CRH Mediate Chronic Pregnacy Stress Inducing Depression In Offspring Male Mice

Objective To explore whether the CRH mediate offspring depression induced by chronic pregnacy stress,and the possible mechanism.Methods 20-day offspring male mice as the research object and randomly devided into the control group(Control group),the chronic prenatal stress group(CPS group),and the chronic prenatal stress+CRHR1 antagonist group(CPS+ANT group).Offspring male mice depression was investigate by the open field test,sucrose preference test and forced swimming test,and the light microscope was used to examined the CA3 field histopathologic changes in the offspring male hippocampus.Additionally,the expression of m TOR in hippocampus was observed by the Western blot,and the RT-PCR was used to detecte the level of m TOR m RNA.Furthermore,ELISA was used to examine the hippocampus levels of CRH in the offspring mice.On the other hand,the brain of 7 days Sprague-Dawley rats were used,and the hippocampal slices were cultured in vitro.The experiment was divided into the control group(control group),the 1.0 μM CRH + solvent control(CRH group),the 1.0μM CRH + 0.1μM CRHR1 antagonist group(Low group),the 1.0μM CRH + 1.0μM CRHR1 antagonist group(Middle group),the 1.0 μM CRH + 10 μM CRHR1 antagonist group(High group).Western blot was used to observe the expression of m TOR in hippocampal brain tissue.Results: Compare with the Control group,the CPS group offspring mice had less motion time in forced swimming test(P<0.05)and decreased sugar preference rate in sugar preference test(P<0.05).In the open field test,the distance,the mean speed,the number of line crossings and the number of standing times were decreased(P<0.05).The neuropathological changes were characterized by the soma condensation,loosed neurons,decreased neuron number,nuclear pyknosis in the CA3 field of offspring hippocampus.Moreover,the expression of m TOR were decreased in hippocampus,and the hippocampus CRH concentration were increased(P<0.05)in CPS group.Compared with the CPS group,the offspring mice had more motion time,and the sugar preference rate was increased in the sugar preference test(P<0.05)in CPS+ANT group.In the open field test,the distance,the mean speed,the number of line crossings and the number of standing times were increased(P<0.05).The neuropathological changes were characterized by the decresed number of damaged neuron,increased neuron number in the CA3 field of hippocampus in CPS+ANT group.On the other hand,Compared with the CPS group,the expression of m TOR were increased in hippocampus,and the hippocampus CRH concentration were decreased(P<0.05).Compared with the Control group,RT-PCR experiments showed that the m RNA expression of m TOR m RNA in the hippocampus of CPS group was not significantly and the m RNA expression of m TOR m RNA in hippocampus of CPS+ANT group was significantly increased.(P<0.05).Compared with the CPS group,m TOR m RNA expression in the hippocampus of the CPS+ANT group was significantly increased(P<0.05).In vitro,Western blot analysis showed that compared with CRH group,the other four groups of hippocampal slices m TOR expression were increased(P <0.05);compared with Control group,the CRH group of hippocampal slices m TOR expression was significantly decreased(P<0.05);compared with CRH group,the Low group,Middle group and High group of hippocampal slices m TOR expression were increased(P<0.05).Conclusion CRH mediated offspring depression induced by chronic pregnacy stress,which may be related to chronic pregnacy stress increasing the level of CRH increasing in offspring hippocampus,decreasing the m TOR protein expresion and resulting in the neuron injury in the CA3 field of hippocampus.