Effects of long-term high fat diet on depressive-like behavior in mice and mechanism of metabolic imbalance of BDNF / 中华行为医学与脑科学杂志

ABSTRACT

Objective:To study the effects of long-term high fat diet on glucose metabolism, depressive-like behavior and the expression of proBDNF/mature BDNF and p75NTR in brain of mice.Methods:Totally 16 8-week-old C57BL/6 mice were randomly divided into two groups with 8 in each group.The mice in STD group were given standard diet (STD) and the mice in HFD group were given high fat diet (HFD). The body weight and food intake were measured every week, and the fasting blood glucose was measured every 4 weeks.After 30 weeks, glucose tolerance test and insulin tolerance test were used to measure islet function, while forced swimming test and tail suspension test were used to detect depression behavior.The brain tissues of mice were collected and the concentrations of proBDNF, mature BDNF and p75NTR were measured by Elisa.The correlation between the above factors and body weight, blood glucose and depression behavior of mice was analyzed.Results:Obesity, hyperglycemia, insulin resistance and depression were observed in HFD group.The concentration of proBDNF in HFD group((4.95±1.12) pg/μg) was significantly higher than that in STD group ((2.19±0.19) pg/μg)) ( t=2.68, P<0.05), the concentration of mature BDNF((1.39±0.18)pg/μg) was significantly lower than that in STD group ((2.26±0.23) pg/μg)) ( t=-2.90, P<0.05), and the concentration of p75NTR ((3.56±1.23)pg/μg)) was significantly higher than that in STD group ((1.42±0.16)pg/μg)) ( t=5.78, P<0.05). Spearman correlation analysis showed that proBDNF and p75NTR were positively correlated with body weight, blood glucose and immobile time, while mature BDNF was negatively correlated with body weight, blood glucose and immobile time. Conclusion:Imbalance of proBDNF and mature BDNF, the upregulation of proBDNF-p75NTR pathway caused by long-term HFD may be the mechanism of the interaction between metabolic abnormality and depression.Regulating the balance of proBDNF and material BDNF signal pathway may play a positive role in the emotional disorders associated with metabolic disorders.