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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
  • Musthafa Mohamed Essa
  • Gilles J. Guillemin
  • Saravana Babu Chidambaram
ORIGINAL ARTICLE

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.

Keywords

Telmisartan AT1 receptor Astroglia Dopaminergic Motor function Chronic parkinsonism 

Notes

Acknowledgements

This project was funded by Scientific and Engineering Research Board (SERB), Project Sanction No. SB/FT/LS-293/2012, Department of Science & Technology, Govt. of India.

Authors’ Contributions

Participated in research design: Chidambaram

Conducted experiments: Sekar, Mani and Rajamani

Contributed new reagents or analytic tools: Chidambaram

Performed data analysis: Sekar, and Chidambaram

Wrote or contributed to the writing of the manuscript: Sekar, Bhat, Ray, Thamilarasan, Guillemin, Essa, Chidambaram

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Sathiya Sekar
    • 1
  • Sugumar Mani
    • 2
  • Barathidasan Rajamani
    • 3
  • Thamilarasan Manivasagam
    • 4
  • Arokiasamy Justin Thenmozhi
    • 4
  • Abid Bhat
    • 5
  • Bipul Ray
    • 5
  • Musthafa Mohamed Essa
    • 6
    • 7
  • Gilles J. Guillemin
    • 8
  • Saravana Babu Chidambaram
    • 5
  1. 1.Department of BiotechnologyDr. M.G.R. Educational and Research Institute UniversityChennaiIndia
  2. 2.Research and Development CentreBharathiar UniversityCoimbatoreIndia
  3. 3.Regional Viral Research and Diagnostic Laboratory (RVRDL), Department of MicrobiologyJIPMERPuducherryIndia
  4. 4.Department of Biochemistry and BiotechnologyAnnamalai UniversityAnnamalainagarIndia
  5. 5.Department of Pharmacology, JSS College of PharmacyJSS Academy of Higher Education and ResearchMysuruIndia
  6. 6.Department of Food Science and Nutrition, CAMSSultan Qaboos UniversityMuscatOman
  7. 7.Ageing and Dementia Research GroupSultan Qaboos UniversityMuscatOman
  8. 8.Department of Biomedical Sciences, Faculty of Medicine and Health SciencesMacquarie UniversitySydneyAustralia

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