Effects of Telmisartan, an AT1 receptor antagonist, on mitochondria-specific genes expression in a mouse MPTP model of Parkinsonism

Bipul Ray, Girish Ramesh, Sudhir Rama Verma, Srinivasan Ramamurthy, Sunanda Tuladhar, Arehally Marappa Mahalakshmi, Musthafa Mohamed Essa, Saravana Babu Chidambaram*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Background: Mitochondrial dysfunction plays a crucial role in Parkinson's disease (PD) pathogenesis. The present study was undertaken to investigate the effects of Telmisartan (TEL), an angiotensin II type 1 receptor (AT1R) blocker, on the mitochondria-specific genes expression in a mouse model of Parkinsonism. Materials and methods: Mice were divided into 5 groups with 6 in each; Group I received 0.5% CMC (control) + saline, Group II received 0.5% CMC + 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) (positive control), Group III & IV received MPTP + TEL 3 and 10 mg/kg, p.o. respectively, Group V received TEL 10 mg/kg, p.o. (drug control). MPTP was given 80 mg/kg intraperitoneal in two divided doses (40 mg/kg × 2 at 16 h time interval). Vehicle or TEL was administered 1 h before the MPTP injection. Motor function was assessed 48 h after the first dose of MPTP and animals were euthanized to collect brain. Results: Mice intoxicated with MPTP showed locomotor deficits and significant upregulation of α-synuclein (α-syn), downregulation of metastasis-associated protein 1 (MTA1), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in the substantia nigra pars compacta (SNpc) and Striatum (STr) regions of brains. In addition, MPTP intoxication down-regulated mitochondria-specific genes such as DJ- 1, PTEN-induced putative kinase 1 (PINK1), Parkin, enriched with leucine repeats kinase 2 (LRRK2) gene expfression. Pre-treatment with TEL restored locomotor functions and upregulated PINK1, Parkin, LRRK2, DJ-1, MTA1 and UCHL1. Conclusion: The present study evidences that TEL has the ability to improve mitochondrial functions in PD.

Original languageEnglish
Pages (from-to)262-271
Number of pages10
JournalFrontiers in Bioscience - Landmark
Volume26
Issue number8
DOIs
Publication statusPublished - Aug 30 2021

Keywords

  • DJ-1
  • LRRK2
  • MTA1
  • Mitochondria
  • PINK1
  • Parkin
  • Parkinson's disease
  • Telmisartan
  • UCHL1
  • α-synuclein

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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