The effect of acupuncture on lateral habenular nucleus and intestinal microflora in depression model rats

Wenjie Chen; Yiping Chen; Muhammad Shahzad Aslam; Junliang Shen; Tao Tong; Simin Yan; Wenjing Cheng; Zichun Huang; Jiawei Li; Siyu Liu; Jianguo Li; Jingyu Zeng; Meng Li; Zhuoran You; Xianjun Meng

doi:10.1016/j.bbr.2023.114627

The effect of acupuncture on lateral habenular nucleus and intestinal microflora in depression model rats

Behav Brain Res. 2023 Oct 18:455:114627. doi: 10.1016/j.bbr.2023.114627. Epub 2023 Aug 22.

Authors

Wenjie Chen¹, Yiping Chen², Muhammad Shahzad Aslam³, Junliang Shen¹, Tao Tong⁴, Simin Yan¹, Wenjing Cheng⁵, Zichun Huang¹, Jiawei Li¹, Siyu Liu⁶, Jianguo Li⁴, Jingyu Zeng¹, Meng Li⁴, Zhuoran You⁴, Xianjun Meng⁷

Affiliations

¹ Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, Fujian, PR China.
² First Clinical College, Yunnan University of Chinese Medicine, Kunming, Yunnan, PR China.
³ School of Traditional Chinese Medicine, Xiamen University Malaysia, Sepang, Malaysia.
⁴ Second Clinical College, Shanxi University of Traditional Chinese Medicine, Taiyuan, Shanxi, PR China.
⁵ Department of Rehabilitation Medicine, Ezhou Central Hospital, Ezhou, Hubei, PR China.
⁶ Department of Acupuncture, Longyan Hospital of Traditional Chinese Medicine, Longyan, Fujian, PR China.
⁷ Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, Fujian, PR China; Traditional Chinese Medicine Foundation of Xiamen, Xiamen, Fujian, PR. China. Electronic address: mengxianjun@xmu.edu.cn.

PMID: 37619770
DOI: 10.1016/j.bbr.2023.114627

Abstract

Background: Depression is a severe emotional condition that significantly affects the quality of life. Acupuncture exerts preventive effects on depression in rats with post-chronic unpredictable mild stress (CUMS). Methods The study involved chronic unpredictable mild stress (CUMS) depression model mice to administer acupuncture as a preventative measure to investigate the mechanism of acupuncture's antidepressant and observe the effect of acupuncture on impact via the Lateral Habenula (LHb) and Gut-Liver-Brain Axis. The researcher investigated molecules correlating with a nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway and assessed inflammation in the LHb and liver. In addition, 16 S rDNA bioinformatics study revealed the quantity and variety of gut microbiota. Rats were randomly divided into five groups: control (CON), CUMS, CUMS + acupuncture (AP), CUMS + fluoxetine (FX) and CUMS + N(G) -nitro -L- arginine methyl ester (LNAME) group. Except for the CON group, other rats were exposed to CUMS condition for 28 days. Simultaneously, manual acupuncture (at Fengfu and Shangxing acupoints, once every other day) and fluoxetine gavage (2.1 mg/kg, 0.21 mg/mL, daily) were conducted to the groups of AP and FX, respectively, after stressors. Rats in LNAME group were treated with LNAME normal saline (10 mg/kg, 1 mg/mL, i.p.) solution. Behavioural tests and biological detection methods were conducted sequentially to evaluate depressionlike phenotype in rats.

Results: The results showed CUMS induced depression-like behaviours, hyper-activation of NO/cGMP signaling pathway, inflammation in serum, LHb and liver, and dysbiosis of the gut microbiota. These changes could be prevented and ameliorated by acupuncture to varying extents.

Conclusion: Acupuncture prevented and attenuated depression-like phenotype induced by CUMS, possibly via regulating the NO/cGMP signaling pathway and thus improving inflammation in serum, LHb and liver, and gut microbiota dysbiosis. In addition, these can be evidence of the existence of the gut-liver-brain axis.

Keywords: Acupuncture; Depression; Gut-liver-brain axis; Inflammation; Lateral habenula; Nitric oxide/cyclic-guanosine monophosphate pathway.