Abstract

Depression is a serious psychiatric disorder with an enormous socioeconomic burden, and it is commonly comorbid with pain, chronic fatigue, or other inflammatory diseases. Recent studies have shown that acupuncture is an effective therapeutic method for reducing depressive symptoms; however, the underlying mechanism remains unknown. In this study, we investigated the effects of acupuncture on chronic stress-induced depression-like behavior and its central neural mechanisms in the brain. We induced chronic restraint stress (CRS) in male C57BL/6 mice for 14 or 28 consecutive days. Acupuncture treatment was performed at KI10·LR8·LU8·LR4 or control points for 7 or 14 days. Depression-like behavior was assessed with the open field test. Then, brain neural activity involving c-Fos and serotonin-related mechanisms via the 5-HT1A and 5-HT1B receptors were investigated. Acupuncture treatment at KI10·LR8·LU8·LR4 points rescued the depressive-like behavior, while control points (LU8·LR4·HT8·LR2) and non-acupoints on the hips did not. Brain neural activity was changed in the hippocampus, cingulate cortex, motor cortex, insular cortex, thalamus, and the hypothalamus after acupuncture treatment. Acupuncture treatment increased expression of 5-HT1A receptor in the cortex, hippocampus, thalamus, and the hypothalamus, and of 5-HT1B in the cortex and thalamus. In conclusion, acupuncture treatment at KI10·LR8·LU8·LR4 was effective in alleviating the depressive-like behavior in mice, and this therapeutic effect was produced through central brain neural activity and serotonin receptor modulation.

Highlights

  • Depression is a common mood disorder, which has a high mortality and recurrence rate (Reddy, 2010)

  • In the chronic restraint stress (CRS), AP, and NP groups, c-Fos expression in the HyTH-VM showed a positive correlation with the total distance travelled in the open field test (p < 0.01) (Figure 5E). These results indicated that the cortex, hippocampus, thalamus, and the hypothalamus, which were the only regions changed by AP treatment, were the main regions mediating the therapeutic effect of acupuncture treatment

  • To the best of our knowledge, this study is the first to identify the effect of acupoint combination of KI10·LR8·LU8·LR4 in chronic stress-induced depressive-like behavior and its neural mechanism

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Summary

Introduction

Depression is a common mood disorder, which has a high mortality and recurrence rate (Reddy, 2010). Depression is a serious disease per se and has a major impact on the occurrence of other conditions, such as Effects of Acupuncture on Chronic Stress pain (Bair et al, 2003; Goldenberg, 2010), chronic fatigue syndrome (Bram et al, 2018), neurodegenerative disease (Modrego and Ferrández, 2004), and inflammatory diseases (Baerwald et al, 2019). The etiology of depression involves genetic, environmental, socioeconomic, and stress-related factors (Dunn et al, 2015). As stress is emerging as a major cause of depression (Yang et al, 2015), there is an interest in developing treatment methods for depression and elucidating the pathological and neurobiological mechanism of stress-induced depression. Much of the fundamental mechanisms of stressinduced depression have yet to be elucidated

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