Olha Yu. Harmatina; Kateryna V. Rozova; Maryna I. Vasylenko; Tetiana Yu. Lapikova-Bryhinska; Maria V. Belikova & Alla G. Portnychenko

Hypoxic preconditioning is known to induce neuroprotection, but its effects and pathways in chronic brain pathology still unknown. The aim was to establish an involvement of a7 subunit of nicotinic acetylcholine receptors (a7nAchRs), and sirtuins of 1 (SIRT1) and 3 (SIRT3) types in the effects of hypoxic hypobaric preconditioning on brain damage in mice with chronic cerebral hypoperfusion caused by the left common carotid artery occlusion. The male C57/6j (C57, wild type) and a7nAchRs(-/-) mice were divided to six experimental groups (10 mice per group): sham-operated C57, C57 with chronic cerebral hypoperfusion, C57 with hypoxic hypobaric preconditioning and chronic cerebral hypoperfusion, sham-operated a7nAchRs(-/-) mice, a7nAchRs(-/-) with chronic cerebral hypoperfusion, a7nAchRs(-/-) with hypoxic hypobaric preconditioning and chronic cerebral hypoperfusion. For preconditioning, mice were exposed to hypoxia by “lifting” in barochamber to simulated altitude of 5600 m a.s.l. for 1 h/day on 3 consecutive days before surgical manipulation. Expressions of SIRT1, SIRT3 in brain tissue, and histopathological changes of the hippocampi were examined. It was shown that 8-week chronic hypoperfusion of the brain, caused by unilateral occlusion of the common carotid artery, was accompanied by injury to the neurons of the hippocampi of both hemispheres, which was more pronounced on the side of the occlusion. This damage, as well as the mechanisms of neuroprotection induced by hypoxic preconditioning, were maintained for at least 8 weeks by mechanisms mediated through a7nAChRs. Deficite of a7nAChRs was accompanied with reduction of neuronal damage caused CCH in 8 weeks, as well as preconditioning effects, and lead to compensatory activation of regulatory and protective mechanisms mediated by SIRT1, in normal conditions and in CCH. In wild-type (C57) mice, protective mechanisms in CCH were realized to a greater extent by increased expression of SIRT3 in both hemispheres of the brain.

KEY WORDS: Hypoxic hypobaric preconditioning; Unilateral common carotid artery occlusion, Chronic cerebral hypoperfusion; a7nAchRs(-/-) mice; SIRT1; SIRT3

HARMATINA, O. Y.; ROZOVA, K. V.; VASYLENKO, M. I.; LAPIKOVA-BRYHINSKA, T. Y.; BELIKOVA, M. V. & PORTNYCHENKO, A. G. Involvement of SIRT1 and SIRT3 in effects of hypoxic hypobaric preconditioning on hippocampal damage induced by chronic cerebral hypoperfusion in C57/6j and a7nAchRs(-/-) mice. Int. J. Morphol., 42(3):594-600, 2024.