Effects of quetiapine on the memory and the expression of doublecortin in the hippocampus of schizophrenia model mice induced by cuprizone / 中华行为医学与脑科学杂志

ABSTRACT

Objective To investigate the effect of quetiapine (QUE) on the memory and doublecortin (DCX) expression in the hippocampus of C57BL/6 mice with cuprizone (CPZ)-induced schizophrenia in C57BL/ 6 mice.Methods 1％ dimethyl sulfoxide (DMSO) was used as a vehicle to dissolve QUE.Three group of mice,16 in each of three groups,were treated with vehicle (control group),0.2％ CPZ alone (CPZ group) or 0.2％ CPZ combined with 10 mg· kg-1 · d-1 QUE (QUE+CPZ group) for six weeks,respectively.Spatial working memory was evaluated by Y-type maze test 24 hours after the completion of the treatment period.The number of DCX positivenew neurons was calculated by immunofluorescence staining assay.The expression of Notch1 and Hes1 mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) assay.Results (1) Y-maze testCPZ group achieved a much lower percentage of correct alternation than control group ((22.70±6.70) ％ vs (57.69 ±6.70)％) in Y-maze test (P＜0.05).The percentage of correct alternation in CPZ + QUE group ((54.69± 10.06) ％) was significantly increased compared with CPZ group (P＜0.01).CPZ mice exhibited significant spatial working memory impairment.(2) Immunofluorescence stainingthe number of DCX-positive cells in the hippocampus of the CPZ group (6342.85± 1801.72) was significantly decreased compared with that in control group (19428.57±2507.13) (P＜0.01),and it was reversed by QUE intervention (15928.57±2049.97).(3) RT-PCRthe Notch1 and Hes1 mRNA expression in CPZ group were significant lower than that in sham and CPZ + QUE group,(Notch1 (0.97±0.29) vs (0.23±0.20),P＜0.01);Hes1 (1.00±0.41) vs (0.38±0.30),P＜0.01),and there was no significant difference between sham group and CPZ + QUE group.Conclusion QUE is helpful to relieve CPZ-induced cognitive impairment and decreases expression of DCX in hippocampal,which may be related with activation of Notch1 pathway.