Imbalance of leptin pathway and hypothalamus synaptic plasticity markers are associated with stress-induced depression in rats

Abstract

Increasing evidences have indicated that chronic stress is a contributing risk factor in the development of psychiatric illnesses including depression. The mechanisms of their psychopathology are multifaceted and include, besides others, alterations in neuroendocrine function and brain plasticity. In the present study, we investigated the behavior of stressed animals by the sucrose preference test, open field test (OFT), forced swimming test (FST), and tail-suspension test (TST). The response of hypothalamic–pituitary–adrenal (HPA) axis, leptin pathway, and synaptic plasticity markers in the hypothalamus were also detected. Our data demonstrated that chronic unpredictable mild stress (CUMS) could induce depression-like behavior in rat model, accompanied with the hyperactivity of HPA axis. The serum leptin level and hypothalamic mRNA expression of leptin receptor (LEPR) were both decreased. Results of Pearson test showed that the decreased serum leptin level was negatively related with the locomotion and rearing frequency in the open-field test, and the hypothalamic mRNA expression of LEPR was inversely related to serum CORT concentration. Moreover, our results showed that the mRNA expression of synaptotagmin I and synapsin I was both increased in the hypothalamus of CUMS rats, providing new evidence for the synaptic plasticity change in the hypothalamus of depressive rats. Furthermore, our results demonstrated that the mRNA expression of synaptotagmin I, but not synapsin I, was correlated with the depression-like behaviors and HPA axis hyperactivity in CUMS rats. Together with our previous results, the current findings suggested that a CUMS rat model could be effectively used to study molecular mechanisms underling the depressive symptomatology.