The Influence Of Prenatal Stress On Offspring Behaviors And Brain Myelin Developmentin Mice

Objective The etiology of major depression(MDD) is complex. Accumulated evidence suggests that exposure to stressful life events during pregnancy exerts profound effects on neurodevelopment and increases the risk for several neuro-developmental disorders including major depression, bipolar disorder, schizophrenia and autism in adulthood. In order to explore pathophysiology of MDD, we used established prenatal restraint stress(PRS) model, to observe PRS induced MDD related behavioral deficits in offspring mice at different growth periods.In addition, to explore whether MDD-like behavior induced by PRS is associated with alteration of myelin, we examined myelin development and related genes.Methods The Kunming mice were used in this project. The pregnant dam were randomly divided into 2 groups: blank control group(No Stress, NS) and prenatal restraint stress group(PRS),in which NS group did not receive any stress, while PRS group received a regular restraint stress from the seventh day of gestation to delivery. We selected offspring at the age of postnatal day PND30、PND50、PND60, for following behavioral tests: Forced Swimming Test(FST) and Tail Suspension Test(TST).Western Blot and QRT- PCR technique were used to detect myelin-developmental related factors, such as Myelin associated glycoprotein(Mag), Myelin basic protein(Mbp), Myelin-associated oligodendrocyte basic protein( Mobp)、Proteolipid protein(Plp).The ultrastructure of myelin in the prefrontal cortex(PFC) and corpus callosum(CC) was analyzed using transmission electron microscopy(TEM).Results In behavior tests, PRS group showed a significantly higher immobility time and a lower delitescent immobility time than that of NS group(P < 0.05), which confirmed that the PRS group has more desperate time and is more easily to enter to a desperate state. Molecular biological technology results demonstrated a statistically significant decreasing expression of myelin development related factors Mag,Mbp,Mobp,Mog,Sox10,Olig1 and Plp in PRS group(P < 0.05).Myelin morphology observation showed statistically significant thinner myelin sheaths(g-ratio value 0.87±0.074) in PRS mice compared to NS group(g – ratio value 0.72 ±0.072).Conclusion Our data suggest that prenatal stress can induce MDD-like behavior in young and adult offspring. The possible mechanism of this behavioral alteration may be due to down regulation of myelination associated genes, thereby leading to demyelination.