Telmisartan Ameliorates Astroglial and Dopaminergic Functions in a Mouse Model of Chronic Parkinsonism

Sathiya Sekar, Sugumar Mani, Barathidasan Rajamani, Thamilarasan Manivasagam, Arokiasamy Justin Thenmozhi, Abid Bhat, Bipul Ray, Mohamed Musthafa Essa, Gilles J. Guillemin, Saravana Babu Chidambaram*

*Corresponding author for this work

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)597-612
Number of pages16
JournalNeurotoxicity Research
Volume34
Issue number3
DOIs
Publication statusPublished - Oct 1 2018

Keywords

  • Astroglia
  • AT1 receptor
  • Chronic parkinsonism
  • Dopaminergic
  • Motor function
  • Telmisartan

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

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    Sekar, S., Mani, S., Rajamani, B., Manivasagam, T., Thenmozhi, A. J., Bhat, A., Ray, B., Essa, M. M., Guillemin, G. J., & Chidambaram, S. B. (2018). Telmisartan Ameliorates Astroglial and Dopaminergic Functions in a Mouse Model of Chronic Parkinsonism. Neurotoxicity Research, 34(3), 597-612. https://doi.org/10.1007/s12640-018-9921-3