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.
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Change history
15 December 2019
A Correction to this paper has been published: https://doi.org/10.1007/s12640-019-00127-6
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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.
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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
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Sekar, S., Mani, S., Rajamani, B. et al. Telmisartan Ameliorates Astroglial and Dopaminergic Functions in a Mouse Model of Chronic Parkinsonism. Neurotox Res 34, 597–612 (2018). https://doi.org/10.1007/s12640-018-9921-3
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DOI: https://doi.org/10.1007/s12640-018-9921-3