabolism MH - Telmisartan MH - Tyrosine 3-Monooxygenase/metabolism MH - Vesicular Monoamine Transport Proteins/biosynthesis MH - alpha-Synuclein/*metabolism OTO - NOTNLM OT - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine OT - 3,4-dihydroxyphenylacetic acid OT - ANOVA OT - AT1R OT - BDNF OT - CMC OT - DAT OT - DOPAC OT - GDNF OT - GFAP OT - HVA OT - MPTP OT - Motor function OT - PD OT - Parkinson's disease OT - RAS OT - Renin-angiotensin system OT - SEM OT - SNpc OT - ST OT - SYN OT - Striatum OT - TEL OT - TH OT - Telmisartan OT - VMAT2 OT - analysis of variance OT - angiotensin type 1 receptor OT - brain derived neurotrophic factor OT - carboxy methyl cellulose OT - dopamine transporter OT - glial derived neurotrophic factor OT - glial fibrillary acidic proteins OT - homovanillic acid OT - i.p. OT - intraperitoneal OT - standard error of the mean OT - substantia nigra pars compacta OT - tyrosine hydroxylase OT - vesicular monoamine transporter 2 OT - alpha-synuclein EDAT- 2013/06/12 06:00 MHDA- 2014/08/15 06:00 CRDT- 2013/06/11 06:00 PHST- 2013/02/17 00:00 [received] PHST- 2013/04/18 00:00 [revised] PHST- 2013/05/27 00:00 [accepted] PHST- 2013/06/11 06:00 [entrez] PHST- 2013/06/12 06:00 [pubmed] PHST- 2014/08/15 06:00 [medline] AID - S0028-3908(13)00239-6 [pii] AID - 10.1016/j.neuropharm.2013.05.025 [doi] PST - ppublish SO - Neuropharmacology. 2013 Oct;73:98-110. doi: 10.1016/j.neuropharm.2013.05.025. Epub 2013 Jun 6.