The Mechanism Study And Effect Of Juvenile Bisphenol A Exposure On The Spatial Memory Of Rats

As an environmental endocrine disruptors,BPA are widely used in the production of polycarbonate and epoxy resin,such as canned coatings,food packaging materials,beverage containers,baby bottles and dental closed agent,and so on.Under the condition of wear and aging,high temperature,strong acid and alkali,the BPA ester bond of these products will be hydrolyzed,thus releasing the BPA monomer.With the widespread use and degradation of these items,the emission of BPA into environment icreased dramatically.For human,it has become an inevitable environmental pollutants.The Centers for Disease Control of USA reported that the BPA in 95 percent of urine samples were tested from 394 people.Bisphenol A(BPA)could cause human and animal reproductive system,nervous system,immune system,endocrine system abnormalities,at present,the international research on bisphenol A has become a hot issue.The studies of BPA exposure have always focused on prenatal and adolescence phases in the previous studies.Juvenile is also a critical phases for the development of the central nervous system.However,effects of BPA exposure on the brain function during juvenile and underlying mechanism remain elusive.In our study,we found showed there was a markedly decreased spatial memory deficit of male rats in a dose-dependent manner after juvenile BPA exposure,accompanied with the decreased expression of glutamate receptor subtypes,NR2 and GluR1.Moreover,such impairments of hippocampus were not due to the altered activity of hypothalamus,which participating in the regulation of estrogen release in brain.Importantly,there was an obvious decreased glutamate receptors expression in the primary visual cortex of male rats,which could perturb the information input to the hippocampus.Additionally,there was a significant decline of spine density,to which extent attributable to the decrease of presynaptic projection from sensory cortices.Thus,our study shed light on the gender-specific mechanism of BPA-induced memory deficits.Methods:A large number of male and female SD rats were divided into four groups,a c ontrol group and three BPA-exposed groups(BPA 1: 0.04mg/kg/d,BPA 2: 0.4mg/kg/d,BPA 3:4mg/kg/d).The BPA-exposed group acquired BPA via intraperitoneal injection from postnatal 21 days to postnatal 49 days.Morris-water maze and Open field test was assessed for whether the BPA exposure can impair the spatial memory and anxiety like behavior of rats;Golgi-Cox staining was used to assess the morphologic structure about learning and memory;The expression of excitatory glutamate receptor and estrogen receptor in the hippocampus,primary visual cortex(V1)and hypothalamus was detecte d by Western blotting to discuss its possible molecular mechanism.Results of the study: 1.The juvenile BPA exposure can not impaired their body weight,drinking water,food intake and physiological status of male and female rats(p > 0.05).2.The juvenile BPA exposure impaired spatial memory in male rats,accompanied by an xiety like behavior(P > 0.05),but had no effect on female rats.3.The density of dendritic spine of pyramidal neurons in hippocampus was decreased after juvenile BPA exposure(p < 0.05).4.Western blotting results showed that the expression of excitatory glutamate receptor,NR2 and GluR1,in hippocampus was significantly down-regulated after juvenile BPA exposure;and the expression of NR2 in primary visual cortex(V1)was significantly do wn-regulated after juvenile BPA exposure;and the expression of excitatory glutamate receptor in hypothalamus showed no significant change after juvenile BPA exposure.The expression of estrogen receptor in hippocampus and primary visual cortex(V1)did not change,but the expression of estrogen receptor beta in hypothalamus was decreased after juvenile BPA exposure.Conclusion: The juvenile BPA exposure impaired the spatial memory in a dose-depende nt manner and with sex-specificity.The juvenile BPA exposure resulted in spatial mem ory impairment in male rats which accompanied by anxiety like behavior,but not found in female rats.At the same time,the density of dendritic spines in hippocampal pyrami--dal neurons was decreased in BPA-exposed male rats,and the excitatory glutamate rec-eptors and estrogen receptors may be involved in this process.