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

Research output: Contribution to journalArticle

2 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

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Angiotensin Type 1 Receptor
Parkinsonian Disorders
Parkinson Disease
Vesicular Monoamine Transport Proteins
Angiotensin II Type 1 Receptor Blockers
1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
Dopamine Plasma Membrane Transport Proteins
Glial Fibrillary Acidic Protein
Nerve Growth Factors
Tyrosine 3-Monooxygenase
Neuroprotective Agents
Nitric Oxide Synthase Type II
Inbred C57BL Mouse
Neuroglia
Glutathione
Dopamine
Nitric Oxide
Chronic Disease
Up-Regulation
Down-Regulation

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Sekar, S., Mani, S., Rajamani, B., Manivasagam, T., Thenmozhi, A. J., Bhat, A., ... 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

Telmisartan Ameliorates Astroglial and Dopaminergic Functions in a Mouse Model of Chronic Parkinsonism. / Sekar, Sathiya; Mani, Sugumar; Rajamani, Barathidasan; Manivasagam, Thamilarasan; Thenmozhi, Arokiasamy Justin; Bhat, Abid; Ray, Bipul; Essa, Mohamed Musthafa; Guillemin, Gilles J.; Chidambaram, Saravana Babu.

In: Neurotoxicity Research, Vol. 34, No. 3, 01.10.2018, p. 597-612.

Research output: Contribution to journalArticle

Sekar, S, Mani, S, Rajamani, B, Manivasagam, T, Thenmozhi, AJ, Bhat, A, Ray, B, Essa, MM, Guillemin, GJ & Chidambaram, SB 2018, 'Telmisartan Ameliorates Astroglial and Dopaminergic Functions in a Mouse Model of Chronic Parkinsonism', Neurotoxicity Research, vol. 34, no. 3, pp. 597-612. https://doi.org/10.1007/s12640-018-9921-3
Sekar, Sathiya ; Mani, Sugumar ; Rajamani, Barathidasan ; Manivasagam, Thamilarasan ; Thenmozhi, Arokiasamy Justin ; Bhat, Abid ; Ray, Bipul ; Essa, Mohamed Musthafa ; Guillemin, Gilles J. ; Chidambaram, Saravana Babu. / Telmisartan Ameliorates Astroglial and Dopaminergic Functions in a Mouse Model of Chronic Parkinsonism. In: Neurotoxicity Research. 2018 ; Vol. 34, No. 3. pp. 597-612.
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