Acupuncture Ameliorates Depression-Like Behaviors Through Modulating the Neuroinflammation Mediated by TLR4 Signaling Pathway in Rats Exposed to Chronic Restraint Stress

Mol Neurobiol. 2024 May;61(5):2606-2619. doi: 10.1007/s12035-023-03737-6. Epub 2023 Nov 2.

Abstract

Recently, emerging evidence has identified that stress-induced activation of neuroinflammation is considered to be one of the most prevalently precipitating factors in the pathogenesis of depression. Data from clinical trials and experimental findings has verified the efficacy and safety of acupuncture in the prevention and treatment of depression. However, the mechanism of the preventive effect of acupuncture for depression has not been fully elucidated. The current study aimed to investigate the preventive effect and mechanism of acupuncture through modulating the neuroinflammation mediated by toll-like receptor 4 (TLR4) signaling pathway in rats exposed to chronic restraint stress (CRS). All rats were subjected to CRS for 21 days, with the exception of rats in control group. One hour before CRS, rats in acupuncture group were exposed to acupuncture at Baihui (GV20) and Yintang (GV29). The depression-like behaviors were evaluated by body weight assessment and sucrose preference test at 0, 7, 14, and 21 days. The expression of activated microglia in hippocampus was detected by immunofluorescence. The expression of key proteins on TLR4 signaling pathway of TLR4, MyD88, TRAF6, NF-κB p65, TNF-α, and mRNA of TLR4 in the hippocampus was detected by western blot and real-time quantitative polymerase chain reaction to investigate the effect of acupuncture on stress-induced activation of neuroinflammation. The present study provided evidence that acupuncture exerted potential preventive effect that might be mediated in part by suppressing the neuroinflammation induced by TLR4 signaling pathway, which may be a promising treatment target to improve current treatments for depression.

Keywords: Acupuncture; Depression; Microglia; Neuroinflammation; Stress; TLR4 signaling pathway.

MeSH terms

  • Acupuncture Therapy* / methods
  • Animals
  • Behavior, Animal
  • Depression* / etiology
  • Depression* / metabolism
  • Depression* / therapy
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Male
  • Microglia / metabolism
  • Myeloid Differentiation Factor 88 / metabolism
  • Neuroinflammatory Diseases / metabolism
  • Rats
  • Rats, Sprague-Dawley*
  • Restraint, Physical* / adverse effects
  • Restraint, Physical* / psychology
  • Signal Transduction*
  • Stress, Psychological* / complications
  • Stress, Psychological* / therapy
  • Toll-Like Receptor 4* / metabolism

Substances

  • Myeloid Differentiation Factor 88
  • Tlr4 protein, rat
  • Toll-Like Receptor 4