Apelin-13 Upregulates BDNF Against Chronic Stress-induced Depression-like Phenotypes by Ameliorating HPA Axis and Hippocampal Glucocorticoid Receptor Dysfunctions. (15th October 2018)

• Record Type: Journal Article
• Authors: Dai, Ting-Ting; Wang, Bo; Xiao, Zhi-Yong; You, Yong; Tian, Shao-Wen
• Is Part Of: Neuroscience. Volume 390(2018)
• Page Start: 151
• Page End: 159
• Publication Date: 2018-10-15
• Subjects: ANOVA analysis of variance -- BDNF brain-derived neurotrophic factor -- CWIRS chronic water-immersion restraint stress -- DST dexamethasone suppression test -- FST forced swimming test -- GR glucocorticoid receptor -- HPA hypothalamic–pituitary–adrenal -- i.c.v intracerebroventricular -- LAT locomotor activity test -- SPT sucrose preference test -- TST tail suspension test; apelin -- chronic stress -- depression -- HPA axis -- glucocorticoid receptor -- BDNF; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.08.018
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Chronic water-immersion restraint stress (CWIRS) exposure upregulated apelin and APJ levels in the rat hippocampus. Apelin-13 ameliorated CWIRS-induced depression-like phenotypes and HPA axis hyperactivity. Apelin-13 ameliorated CWIRS-induced hippocampal glucocorticoid receptor nucleus translocation hypoactivity. TrkB-dependent BDNF signaling was required for apelin-13-mediated effects. Abstract: Localization of apelin and its receptor APJ in limbic structures such as the hippocampus suggests potential involvement of apelin/APJ signaling in stress-related emotional responses. We have recently reported that apelin-13 exerts antidepressant-like actions in acute stressed rats, and that the hippocampus is a critical brain region mediating its actions. However, the neural mechanism underling antidepressant-like actions of apelin-13 is still largely unknown. The aim of the present study is to determine whether apelin-13 ameliorates chronic water-immersion restraint stress (CWIRS)-induced depression-like phenotypes and its neural mechanism in rats. Here, we report that CWIRS exposure leaded to upregulation of apelin/APJ signaling in the hippocampus. Apelin-13 ameliorated CWIRS-induced depression-like phenotypes including hedonic-like deficit and behavioral despairs. Moreover, apelin-13 ameliorated hypothalamic–pituitary–adrenal (HPA) axis hyperactivity, and hippocampal BDNF expression deficit and glucocorticoid receptor (GR) nucleus translocation hypoactivity in chronic stressed rats. Finally, apelin-13-mediated effects were blocked by the selective TrkB receptor antagonist ANA-12. These results suggest that apelin-13 upregulates BDNF against chronic stress-induced depression-like phenotypes by ameliorating HPA axis and hippocampal GR dysfunctions.