Relationship Between The Memory Behavior Of Nuprl Gene Knockout Mice C57 And The P-tau Protein In Hippocampus By METH Exposure

BackgroundMethamphetamine(methamphetamine,METH)is a type of neurostimulant that is widely abused.Because of its strong excitability for the central nervous system,relatively simple processing,and low price,it has become the second largest drug of abuse worldwide after cannabis.METH will not only have a huge negative impact on society,but also seriously endanger health.A large number of clinical studies and animal experiments have confirmed that METH can cause cognitive impairment,the main performance includes the decline of learning and memory function.METH is neurotoxic and changes in cognitive memory similar to Alzheimer's disease(AD).In the early stage of the laboratory,it was found that,compared with normal mice,the expression of Nuprl protein was suppressed,and the excitability of mice after exposure was reduced.This suggests that inhibiting the expression of Nupr1 protein may reduce the degree of cognitive memory impairment caused by METH.So,how exactly does METH cause cognitive memory dysfunction?What role does Nupr1 protein play after being infected with METH?Can inhibiting the expression of Nupr1 protein improve the adverse effects after exposure?It is a question discussed in this research.This research mainly explores the effect of METH on memory behavior through behavioral experiments and molecular biology techniques,and explores the relationship between the change in expression of p-Tau in knockout Nuprl gene mice and the change in memory behavior.Find possible intervention or treatment targets and theoretical basis.MethodsWe constructed METH models of different doses of poisoning,used knockout Nuprl gene mice,observed the performance of mice in the shuttle box experiment after poisoning,evaluated the cognitive memory behavior of mice,and then used Western Blot,immunofluorescence and Immunohistochemical technique was used to detect the changes in the expression of p-Tau protein in the hippocampal brain region,and to analyze the relationship between the behavioral changes and p-Tau protein changes after administration of two types of mice(knock-out and knock-out genes)Mechanisms affecting cognitive memory.Results1.After 24 hours of exposure to METH,the exercise ability of the mice was not significantly affected.There was no significant difference in the level of stress and anxiety in mice.Prove that METH will not affect the mental state of mice in a short time.2.Wild-type mice:After being exposed to METH at 5mg/kg and 10mg/kg,the active avoidance rate decreases,the non-response rate increases,and the cognitive memory function is seriously impaired.After 1mg/kgMETH,the active avoidance rate and non-response rate were no different from the control group,and the cognitive memory effect was not obvious.3.N uprl protein-knockout mice:After being treated with 5 mg/kg of METH,the active avoidance rate and non-response rate were not significantly different from the control,indicating that the functions related to cognitive memory were less affected.After 1 mg/kg of METH,the active avoidance rate and non-response rate were not different from the control group,indicating that the effects related to cognitive memory were not obvious.After 10mg/kg of METH,the active avoidance rate decreased and the non-response rate increased,indicating that the functions related to cognitive memory may be severely impaired.4.By WB,immunofluorescence and immunohistochemical staining of mouse hippocampal protein,we found that after METH exposure,the hippocampus expressed a large amount of p-Tau protein.After inhibiting the expression of Nuprl protein in vivo,the expression of p-Tau protein in the mouse brain did not increase significantly at 5 mg/kg.ConclusionWe believe that METH(5mg/kg)can induce increased expression of p-Tau protein in the hippocampal brain region of wild-type c57 mice,and knocking out Nuprl protein can inhibit the production of p-tau protein to a certain extent,and finally Academically,it is the improvement of learning and memory impairment in mice.Low dose of METH will not cause cognitive memory dysfunction in mice.Cognitive memory impairment caused by high-dose METH cannot be improved by knocking out Nuprl protein.Therefore,the molecular pathways related to Nuprl protein may become one of the research directions in the study of the mechanism of neurotoxicity and cognitive memory impairment in middle and high dose METH.