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Mitochondrial Antioxidant SkQ1 Affects the GABAergic but Not the Glutamatergic System in the Hippocampus of Wistar and Senescence Accelerated OXYS Rats

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Abstract

Numerous studies have shown that mitochondria-targeted antioxidant SkQ1 can increase the lifespan of many species and suppress the development of various age-related diseases. Previously we demonstrated that SkQ1 suppresses all manifestations of accelerated senescence in OXYS rats, including the development of the main signs of Alzheimer’s disease (AD). GABA and glutamate are two of the most abundant neurotransmitters in the central nervous system, and it was showed that changes in their signaling accompany aging and the development of AD. Previously, we showed delicate age-related changes of the components of glutamate/GABA system in Wistar and OXYS rats, a unique model of AD. Here we investigated the influence of the treatment with SkQ1 from 12 through 18 months of age (that is, during the active progression of AD-like pathology) on glutamate/GABA system in the rat hippocampus. Our data demonstrated that the neuroprotective effects of long-term administration of SkQ1 are mediated by its effect on the GABAergic but not the glutamatergic system in the hippocampus of Wistar and OXYS rats. Western blotting revealed an increase in the level of glutamate decarboxylase GAD67 in rats of both strains, a decrease in the GABA transporter GAT1 in Wistar rats, and a tendency towards abrogation of the increased level of GABA receptor subunits GABAAr1 in OXYS rats. Thus, we showed that the neuroprotective effects of long-term treatment with SkQ1 are mediated by its effect on the GABAergic but not the glutamatergic system in the hippocampus of Wistar and OXYS rats.

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ACKNOWLEDGMENTS

SkQ1 was kindly provided by Maxim Skulachev from the Institute of Mitoengineering at Moscow State University (Moscow, Russia).

Funding

This research has been supported by Project FWNR-2022-0016.

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Authors and Affiliations

  1. Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences, 630090, Novosibirsk, Russia

    D. V. Telegina & N. G. Kolosova

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  1. D. V. Telegina
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  2. N. G. Kolosova
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Correspondence to D. V. Telegina.

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ETHICS APPROVAL AND CONSENT TO PARTICIPATE

The study was conducted according to Directive 2010/63/EU of the European Parliament and of the European Council of September 22, 2010 and was approved by the Commission on Bioethics at the Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences (decision # 85/1 of June 18, 2021), Novosibirsk, Russia.

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Telegina, D.V., Kolosova, N.G. Mitochondrial Antioxidant SkQ1 Affects the GABAergic but Not the Glutamatergic System in the Hippocampus of Wistar and Senescence Accelerated OXYS Rats. Adv Gerontol 13, 36–43 (2023). https://doi.org/10.1134/S2079057024600058

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