The Mechanism Study And Effect Of Perinatal Bisphenol A Exposure On Visual Memory Of Rats

Bisphenol A(BPA)was one of the largest industrial chemicals in the word,which mainly used in the production of polycarbonate and epoxy resin.BPA was detected in some fresh foods and processed foods.BPA pollution is mainly derived from food packaging and food processing.BPA was often used in food packaging which can make it colorless,transparent,anti-collision and durable.In China,BPA consumption had accounted for 1/4 of the total consumption in the world.It’s forecast that China will become the largest BPA consumer in 2020.BPA,an classical estrogenic endocrine disrupting chemical(EDC),could disrupt the balance of endocrine system and homeostasis even if a small number of BPA exposure.Many studies have shown that BPA can cross the blood-brain barrier to damage the central nervous system directly,and then affected its learning and memory behavior.In addition,there were many studies have confirmed that BPA is also harmful to the immune system and reproductive system.According to the report,BPA was detected in 90% Americans urine.The main way of human exposed to BPA was diet.Global statistics showed that the exposure of BPA in pregnant women and children was 1.4 and 2 times as compared with adults.And BPA could be detected in breast milk,amniotic fluid,umbilical cord blood and placenta tissue of pregnant women.These suggested that it is commonly that pregnant women and fetuses exposed to BPA.Therefore,many countries have enacted a number of regulations to reduce the potential risk of BPA to protect human health and natural environment.Our study showed that perinatal BPA exposure significantly impaired visual working memory and spatial memory and accompany with anxiety-like behaviors,while the expression of glutamate receptor subunit Glu R2 was significantly decreased in male offspring.And the abnormal behavior was not caused by maternal immune activation and offspring immune activation.In addition,the density of dendritic spine and the maturity of dendritic spine was significantly decreased in primary visual cortex(V1)and prefrontal cortex(PFC),which may affect the information transmission from V1 to PFC.All in all,our findings suggested that perinatal BPA exposure can affect the learning and memory behavior of male offspring,and was accompany with the decreased expression of glutamate receptor subunits and the defect of dendritic spinedevelopment.Methods: The female rats were randomly divided into 2 groups,control group(Ctrl)and BPA exposure group.The dose of BPA exposure was 1 mg/kg/day,and rats exposed to BPA from mating to postnatal 21 days.In the behavioral experiment,the visual memory was detected by object recognition test and grating recognition experiment,and the free exploring behavior and spatial memory were detected by open field test and Y-maze.The morphology of neurons and the density of dendritic spine were observed by Golgi-cox staining.ELISA and q-PCR was used to detect the expression of cytokine.The morphology of glial cells in the brain was detected by immunofluorescence,furthermore Western blotting was used to quantitatively detect the activation of glial cells.Finally,we used Western blotting detect the expression of glutamate receptor which associated with learning and memory.Results:(1)The body weight of female and male rats was normal after perinatal BPA exposure.(2)Behavioral experiment showed that perinatal BPA exposure impaired the visual memory and spatial memory of the male offspring and resulted in anxiety-like behavior,but had no effect on the female offspring.(3)Golgi-cox staining showed that perinatal BPA exposure could decrease the density of dendritic spine in V1 and PFC of male offspring and affect the development and maturation of dendritic spine.(4)ELISA results showed that perinatal BPA exposure did not induce maternal immune activation.(5)Immunofluorescence results showed that perinatal BPA exposure did not result in significant changes in morphology of microglia and astrocytes in V1 and PFC.Furthermore,Western blotting assay was used to detect the expression of GFAP and IBA-1 in V1 and PFC,the results showed that there was no significant change in the expression of GFAP and IBA-1 in PFC and V1.The expression of IL-6 and TGF-β in V1 and PFC were not significantly changed which detected by q-PCR.Therefore,all this results showed that perinatal BPA exposure could not induce inflammation in male offspring,and the activation of glias was not altered after perinatal BPA exposure.(6)Western blotting results showed that the expression of excitatory glutamate receptor subunit Glu R2 in V1 and PFC was significantly decreased after perinatal BPA exposure,but had no effects on the expression of other subunits.Conclusion: The effects of perinatal BPA exposure on learning and memory in male and female offspring was different.Perinatal BPA exposure resulted in impaired visual and spatial memory and also accompany with anxiety-like behavior in male offspring,but had no effects on female offspring.These abnormal behaviors may related to the decreased density of dendritic spine in V1 and PFC and impairment of dendritic spine development induced by BPA exposure in male rats.In addition,the expression of Glu R2 in V1 and PFC was significantly decreased which may also affect the information transmission from V1 to PFC,and then resulted in visual memory impairment in male offspring.In addition,our results indicated that the abnormal behavior had no relation to maternal activation and inflammation in male offspring.