Dexmedetomidine attenuates sleep deprivation-induced inhibition of hippocampal neurogenesis via VEGF-VEGFR2 signaling and inhibits neuroinflammation.

Long periods of sleep deprivation (SD) have serious effects on health. While the α 2 adrenoceptor agonist dexmedetomidine (DEX) can improve sleep quality for patients who have insomnia, the effect of DEX on cognition and mechanisms after SD remains elusive. C57BL/6 mice were subjected to 20 h SD daily for seven days. DEX (100 μg/kg) was administered intravenously twice daily (at 1:00 p.m. and 3:00 p.m.) during seven days of SD. We found that systemic administration of DEX attenuated cognitive deficits by performing the Y maze and novel object recognition tests and increased DCX+, SOX2+, Ki67+, and BrdU+NeuN+/NeuN+ cell numbers in the dentate gyrus (DG) region of SD mice by using immunofluorescence, western blotting, and BrdU staining. DEX did not reverse the decrease in DCX+, SOX2+, or Ki67+ cell numbers in SD mice after administration of the α 2A -adrenoceptor antagonist BRL-44408. Furthermore, the vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor 2 (VEGFR2) expression was upregulated in SD+DEX mice compared with SD mice. Luminex analysis showed that the neurogenic effects of DEX were possibly related to the inhibition of neuroinflammation, including IL-1α, IL-2, CCL5, and CXCL1. Our results suggested that DEX alleviated the impaired learning and memory of SD mice potentially by inducing hippocampal neurogenesis via the VEGF-VEGFR2 signaling pathway and by suppressing neuroinflammation, and α 2A adrenoceptors are required for the neurogenic effects of DEX after SD. This novel mechanism may add to our knowledge of DEX in the clinical treatment of impaired memory caused by SD. [Display omitted] • Dexmedetomidine ameliorates memory impairment induced by sleep deprivation. • Dexmedetomidine promotes adult hippocampal neurogenesis via the VEGF-VEGFR2 signaling pathway. • Dexmedetomidine inhibits hippocampal neuroinflammation in sleep-deprived mice. [ABSTRACT FROM AUTHOR]