Effects of proteasome inhibitor MG132 on memory acquisition and retrieval in one-trial passive avoidance in mice

Abstract

Objective To investigate the effects of proteasome inhibitor MG132 on memory acquisition and memory retrieval in one-trail passive avoidance for mice. Methods MG132 (25 mg/kg) was administrated at different time points to analyze the time-dependent effects of MG132 on hippocampus proteasome activity. MG132 (25 mg/kg) was administrated 3 hours before-training or 1.5 hours pre-test to investigate the effect on memory acquisition and retrieval. The interaction of low dose (12 mg/kg) of MG132 and novelty interference on memory retrieval to studied. Results Hippocampus proteasome activity was significantly blocked when MG132 (25 mg/kg) was administrated 0.5-1.5 hours before analysis. The inhibition recovered as time passing and backed to normal state 24 hours later.A significant difference was showed between vehicle and pre-training, pre-test group(pre-training vehicle (296.03±3.97)s, pre-training (173.30±47.51)s; pre-test vehicle (199.23±43.01)s, pre-test (44.10±11.16)s). Proteasome inhibitor did not produce a significant effect on memory retrieval (vehicle (174.19±30.54)s, lower dose (174.19±30.54)s), then only together with a novelty task the retrieval was significantly altered(vehicle (164.02±35.26)s, MG132+ novelty group (84.70±23.92)s). Conclusion Proteasome inhibitor MG132 can inhibit memory acquisition and memory retrieval. Thereby the effect on memory retrieval is enhanced by novelty. Thus, a physiological proteasome activity is essential for learning abilities. Key words: Memory acquisition; Memory retrieval; Ubquitin-proteasome system; MG132; One-trial passive avoidance