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

• Published in: Advances in gerontology Vol. 13; no. 1; pp. 36 - 43
• Main Authors: Telegina, D. V., Kolosova, N. G.
• Format: Journal Article
• Language: English
• Published: Moscow Pleiades Publishing 01.03.2023; Springer Nature B.V
• Subjects: Age; Aging; Antibodies; Disease; Enzymes; Geriatrics/Gerontology; Laboratory animals; Medicine; Medicine & Public Health; Proteins; Senescence; Variance analysis; United States > US; GABA; Alzheimer’s disease; hippocampus; senescence accelerated OXYS rats; glutamate; SkQ1
• ISSN: 2079-0570; 2079-0589
• DOI: 10.1134/S2079057024600058

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.