Role of hippocampal nNOS-PSD95 coupling in short-term memory retrieval disorder induced by sevoflurane in mice

Abstract

Objective To evaluate the role of hippocampal neuronal nitric oxide synthase (nNOS)-postsynaptic dense protein 95 (PSD95) coupling in short-term memory retrieval disorder induced by sevoflurane in mice. Methods Sixteen clean-grade healthy Kunming mice of both sexes, aged 2-3 months, weighing 30-35 g, were divided into 2 groups (n=8 each) according to the random number table method: sevoflurane group (S group) and nNOS-PSD95 uncoupling agent ZL006 group (Z group). After successful establishment of dark avoidance memory, 3.3% sevoflurane and 40% O2 were inhaled for 2 h in both groups, and normal saline 1.5 ml was intraperitoneally injected in group S and ZL006 1 mg/kg in group Z at 30 min before anesthesia.The step-through latency and error times were recorded before anesthesia and at 12 h after the end of anesthesia.The mice were then sacrificed, and hippocampal tissues were taken for determination of the expression of nNOS and PSD95 (by Western blot) and co-expression of nNOS and PSD95 (by immunoprecipitation). Results Compared with that before anesthesia, the step-through latency was significantly shortened, and the error times were increased at 12 h after anesthesia in group S (P 0.05). Compared with group S, the step-through latency was significantly prolonged, error times were decreased, the co-expression of nNOS and PSD95 was down-regulated (P 0.05). Conclusion The mechanism by which sevoflurane induces short-term memory retrieval disorder may be related to promoting the coupling of nNOS to PSD95 in the hippocampus of mice. Key words: Anesthetics, inhalation; Memory disorders; Nitric oxide synthase typeⅠ; Membrane proteins