Acupuncture Activates ERK-CREB Pathway in Rats Exposed to Chronic Unpredictable Mild Stress

Jun Lu,Li Hu,Jian-You Guo,Ya Tu,Jia Liang,Jun-Ren Wang

doi:10.1155/2013/469765

Abstract

Extracellular signal-regulated kinase (ERK)-cAMP response element binding protein (CREB) signal pathway has been implicated in the pathogenesis of depression. There is growing evidence that acupuncture in traditional Chinese medicine has antidepressant-like effect. However, the effect of acupuncture on ERK-CREB pathway remains unknown. In our study, the antidepressant-like effect of acupuncture treatment was measured by sucrose intake test and open field test in rats exposed to chronic unpredictable mild stress (CUMS) for 4 weeks. The protein levels of ERK1/2, CREB, phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated CREB (p-CREB) in the hippocampus (HP) and prefrontal cortex (PFC) were examined by Western blot analysis. Our results showed that CUMS rats exhibited the reduction in behavioral activities, whereas acupuncture stimulation at acupoints Baihui (Du20) and Neiguan (PC6) reversed the behavioral deficit. In addition, exposure to CUMS resulted in the decrease of p-ERK1/2 and p-CREB in the HP and PFC. Acupuncture increased the ratio of p-ERK1/2 to ERK1/2 and the ratio of p-CREB to CREB in the HP and PFC. Our study suggested that one potential way, by which acupuncture had antidepressant-like effect, might be mediated by activating the ERK-CREB pathway in the brain.

Highlights

Depression is the leading cause of disability and the 4th leading contributor to the global burden of disease in the world, with a lifetime prevalence of up to 17% [1]
We investigated the effects of acupuncture on the behavioral activities and detected protein levels of ERK1/2, cAMP response element binding protein (CREB), p-ERK1/2, and pCREB in the hippocampus (HP) and prefrontal cortex (PFC) by using Western blot analysis
The major finding of the present study is that chronic stress exposure caused deficits in extracellular signal-regulated kinase (ERK) and CREB activation in the HP and PFC, which could be reversed by acupuncture treatment

Summary

Introduction

Depression is the leading cause of disability and the 4th leading contributor to the global burden of disease in the world, with a lifetime prevalence of up to 17% [1]. Attempts have been made to seek alternative medicine for treatment options [3]. In Chinese medicine, acupuncture has been widely used to treat depression [4, 5]. The mechanism underlying the acupuncture treatment in depression remains unclear. The extracellular signal-regulated kinase (ERK)-cAMP response element binding protein (CREB) signal pathway is implicated in learning, memory, and neuroplasticity [6] and plays an important role in regulating many brain functions, including cell growth, differentiation, apoptosis, and cellular responses to stress [7]. It has been reported that ERK-CREB signal pathway involves in stress response and depression [8]. Little is known about whether acupuncture could affect ERK-CREB signal pathway in stress and depression

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Methods

Conclusion