β-Hydroxybutyric acid improves cognitive function in a model of heat stress by promoting adult hippocampal neurogenesis

Abstract Heat stress has multiple potential effects on the brain, such as neuroinflammation, neurogenesis defects, and cognitive impairment. β-hydroxybutyric acid (BHBA) been demonstrated to play neuroprotective roles in various models of neurological diseases. In present study, we investigated efficacy BHBA alleviating heat stress-induced impairments adult hippocampal function, well underlying mechanisms. Mice were exposed 43 ℃ for 15 min 14 days after administration with saline, BHBA, or minocycline. Here, showed first time that normalized memory ability stress-treated mice attenuated stress-impaired neurogenesis. Consistently, noticeably improved synaptic plasticity neurons by inhibiting decrease synapse-associated proteins density dendritic spines. Moreover, inhibited expression cleaved caspase-3 suppressing endoplasmic reticulum (ER) stress, increased brain-derived neurotrophic factor (BDNF) hippocampus activating protein kinase B (Akt)/cAMP response element binding (CREB) methyl-CpG 2 (MeCP2) pathways. These findings indicate is a agent improving functions mice. The action may be mediated ER Akt-CREB-BDNF MeCP2 pathways improve plasticity.