Abstract
BackgroundThe extracellular signal-regulated kinase (ERK) signaling pathway is considered to be associated with the pathogenesis and treatment of depression. Acupuncture has been demonstrated to ameliorate depression-related behavior and promote neurogenesis. In this study, we explored the role of the ERK signaling pathway in the antidepressant-like effects of acupuncture in rats exposed to chronic unpredictable mild stress (CUMS).MethodsEighty male Sprague–Dawley rats were randomly divided into eight groups: control group, model group, model + Acupuncture group (Acu group), model + fluoxetine group (FLX group), model + DMSO group (DMSO group), model + PD98059 group (PD group), model + Acupuncture + PD98059 group (Acu + PD group) and model + fluoxetine + PD98059 group (FLX + PD group). Except for the control group, all rats were subjected to 3 weeks of CUMS protocols to induce depression. Acupuncture was carried out for 10 min at acupoints of Baihui (GV-20) and Yintang (GV-29) each day during the experimental procedure. The ERK signaling pathway was inhibited using PD98059 through intracerebroventricular injection. The depression-like behaviors were evaluated using the sucrose intake and open-field tests. The protein levels of ERK1/2, phosphor (p)-ERK1/2, cAMP response element-binding protein (CREB), p-CREB and brain-derived neurotrophic factor (BDNF) in the hippocampus were examined using western blot.ResultsAcupuncture ameliorated the depression-like behaviors and dysfunction of the ERK signaling pathway in the hippocampus of CUMS rats. PD98059 pretreatment inhibited the improvements brought about by acupuncture on the ERK signaling pathway.ConclusionsTaken together, our results indicated that acupuncture had a significant antidepressant-like effect on CUMS-induced depression model rats, and the ERK signaling pathway was implicated in this effect.
Highlights
The extracellular signal-regulated kinase (ERK) signaling pathway is considered to be associated with the pathogenesis and treatment of depression
We used PD98059 pretreatment to inhibit the activity of p-ERK1/ 2; we evaluated the behavioral activities by the sucrose intake and open field tests, as well as the protein levels of ERK1/2, p-ERK1/2, cAMP response element-binding protein (CREB), p-CREB and Brain-derived neurotrophic factor (BDNF) in the hippocampus by western blot analysis
Interesting, our finding showed that p-ERK1/2, CREB and p-CREB, but not ERK1/2, proteins reduced in the hippocampus of rats exposed to chronic unpredictable mild stress (CUMS)
Summary
The extracellular signal-regulated kinase (ERK) signaling pathway is considered to be associated with the pathogenesis and treatment of depression. We explored the role of the ERK signaling pathway in the antidepressant-like effects of acupuncture in rats exposed to chronic unpredictable mild stress (CUMS). In the last few years, studies have found that a decline in neurogenesis might be an etiological factor in depression [8, 9]. Brain-derived neurotrophic factor (BDNF) has been shown to mediate neurogenesis and synaptic plasticity, which is implicated in depression pathogenesis [10]. Some studies have proved that a decrease in ERK1/2 expression leads to depression-like behaviors in model rats
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