The Mechanism Study And Effect Of Early Development Bisphenol A Exposure On Working Memory Of Rodents

Bisphenol A is one of the largest industrial chemicals in the world,which is mainly used to produce polycarbonate and epoxy resin.At present,bisphenol A has been found in water,air,soil and other environmental media,and bisphenol a mainly enters human body through ingestion.As an endocrine disruptor,bisphenol A has the properties of estrogen,which can cause physiological dysfunction of organism,such as endocrine disorders.Bisphenol A has been found to cross the blood-brain barrier,than can directly damages the central nervous system,including the learning and memory ability of rodents.Whether bisphenol A exposure on the different development phases exerts similar effects on the prefrontal cortex dependent visual memory is still elusive.First of all,we constructed the model of mice exposed to bisphenol A during pregnancy and lactation,and detected the damage of their working memory.The results showed that compared with the control group,the mice exposed to bisphenol A showed significant damage of working memory in the task of new object recognition and T maze.Prefrontal cortex is mainly responsible for memory storage,and primary visual cortex is the key to link visual activity and working memory.In vivo,our electrophysiological results showed that the amplitude of gamma oscillation in the primary visual cortex decreased significantly,and the expression of GABAA ? 1subunit in the primary visual cortex decreased significantly,indicating that the information transmission from the primary visual cortex to the prefrontal cortex may be damaged.Than we detected the expression of glutamate receptor in prefrontal cortex.The results showed that the expression of Glu R2,a glutamate receptor subunit closely related to learning,decreased significantly.It is suggested that bisphenol A exposure during pregnancy and lactation can damage the working memory ability of mice by affecting the information transmission upstream of prefrontal cortex and reducing the expression of Glu R2,the excitatory receptor subunit in this brain area.In the second part of the study,we constructed two important developmental stages:pregnancy and lactation,juvenile and adolescent bisphenol A exposure rat models to detect the working memory impairment at the end of exposure and in the recovery period.Results compared with the control group,bisphenol A exposed rats showed significant visual working memory impairment in the task of new object recognition.In addition,we found that the damage of learning and memory can be recovered.After 20 days of bisphenol A exposure in juvenile and adolescent,the rats showed normal working memory ability in the task of new object recognition,along with the recovery of spike density of pyramidal neurons in prefrontal cortex and the recovery of Glu R2 expression.However,the rats exposed to bisphenol A during pregnancy and lactation still showed significant working memory impairment in the task of new object recognition compared with the control group after 20 days of recovery period,and the density of pyramidal neurons in the prefrontal cortex decreased and the expression of Glu R2 decreased.The damage caused by bisphenol A exposure was only recovered after a further 20 day recovery period was given.In conclusion,our study shows that bisphenol A exposure during pregnancy and lactation can significantly damage the working memory of mice,and the function of primary visual cortex and prefrontal cortex is damaged.Bisphenol A exposure in pregnancy,lactation,adolescence and early childhood can damage the working memory of rats,and the effect of bisphenol A exposure in pregnancy and lactation on visual working memory of rats is more profound than that in adolescence and early childhood.Our work provides an important theoretical basis for the influence of bisphenol A exposure on human beings,and provides a possible test standard for clinical diagnosis.