2-Phenylethylamine (PEA) Ameliorates Corticosterone-Induced Depression-Like Phenotype via the BDNF/TrkB/CREB Signaling Pathway.

Young-Ju Lee,Hye Ryeong Kim,Byoung-Seok Lee,Sung-Ae Hyun,Moon Yi Ko,Chang Youn Lee,Dae Youn Hwang,Minhan Ka

doi:10.3390/ijms21239103

Abstract

Depression is a serious medical illness that is one of the most prevalent psychiatric disorders. Corticosterone (CORT) increases depression-like behavior, with some effects on anxiety-like behavior. 2-Phenethylamine (PEA) is a monoamine alkaloid that acts as a central nervous system stimulant in humans. Here, we show that PEA exerts antidepressant effects by modulating the Brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element binding protein (CREB) signaling pathway in CORT-induced depression. To investigate the potential effects of PEA on CORT-induced depression, we first treated CORT (50 μM)-induced hippocampal neurons with 100 μM PEA for 24 h. We found that treatment with CORT altered dendritic spine architecture; however, treatment with PEA rescued dendritic spine formation via regulation of BDNF/TrkB/CREB signaling. Next, we used a mouse model of CORT-induced depression. Mice were treated with CORT (20 mg/kg) for 21 days, followed by assessments of a battery of depression-like behaviors. During the final four days of CORT exposure, the mice were treated with PEA (50 mg/kg). We found that CORT injection promoted depression-like behavior and significantly decreased BDNF and TrkB expression in the hippocampus. However, treatment with PEA significantly ameliorated the behavioral and biochemical changes induced by CORT. Our findings reveal that PEA exerts antidepressant effects by modulating the BDNF/TrkB/CREB signaling pathway in a mouse model of CORT-induced depression.

Highlights

Major depressive disorder (MDD) is a highly prevalent neuropsychiatric disorder and is a major public health concern [1]
We found that the levels of SYP and PSD95 decreased by 23% and 42%, respectively, in CORT-induced hippocampal neurons (Figure 2A–C)
We found that the levels of Brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) decreased by 24% and 34%, respectively, in CORT-induced hippocampal neurons compared with control neurons (Figure 2D–F)

Summary

Introduction

Major depressive disorder (MDD) is a highly prevalent neuropsychiatric disorder and is a major public health concern [1]. Chronic exposure of rodents to corticosterone (CORT) is widely used to induce depression-like behavior and neurochemical changes associated with MDD symptoms, including anhedonic and anxiety behaviors [11,12] and decreased levels of synaptic-related proteins [13,14]. A chronic CORT-induced rodent model is appropriate for evaluating the efficacy of antidepressant drugs and exploring the mechanism of action of antidepressants [15]. AMPK activation produces anti-depressant effects, which are mediated hippocampal neurogenesis via PKCζ/NF-κB/BDNF/TrkB/CREB signaling in neurons [19]. Chronic antidepressant treatments activates BDNF mRNA and protein expression in distinct regions of the brain [31], and pretreatment with antidepressants prevents stress-induced decreases in hippocampal BDNF expression [32]. The TrkB receptor has been shown to be related to antidepressant treatment [33]

Methods

Results

Discussion

Conclusion