A Research On The Influence Of Prenatal Stress On Offspring Behavior And Its Mechanism

Prenatal stress or inflammation plays an important role in the formation of some mental disorders in the brain.It has recently been postulated that prenatal immune activation,especially when occurring during late gestational stages,may also induce behavioral,anatomical and biochemical changes in offspring(mostly male).It has important significance to understand the mechanism of such chang for the treatment of related mental disorders.In this thesis,we investigated the effects of maternal stress on male offspring behavior during late pregnancy and explored the possible mechanism.We used a model of late pregnancy to mimic the viral immune activation.On the 17 th day of gestation with pregnant Wistar rats,they were treated with the viral mimetic poly I: C(polyriboinosinic polyribocytidilic acid)and treated with saline.On the 21 st day of the male offspring,they were treated with normal saline and different concentrations of pioglitazone(pioglitazone was a microglia activation inhibitor)and tested for offspring on the second day.We tested the cognitive and behavioral paradigms that are known to be sensitive to mental illness,such as sugar preference,autonomic activity,elevated plus maze and water maze.Detection of inflammation is the detection of inflammatory cytokines by RT-PCR.The activation of microglia was determined by immunohistochemistry.Experimental results showed that using the viral mimetic poly I:C treatment in late pregnancy rats can induce offspring nerve inflammation and depression and anxiety symptoms.The Poly I:C induced inflammatory response was determined by the detection of hippocampal IL-1,IL-6,IFN-,CD68,iNOS and TNF-,as well as the activation of microglia in the hippocampus.The offspring of Prenatal Poly I: C-treated mothers showed subtypes,such as lack of pleasure,reduced standing time,and decreased cognitive function,but the offspring treated with pioglitazone did not show these symptoms.Pioglitazone could significantly inhibit the morphological changes of microglia in the hippocampus,decrease the expression of type M1 marker of microglia,and increase the expression of the M2 marker.The results of the experiment show that the maternal Poly I:C challenge in the late pregnancy resulted in significant depressive-like and anxiety-like behaviors in the offspring.The mechanism of offspring behavior abnormality is related to the immune activation of the hippocampus.The maternal challenge in the late pregnancy affects thenormal development of the progeny brain,leading to the immune activation of theoffspring brain,which eventually leads to abnormal behavior of offspring.The use of drugs to inhibit the immune activation of the offspring of the brain can improve the pathological behavior of the offspring,indicating that inhibition or reversal of the immune activation of the brain is an effective method for the treatment of brain related mental disorders.It is of positive value to the occurrence and treatment of mental disorders in the offspring of the infected mothers.