Effects of Fisetin on Cognitive Impairment in Schizophrenia Model Rats
Objective To investigate the effects of Fisetin on cognition impairment in schizo-phrenia model rats induced by dizocilpine(MK-801).Methods 24 Sprague Dawley(SD)rats were randomly divided into three groups(n=8):schizophrenia group(Group SZ),Fisetin group(Group Fisetin)and control group(Group C).Group SZ and Group Fisetin were induced by MK-801 to es-tablish the schizophrenia models.After modeling was completed,Group Fisetin was treated with Fisetin(20 mg·kg-1·d-1)by intraperitoneal injection,and Group SZ and Group C were injected intraperitoneally with an equal volume of Dimethyl sulfoxide for 14 consecutive days.Learning and memory functions of rats were evaluated with the Morris water maze assay;the protein expres-sion and phosphorylation levels of calcium/calmodulin-dependent protein kinase Ⅱ(CaMK Ⅱ),extracellular regulated protein kinase(ERK1/2)and cAMP-response element binding protein(CREB)were detected in hippocampus of rats by Western-blot.Results The results of Morris water maze showed that compared with Group C,the escape latency of Group SZ was significantly increased(P＜0.05),the space exploration time was significantly decreased(P＜0.01),and the times of traversing the location of the original safety platform was significantly reduced(P＜0.01).Compared with Group SZ,the escape latency of Group Fisetin was significantly decreased(P＜0.05),the space exploration time was significantly increased(P＜0.05),and the times of traversing the location of original safety platform was significantly increased(P＜0.05).In terms of protein expression,there were no significant differences in the expression levels of CaMK Ⅱ,ERK1/2 and CREB in hippocampal tissues of the three groups of rats(P＞0.05).The phosphoryl-ation levels of CaMK Ⅱ,ERK1/2,and CREB in Group SZ were significantly lower compared with those of Group Control(P＜0.05 or P＜0.01);and compared with those of Group SZ,the phos-phorylation levels of CaMK Ⅱ,ERK1/2,and CREB were significantly higher in Group Fisetin(P＜0.01).Conclusion Fisetin can alleviate MK-801-induced cognitive impairment in schizophre-nia model rats,and the mechanism may be related to increased phosphorylation levels of CaMKⅡ,ERK1/2 and CREB.
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