RESUMO
Objective:To establish neurodevelopmental mice model of schizophrenia(SZ) with prepulse inhibition(PPI) deficits and investigate the effectiveness of olanzapine on PPI disruption.Methods:On the 9th day of pregnancy of SPF grade C57BL/6 mice, female mice were injected with polyinosinic acid poly (I∶C) (6 mg/kg) through tail vein for immune stimulation. The stress model was constructed by chronic unpredictable mild stress 30-40 d after birth (PND30-40). The offspring mice were divided into pregnancy immune stimulation + adolescent stress group (P + S + group), pregnancy immune stimulation group (P + S- group), adolescent stress group (P-S+ group) and non stimulation group (P-S-group), with 18 mice in each group. The mice in P+ S+ group were divided into OLZ intervention group (OLZ group) and non-OLZ intervention group (non-OLZ group), with 9 mice in each group. The PPI function of mice was detected by acoustic startle reflex test after modeling and OLZ intervention. Adopt StatView Version 5.0 software for data analysis, and multi factors analysis of variance was used to test the main effect, interactive effect and simple effect of each factor.Results:The main effects of maternal Poly(I: C) immune activation and pubertal chronic unpredictable stress were significant( F(1, 330)=47.72, P<0.01), and there was a significant interaction between the two factors( F(1, 330)=14.80, P<0.01), simple effect analysis showed that average percent prepulse inhibition (PPI%) in P+ S+ group((15.42±6.13)%) was significantly decreased compared with groups of P+ S-((27.33±4.58)%), P-S+ ((31.17±3.97)%) and P-S-((47.14±12.28)%)(all P<0.01). There was significant gender difference in Prepulse inhibition(PPI)score( F(1, 396)=61.94, P<0.01), in male and female mice, average startle reactivity of Pulse under Prepulse+ Pulse influence of distinct intensities was significantly different( F(1, 198)=18.68, 18.44, P<0.01), and the maternal Poly(I∶C) immune activation had a significant main effect( F(1, 198)=32.18, 12.58, P<0.01) and interaction with pubertal chronic unpredictable stress( F(1, 198)=34.54, 11.39, P<0.01), simple effect analysis suggested that the average startle reactivity of Prepulse+ Pulse in P+ S+ group(0.47±0.12) was significantly higher than other three groups(P+ S-: 0.36±0.11, P-S+ : (0.25±0.22), P-S-: (0.31±0.19)) in male mice( P<0.01) and in P-S+ group was significantly higher than the other three groups in female mice ( P<0.01). OLZ treatment could efficiently reverse the deficits on PPI by increasing PPI%( F(1, 165)=18.24, P<0.01), OLZ could reduce PPI score in male "dual-hit" model mice( F(1, 102)=21.81, P<0.01)and raise it in female( F(1, 102)=4.88, P<0.05). Conclusion:OLZ can reverse PPI deficits in schizophrenic neurodevelopmental model mice, and in the evaluation of PPI function in the model mice through PPI of acoustic startle reflex, PPI% has better stability and reactivity to OLZ intervention.