Caffeic Acid Phenethyl Ester Ameliorates Depression- and Anxiety-like Behaviors of Mice Exposed to Chronic Mild Stress

Atsushi Toratani

doi:10.17303/jnnd.2014.202

Abstract

Depression and anxiety like symptoms appeared in mice when they were kept in cages and sequentially subjected to leaning, drenching, and rotation within 1-2 days for 3 weeks (chronic mild stress: CMS). The depression-like symptom was evaluated by performing the tail suspension test; and the anxiety-like symptom, by the elevated plus-maze test and light-dark box test. Caffeic Acid Phenethyl Ester (CAPE), a component of propolis, showed a preventive effect against both depression- and anxiety-like symptoms when administered during the stress loading, and CAPE also displayed a therapeutic effect against both symptoms when administered after the stress loading. Furthermore, CAPE restored the CMS-induced decrease in the level of the phosphorylated forms of extracellular signal-regulated protein kinases (ERK) 1/2 and cAMP-response element binding protein (CREB) in the hippocampus to a normal level. These results suggest that CAPE is a promising tool for therapy of mood disorders through activation of the hippocampal ERK1/2-CREB signaling cascade.

Highlights

Depression and anxiety frequently coexist [1,2] and are sometimes preceded by stressful life events [3, 4]
Caffeic Acid Phenethyl Ester (CAPE), a component of propolis, showed a preventive effect against both depression- and anxiety-like symptoms when administered during the stress loading, and CAPE displayed a therapeutic effect against both symptoms when administered after the stress loading
Brain-Derived Neurotrophic Factor (BDNF) plays roles in the maintenance of neuronal function and plasticity during development and adulthood [7,8]. This factor is highly expressed in the hippocampus, and a growing body of evidence indicates that hippocampal BDNF is involved in the etiology and treatment of stress-related mood disorders including depression and anxiety [6,9]

Summary

Introduction

Depression and anxiety frequently coexist [1,2] and are sometimes preceded by stressful life events [3, 4]. BDNF plays roles in the maintenance of neuronal function and plasticity during development and adulthood [7,8] This factor is highly expressed in the hippocampus, and a growing body of evidence indicates that hippocampal BDNF is involved in the etiology and treatment of stress-related mood disorders including depression and anxiety [6,9]. We recently found that CAPE increased the level of phosphorylated forms of ERK1/2 and cAMP-response element-binding protein (CREB) in cultured central neurons (Soga et al, unpublished results), suggesting BDNF-like biological activity of CAPE From these observations, CAPE would be expected to have ameliorative activity toward stress-related mood disorders including depression and anxiety, as in the case of BDNF. We examined the effects of CAPE on depressionlike and anxiety-like symptoms and the influence of CAPE on the signal transduction pathways of BDNF by using a CMS animal model

Methods

Results

Conclusion