Genetic Susceptibility And Drug Reorientation Study Of Psychiatric Disorders And Neurological Disease

Psychiatric disorders and neurological diseases are a group of diseases characterized by disorders of the nervous system,behavior,and mental activity.Alzheimer's disease is a degenerative central nervous system disease,with hidden cause and complexetiology.And with the development of the aging population,research on the pathogenesis and treatment of Alzheimer's disease has become a focus for scientists.The genetic mechanism of common mental disorders such as schizophrenia,bipolardisorder,and major depressive disorders has been an important part of human genetics.In this study,we studied the effects of new drugs on the pathology and behavior of AD mice model and the association analysis of susceptibility gene for mental disorders.We provide a new direction and choice for the pathogenesis and preventive treatment of complex mental disorders and nervous system disease.As a complex neurodegenerative disease,there is still no effective treatment for Alzheimer's disease.Huge market demand continues to stimulate the research and development of new drugs.In this work,we studied the pathological and behavioral changes of APPswe/PS1dE9 double transgenic mice and the effects of new xanthine oxidase(XO)inhibitors on the pathology and behavior of APPswe/PS1 d E9 double transgenic mice.Our results showed that a large amount of A? plaque deposition occurred in the cerebral cortex and hippocampus of 7 months old transgenic mice.And the 7 months old double transgenic mice has defects in recognition of new objects and learning memory of water maze.New xanthine oxidase(XO)inhibitor febuxostat can significantly improve the new object recognition deficit in APPswe/PS1dE9 double transgenic mice.The LTP level of APPswe/PS1dE9 double transgenic mice was significantly lower,while tne treatment of the combination of febuxostat and Inosine could significantly improve the LTP level of APPswe/PS1dE9 double transgenic mice.The NDST3 gene at 4q26 was a functional candidate gene for mental disorders.Recently,a novel single nucleotide polymorphism rs11098403 in the vicinity ofNDST3 gene was reported to confer risk of schizophrenia in Caucasian.To further investigate whether NDST3 is a risk gene for schizophrenia,bipolardisorder,and major depressive disorders,we genotyped and analyzed eight tag SNPs(rs11098403,rs10857057,rs2389521,rs4833564,rs6837896,rs7689157,rs3817274,rs609512)covering NDST3 gene in 1,248 schizophrenia cases,1,056 majordepression cases,1,344 bipolar disorder cases,and 1,248 controls of Chineseorigin.However,there was no significant difference in allelic or genotypic frequencyobserved between each case group and healthy controls.In addition,a meta-analysis of data from previous studies and this study found no significant association between rs11098403 and schizophrenia,which is consistent with our results of association analysis between NDST3 gene and schizophrenia in Chinese Han population.Accordingly,our study doesnot support that the NDST3 gene plays a major role in schizophrenia,bipolar disorder,and major depressive disorder in the Han Chinese population.