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

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.

Escitalopram Targets Oxidative Stress, Caspase-3, BDNF and MeCP2 in the Hippocampus and Frontal Cortex of a Rat Model of Depression Induced by Chronic Unpredictable Mild Stress

“…External stressors determine the activation of the hypothalamic-pituitary-adrenal (HPA) axis. Particularly, if stress becomes chronic, it determines the dysregulation of the HPA axis and consequently an abnormal and sustained increase of glucocorticoids levels, which leads to oxidative stress [ 11 , 12 , 13 , 14 ]. In addition, chronic stress is a source of ROS through the activation of brain microglia or NF-kB pathway that in turn will produce pro-inflammatory cytokines [ 15 ].…”

“…Chronic mild stressed mice showed increased caspase-3 and Bax positive cells in the hippocampus as compared to control [ 18 ]. These effects decreased neurogenesis and produced neuronal cell damage and apoptosis along with the occurrence of depressive behaviour ultimately proving the pro-apoptotic and anti-neurogenic effect of chronic stress [ 13 , 14 , 19 ].…”

The Associations between COMT and MAO-B Genetic Variants with Negative Symptoms in Patients with Schizophrenia

“…Phenylethylamine was previously shown to promote energy and elevate mood while its main metabolite phenylacetic acid was decreased in biological fluids of schizophrenic patients [93]. More recently, phenylethylamine treatment restored anhedonia in mice [94]. Moreover, the inhibition of MAO-B is already a treatment target for Parkinson's disease and major depression; those drugs have also been evaluated for their potential in the treatment of Alzheimer's disease, Lewy Body diseases with dementia, amyotrophic lateral sclerosis, and Huntington's disease [37].…”

Tao-Hong-Si-Wu Decoction improves depressive symptoms in model rats via restorations of neural transmitters and ameliorations of BDNF-CREB-arginase I axis disorders

“…Evidence support that BDNF as well as its membranal receptor in the brain, TrkB, in the hippocampus is implicated in both the pathogenesis of depression and antidepressant actions [39]. Several studies have shown that medications targeting the BDNF-TrkB-CREB axis improve depression-like symptoms in animal models [40]. Interestingly, a putative compound hydroxysa or A issued from sa ower is reported to up-regulate BDNF expression [41].…”