Different doses of sevoflurane facilitate and impair learning and memory function through activation of the ERK pathway and synthesis of ARC protein in the rat hippocampus

摘要

Highlights ? Change in Sevoflurane may stimulate and depress memory in the rats according to the dose but the cellular mechanisms of this bidirectional effect are little understood. ? We use intra-hippocampal microinfusion of U0126 to suppress the ERK activation in rats’ hippocampal neurons in vivo. 0.11%SEV led to rapid phosphorylation of ERK while 0.3%SEV inhibited it. There is a similar tendency in results of IA training. Local infusion of U0126 abolished 0.3%SEV induced memory impairment and ERK inhibition. Selective up-regulation of protein for Arc and Synapsin-1 in 0.3%SEV when compared with those in 0.11%SEV were also observed. ? Our study implies that different doses of sevoflurane trigger synaptic plasticity through ERK and selective induction of the dendritic protein species Arc. Abstract Background Sevoflurane has been shown to stimulate or depress memory in adult rats; however, the cellular mechanism of this bidirectional effect has not been fully investigated. Methods We used an intra-hippocampal microinfusion of U0126 to suppress ERK activation. Male SD rats were randomly assigned to four groups: Sham, 0.11%SEV, 0.3%SEV and 0.3%+U0126. They received bilateral injections of U0126 or saline. Rats were anesthetized, and Inhibitory Avoidance (IA) training was performed immediately after anesthesia. The memory retention latency was observed 24?h later. In another experiment, the hippocampus was removed 45?min after IA training to assess ARC expression, the synapsin 1 protein levels and the phosphorylation level of ERK. Results Treatment with 0.11%SEV led to rapid phosphorylation of ERK, while 0.3%SEV inhibited phosphorylation; the latter change was reversed by the microinfusion of U0126 in the hippocampus. The memory latency result had similar tendencies. The local infusion of U0126 abolished the 0.3%SEV-induced memory impairment and ERK inhibition. Selective upregulations of ARC and synapsin 1 proteins were observed in the 0.3%SEV group compared with the 0.11%SEV group. Conclusions The results indicate that different doses of sevoflurane trigger synaptic plasticity-related cytoskeleton proteins through the ERK signaling pathway. This novel modulation by inhalational agents may help to reduce their side-effects on memory function.