Association Study Of Aging Characteristics Of Panic Disorder With TERT Gene And Resting-state Brain Function

Background: PD(panic disorder)is commonly co-morbid with age-related diseases including depression and Alzheimer's disease and is at risk for accelerated aging.An emerging view suggests that PD and other aging-related diseases may have a common pathophysiological basis.The memory decline and social function impairment of PD patients are considered to be one of the characteristics of aging.TERT(telomerase reverse transcriptase)gene is believed to play an important role in the accelerated aging and neurodegeneration of cells.TERT gene expression is closely related to anxiety-like behaviors.This suggests that the TERT gene may be related to the pathophysiological mechanism of PD aging characteristics and act by altering brain function.In this study,the TERT gene is associated with aging and PD as the starting point,and the relationship between TERT gene expression and DNA methylation and PD aging characteristics(memory,social function)was jointly explored from both human and animal experiments.Methods:Chapter 1 Association between TERT gene and fear memory in PDEnrolled 15 adult male mice withTERT gene knockout and 21 adult male mice with complete TERT gene as the control group,put them in the designed fear box,and make a contextual recent fear memory model,24 hours later Observe the changes of the acquired value of fear memory in the two groups of mice.Chapter 2 Association between methylation of hTERT gene promoter and PD aging in memory and social functionPromoter methylation within the gene encoding for TERT was measured in PD(n=32),and eligible healthy controls(HCs,n=22).Cp G regions and sites for analysis were used to the relationship with clinical characteristics,HAMA(Hamilton anxiety scale),PDSS(panic disorder severity)scale,Webster memory test and Re Ho(regional homogeneity).Results:Chapter 1 Association between TERT gene and fear memory in PDAfter TERT knockout mice were modeled with contextual recent fear memory,their fear learning ability was lower than that of normal mice(t=2.471,p=0.0269)Chapter 2 Association between methylation of hTERT gene promoter and PD aging in memory and social function(1)The average methylation level of the hTERT gene promoter region and Cp G7 site in the PD patient group were significantly lower than those in the normal control group(mean: t=-2.869 p=0.0071;Cp G7: t=-2.562 t =2.562 p=0.0133).There are 13 differential Cp G sites on the Cp G7 island of hTERT gene(cg1:p=0.030;cg2:p=0.041;cg3:p=0.012;cg4:p=0.031;cg5:p=0.017;cg6:p=0.012;cg7:p=0.0088;cg8:p=0.0081;cg9:p=0.0366;cg10:p=0.0176;cg11:p=0.0014;cg12:p=0.016;cg13:p=0.037).(2)Compared with the HCs,the PD patients had significantly lower scores in comprehension(p=0.003).Through Pearson correlation analysis,it was found that the methylation level of cg13 site was positively correlated with the HAMA5 item scores in the HAMA scale for evaluating memory and attention(r=0.357,p=0.045).(3)The results of Pearson correlation analysis showed that(n=17 persons),the total score of the PDSS scale was related to the cg2(r=-0.515,p=0.030)and cg13sites(r=-0.483,p=0.049)located on the Cp G7 fragment.The degree of methylation is negatively correlated,and the SFI(social functional impairment)score in the PDSS scale is correlated with cg2(r=-0.557,p=0.020)and cg13(r=-0.562,p=0.019).The degree of methylation is negatively correlated.(4)The reduction of Re Ho values in the left central posterior gyrus and inferior parietal lobules of PD patients is negatively correlated with the SFI score of PD patients,and overlaps with cg2 locus methylation-related brain regions(r =-0.736,p=0.001).After controlling for age and sex,the linear regression models revealed an interaction between hypomethylation of cg2 and Re Ho modulated by the Cp G site in the left PCG(p=0.043).In PD,the hypomethylation of the Cp G site decreased social function by moderating the function of left PCG(a=-8.478,p<0.005;c=132.715,p<0.005).Conclusion: TERT gene expression is closely related to changes in PD aging characteristics in memory and social functions.The promoter region of hTERT gene in PD patients is generally hypomethylated,and it is related to the severity of the clinical symptoms of PD,the decline of memory and the degree of impairment of social function.The study supported that hTERT methylation modulates the local brain function of the postcentral gyrus to affect the social function of PD patients.It is indicates that the changes in hTERT gene methylation may affect the changes related to PD aging characteristics,and may become a biological marker for evaluating PD aging characteristics.The study provides a basis for the TERT gene to affect the changes in PD aging characteristics,and provides a multi-dimensional basis for the potential genetic pathology of PD.