Suberoylanilide hydroxamic acid reversed cognitive and synaptic plasticity impairments induced by sevoflurane exposure in adult mice.

Although it has been shown that sevoflurane exposure could impair the cognitive function, there are few effective treatments to prevent this disorder. Suberoylanilide hydroxamic acid (SAHA), an inhibitor of histone deacetylase, plays an important role in hippocampal memory formation, which has been proven to enhance memory. As such, we explored whether SAHA could improve the memory impairment induced by sevoflurane in adult mice. In the present study, adult male C57BL/6 mice were exposed to 3% sevoflurane for 6 h, and then the cognitive impairment in Morris water maze was found at 24 h after anesthesia. Moreover, an impairment in long-term potentiation was also detected in the isolated hippocampal slices. SAHA administrated intraperitoneally 2 h before anesthesia improved cognitive and synaptic plasticity impairments. SAHA also significantly reversed the decreases in Ac-H3, brain-derived neurotrophic factor, tropomyosin-related kinase B, and p-cAMP response element-binding expressions induced by sevoflurane exposure, and reduced the level of apoptosis-related protein cleaved caspase-3. We concluded that cognitive and synaptic plasticity impairments induced by sevoflurane exposure could be reversed by normalizing the histone acetylation state. The effect is related to inhibiting cell apoptosis and activating the brain-derived neurotrophic factor/tropomyosin-related kinase B/cAMP response element-binding signaling pathway in the hippocampus.