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

doi:10.1007/s12640-018-9921-3

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 journal › Article › peer-review

19 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 language	English
Pages (from-to)	597-612
Number of pages	16
Journal	Neurotoxicity Research
Volume	34
Issue number	3
DOIs	https://doi.org/10.1007/s12640-018-9921-3
Publication status	Published - 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

Access to Document

10.1007/s12640-018-9921-3

Cite this

@article{9dba710bf8c14bde81c567f47bd16408,

title = "Telmisartan ameliorates astroglial and dopaminergic functions in a mouse model of chronic Parkinsonism",

abstract = "Many studies reported the neuroprotective effects of angiotensin II type 1 receptor (AT1R) antagonists in Parkinson{\textquoteright}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 = "Astroglia, AT1 receptor, Chronic parkinsonism, Dopaminergic, Motor function, Telmisartan",

author = "Sathiya Sekar and Sugumar Mani and Barathidasan Rajamani and Thamilarasan Manivasagam and Thenmozhi, {Arokiasamy Justin} and Abid Bhat and Bipul Ray and Essa, {Musthafa Mohamed} and Guillemin, {Gilles J.} and Chidambaram, {Saravana Babu}",

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",

year = "2018",

month = oct,

doi = "10.1007/s12640-018-9921-3",

language = "English",

volume = "34",

pages = "597--612",

journal = "Neurotoxicity Research",

issn = "1029-8428",

publisher = "Springer, Springer Nature",

number = "3",

}

TY - JOUR

T1 - Telmisartan ameliorates astroglial and dopaminergic functions in a mouse model of chronic Parkinsonism

AU - Sekar, Sathiya

AU - Mani, Sugumar

AU - Rajamani, Barathidasan

AU - Manivasagam, Thamilarasan

AU - Thenmozhi, Arokiasamy Justin

AU - Bhat, Abid

AU - Ray, Bipul

AU - Essa, Musthafa Mohamed

AU - Guillemin, Gilles J.

AU - Chidambaram, Saravana Babu

N1 - 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

PY - 2018/10

Y1 - 2018/10

N2 - 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.

AB - 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.

KW - Astroglia

KW - AT1 receptor

KW - Chronic parkinsonism

KW - Dopaminergic

KW - Motor function

KW - Telmisartan

UR - http://www.scopus.com/inward/record.url?scp=85049866219&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/record.url?scp=85076474656&partnerID=8YFLogxK

U2 - 10.1007/s12640-018-9921-3

DO - 10.1007/s12640-018-9921-3

M3 - Article

C2 - 30006683

AN - SCOPUS:85049866219

SN - 1029-8428

VL - 34

SP - 597

EP - 612

JO - Neurotoxicity Research

JF - Neurotoxicity Research

IS - 3

ER -

Telmisartan ameliorates astroglial and dopaminergic functions in a mouse model of chronic Parkinsonism

Abstract

Bibliographical note

Keywords

Access to Document

Other files and links

Fingerprint

Cite this