The influence of Mexidol on cerebral mitochondriogenesis at a young age and with aging

Authors:
KIROVA Yu.I. 1*, SHAKOVA F.M. 1*, GERMANOVA E.L. 1*, ROMANOVA G.A. 1*, VORONINA T.A. 2*

1* Federal State Budgetary Scientific Institution "Research Institute of General Pathology and Pathophysiology", Moscow, Russia;
2* Federal State Budgetary Scientific Institution "V.V. Zakusov Research Institute of Pharmacology", Moscow, Russia

Place of publication:S.S. Korsakov Journal of Neurology and Psychiatry / Vol. 120, No. 1, 2020

Resume

The aim of the study. To study the ability of the drug Mexidol to induce cerebral mitochondriogenesis in the brain of young and aging rats.
Material and methods. The expression level of protein markers of cerebral mitochondriogenesis was assessed in the cerebral cortex of young (3 months; n=216) and aging (6, 9, 12 and 15 months; n=168) outbred male rats using Western blot analysis during a course of treatment with Mexidol (20, 40, 100 mg/kg; 20 days; intraperitoneally).
Results. For the first time, it was shown that Mexidol administered repeatedly at doses of 40 and 100 mg/kg resulted in a dose-dependent induction of the succinate receptor SUCNR1 and mitochondrial biogenesis marker proteins: the transcriptional coactivator PGC-1α, transcription factors (NRF1, TFAM), catalytic subunits of respiratory enzymes (NDUFV2, SDHA, cyt b, COX2), and ATP synthase (ATP5A) in the cerebral cortex of young and aging outbred male rats. Mexidol-dependent overexpression of mitochondrial enzyme subunits and PGC-1α was observed only with repeated administration of the drug.
Conclusion. The obtained data indicate the ability of Mexidol to induce cerebral mitochondriogenesis and eliminate mitochondrial dysfunction in young and aging animals and, thus, influence one of the key pathogenetic links in the development of disorders during aging and neurodegenerative diseases.

Key words: aging, mitochondrial dysfunction, Mexidol, succinate receptor, cerebral mitochondriogenesis
, transcriptional coactivator PGC-1α

Information about the authors:
Kirova Yu.I. - https://orcid.org/0000-0002-2436-3661; e-mail: bioenerg@mail.ru
Shakova F.M. - https://orcid.org/0000-0002-0494-2500; e-mail: shakova.fatima@yandex.ru
Germanova E.L. - https://orcid.org/0000-0003-1191-8477; e-mail: elgerm@mail.ru
Romanova G.A. - https://orcid.org/0000-0003-0090-351X; e-mail: romanovaga@mail.ru
Voronina T.A. - https://orcid.org/0000-0001-7065-469X; voroninata38@gmail.com

How to cite:
Kirova Yu.I., Shakova F.M., Germanova E.L., Romanova G.A., Voronina T.A. The effect of Mexidol on cerebral mitochondriogenesis
at a young age and during aging. Korsakov Journal of Neurology and Psychiatry. 2020;120(1):55–62.
https://doi.org/10.17116/jnevro202012001155