Effects Of 7,8-Styrene Oxide On Learning And Memory Ability And PKA-ERK-CREB Signal Pathway In Rats

ObjectivesThe purpose of this study is to investigate the effects of 7,8-styrene oxide(SO)on learning and memory impairment in the hippocampus and its mechanism by conducting neurobehavioral tests on rats exposed to 7,8-styrene oxide,detecting the content of lipid peroxidation and antioxidant indicators,neurotransmitter content,and the expression level of related genes and proteins such as PKA-ERK-CREB signaling pathway in the hippocampus of rats.To provide theoretical basis for preventing neurotoxic damage caused by 7,8-styrene oxide in humans.MethodsSelect 40 healthy adult SPF grade SD rats(Sprague Dawley),with half male and half female,weighing approximately(200 ± 20 g).Divide the rats into 4 groups based on their weight,with 10 rats in each group.The control group,low dose of SO 166.6mg/kg(1/12LD50),medium dose of SO 333.3 mg/kg(1/6LD50),and high dose of SO666.6 mg/kg(1/3LD50)were administered on an empty stomach once a day for 4weeks.Weigh the rats every week and observe the changes in their weight.After the completion of poisoning,Morris water maze experiment was used to evaluate their spatial memory and exploratory ability.The level of oxidative stress in the hippocampus of rats was observed by detecting the antioxidant index and lipid peroxidation: the content of glutathione(GSH),malonaldehyde(MDA)and the activity of superoxide dismutase(SOD).The changes of neurotransmitters in rats were observed by detecting the contents of dopamine(DA),5-hydroxytryptamine(5-HT),glutamate(Glu)and the activity of monoamine oxidase(MAO).The expression levels of PKA-ERK-CREB signaling pathway related genes and proteins in the rat hippocampus were detected using Real time PCR and Western blot methods.Results1.Changes in the body weight of rats: The weight changes of rats in each group were detected,and it was found that the weight of rats in each group increased.The high-dose SO group had the least weight gain compared to the control group(P<0.05).2.Morris Water Maze results: The results of positioning navigation experiment showed that the latency time of searching platform was significantly longer in SO high-dose group than in control group(P<0.05).In the first space exploration experiment,the time to enter the platform of rats in SO high-dose group was also significantly extended(P<0.05).The retention time of rats in SO medium dose and high dose groups was shortened(P<0.05).3.Neurotransmitter results:Compared with the control group,the DA content in the hippocampus tissue of rats in the high-dose SO group significantly decreased(P<0.05);The 5-HT content of rats in the SO medium and high dose groups significantly decreased(P<0.05);The MAO activity of rats in the high-dose SO group significantly increased(P<0.05);The Glu content in the hippocampus of rats in the medium dose group significantly increased,with significant differences(P<0.05).4.Results of oxidative stress related indexes:Compared with the control group,the activity of SOD and the content of GSH in the hippocampus of rats in the high-dose SO group significantly decreased(P<0.05),while the content of MDA significantly increased(P<0.05).5.Real-time PCR experiment results: Compared with the control group,the expression of PKA,ERK1,ERK2,BDNF,and CREB m RNA in the hippocampus of rats in the medium and high SO dose groups was significantly reduced(P<0.01).6.Western blot results: Compared with the control group,there was no significant change in the protein expression of ERK1,ERK2,and CREB in the hippocampus of rats with different doses of SO;However,the relative expression levels of PKA,p-PKA,p-ERK1,p-ERK2,p-CREB,and BDNF proteins decreased in the high-dose group(P<0.05).Conclusion1.Exposure to 7,8-styrene oxide can lead to impairment of learning and memory ability in rats.2.Exposure to 7,8-styrene oxide can lead to an increase in MAO activity and Glu content,a decrease in 5-HT and DA content,and a decrease in gene and protein expression of PKA,ERK1,ERK2,CREB,and BDNF in the hippocampus of rats.It is speculated that the possible mechanism is through changes in neurotransmitters,which in turn affect the PKA-ERK-CREB signaling pathway and ultimately affect the learning and memory abilities of rats.3.Exposure to 7,8-styrene oxide leads to a decrease in SOD and GSH content and an increase in MDA content in the hippocampus of rats,leading to lipid peroxidation in the hippocampus.This may lead to damage to the learning and memory abilities of rats through changes in the PKA-ERK-CREB signaling pathway.