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*

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    13 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 2018

    Bibliographical note

    Authors have identified inadvertent overlap of images in Figs.1, 2, and 5 of the article original version. The same are corrected and erratum is submitted. However, the results and conclusion on the findings remain the same. The correction can be found online at https://doi.org/10.1007/s12640-018-09921-3

    Keywords

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

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