The Concentration Of Nesfatin-1 In Depression Model Rat And Its Role In Pathogenesis Of Depression

Objective:To research the physiological and pathological differences of nesfatin-1 concentration in peripheral blood and central hypothalamus and brainstem in normal rats and depressive rats;To explore the relationship between nesfatin-1 and depressive behavior in rats;To investigate the correlation between nesfatin-1 and hypothalamic-pituitary-adrenal cortical axis and monoamine synthase;Trying to elucidate the possible mechanism of nesfatin-1 in the pathogenesis of depression.Method:Twelve SD rats were randomly divided into nomal control group(NC)and depression model group(CUMS),The open field test(OFT)was used to evaluate the behavior of the two groups before modeling.The preliminary results showed that the two groups had no significant difference in behavior.CUMS group was received 5 consecutive weeks of 7 different chronic unpredictable mild stress(CUMS).NC group was fed normally After 5 weeks,the sucrose preference test(SPT)and forced swimming test(FST)were used to evaluate the behavior of the two groups.The plasma and the fresh hypothalamus and brainstem tissues of the rats were collected,Plasma corticosterone and hypothalamic corticotropin-releasing hormone(CRH)levels were measured in both groups to assess the activity of HPA.The levels of tyrosine hydroxylase and tryptophan hydroxylase in brainstem were compared between the two groups.The levels of nesfatin-1 in plasma,hypothalamus and brainstem were measured too.Plasma index detection method using enzyme-linked immunosorbent assay(Elisa),The central brain tissue index was detected by Western blot.The association between nesfatin-1,HPA axis and monoamine neurotransmitter synthase of depression model rats were analyzed.Results:(1)Behavioral analysis of rats:Behavioral analysis of rats before modeling:The weight[(307.00 ± 11.23)g]in the CUMS group compared that in the NC group[(306.00±13.52)g],and there was no significant difference between the two groups(t =-0.139,P = 0.892),In the OFT,the number of rearing in the CUMS group vs NC group was(7.83±5.71)vs(9.83±3.82),the difference was not statistically significant(t = 0.714,P = 0.492),thehorizontal exercise distance in CUMS group[(10154.00±93.53)cm]compared that in the NC group[(10119.83 ± 75.15)cm],the difference was not statistically significant(t =-0.698,P =0.501).Behavioral analysis of rats after modeling:Compared with NC group,the body weight gain of CUMS group was significantly slower than that of NC group[(85.17 ±28.31)g]vs[(121.00 ± 12.60)g],the difference was statistically significant(t = 2.830,P = 0.018).In SPT,the CUMS group had lower index of sucrose preference[(0.68 ±0.06)%vs(0.91 ± 0.05)%],the difference was statistically significant(t = 2.830,P =0.000).In FST,the CUMS group spent longer time immobile[(108.83 ± 18.90)s versus(65.83 ± 11.16)s,the difference was statistically significant(t =-4.798,P = 0.001).(2)nesfatin-1Compared with the NC group,the plasma nesfatin-1 level in the CUMS group was significantly higher than that in the NC group[(3.50 ± 1.23)ng/ml vs(1.80 ± 0.87)ng/ml],the difference was statistically significant(t =-2.778,p=0.020),and the relative expression of nesfatin-1 protein in the hypothalamus and brainstem was significantly increased,(0.17 ± 0.06)pairs(0.10 ± 0.03)and(0.22 ± 0.12)pairs(0.15 ±0.40),respectively.Differences were statistically significant(t =-2.450,P = 0.037 and t =-4.158,P = 0.002).(3)HPA axisThe level of plasma corticosterone(166.53 ± 5.34pg/ml)in the CUMS group were significantly higher than that in the NC group(132.71 ± 14.31pg/ml),the difference was statistically significant(t =-5.424,P = 0.000).The relative expression level of CRH protein in central hypothalamus was not significantly different from that in NC group(P = 0.537).(4)The relative expression level of TPH and TH protein in brainstemThe expression of TPH protein and TH protein was significantly lower than that of NC group and(P<0.05).The expression of TPH protein was(0.29 ± 0.13)vs(0.52 ±0.05),the difference was statistically significant(t = 4.047,P = 0.002),TH protein expression was(2.69 ± 0.27)pairs(3.27 ± 0.16),the difference was statistically significant(t = 4.584,P = 0.001).(5)Relation analysisThe plasma levels of nesfatin-1 in the CUMS group were positively correlated with the immobile time in forced swimming test(r = 0.922,P = 0.009),and negatively correlated with the body weight gain(r=-0.825,P=0.043)of the rats,and had no correlation with index of sucrose preference(P>0.05).The plasma levels of nesfatin-1 in CUMS group were positively correlated with that of corticosterone(r = 0.827,P =0.042).The brainstem expression level of nesfatin-1 protein in CUMS group was negatively correlated with TPH protein expression(r =-0.832,P = 0.044),but had no correlation with the expression of TH protein(P>0.05).Conclusion:The levels of nesfatin-1 in peripheral blood and central hypothalamus and brainstem were significantly higher in depressive model rats.This pathological change may be involved in the development of depressive-like behavior,possibly through the increase of nesfatin-1,which affects HPA axis-mediated depression-like behavior.Increased expression of nesfatin-1 protein in brainstem may affect the synthesis of 5-HT by affecting the expression level of TPH protein,which may be another important neuroendocrine pathway that affects depression-like behavior.