Abstract
The neuroprotective effect of electroacupuncture (EA) treatment has been well studied; growing evidence suggests that changes in lipid composition may be involved in the pathogenesis of post-traumatic stress disorder (PTSD) and may be a target for treatment. However, the influence of early EA intervention on brain lipid composition in patients with PTSD has never been investigated. Using a modified single prolonged stress (mSPS) model in mice, we assessed the anti-PTSD-like effects of early intervention using EA and evaluated changes in lipid composition in the hippocampus and prefrontal cortex (PFC) using a mass spectrometry-based lipidomic approach. mSPS induced changes in lipid composition in the hippocampus, notably in the content of sphingolipids, glycerolipids, and fatty acyls. These lipid changes were more robust than those observed in the PFC. Early intervention with EA after mSPS ameliorated PTSD-like behaviors and partly normalized mSPS-induced lipid changes, notably in the hippocampus. Cumulatively, our data suggest that EA may reverse mSPS-induced PTSD-like behaviors due to region-specific regulation of the brain lipidome, providing new insights into the therapeutic mechanism of EA.
Highlights
Post-traumatic stress disorder is a stressor-related disorder characterized by avoidance, re-experiencing of trauma, and hyperarousal symptoms, and affects approximately 7–10% of the general population (Steenkamp et al, 2015; Careaga et al, 2016; O’Donovan et al, 2017)
Two-way analysis of variance (ANOVA) revealed that modified single prolonged stress (mSPS) and EA treatment did not induce any motor impairment in mice because in the open field test (OFT), we observed no significant differences in the total distance traveled in either the mSPS or the EA treatment factors Figures 1B,C)
Significant differences were observed in the time spent in the center squares of the OFT, time spent in the open arms of the elevated-plus maze test (EPMT), as well as freezing time in both contextual fear and cued fear test between the four groups (Figures 1D–H and Supplementary Table S1)
Summary
Post-traumatic stress disorder is a stressor-related disorder characterized by avoidance, re-experiencing of trauma, and hyperarousal symptoms, and affects approximately 7–10% of the general population (Steenkamp et al, 2015; Careaga et al, 2016; O’Donovan et al, 2017). PTSD is often associated with other psychiatric symptoms and functional impairment, such as depression, sleep disorders, anorexia as well as an increased risk of dementia and vascular neurodegenerative diseases (Song et al, 2020; Trottier et al, 2021). Selective serotonin reuptake inhibitors (SSRIs), such as paroxetine and sertraline are the first-line pharmacotherapy that has been shown to relieve PTSD symptoms including sleep problems, nightmares, anxiety and depression. These agents rarely induce remission and their benefits decline over time and might carry a risk of withdrawal syndromes and relapse (Mello et al, 2013; Shalev et al, 2017; Sbarski and Akirav, 2020). Investigation of the pathogenesis of PTSD and the development of new approaches for treating it are urgently needed (Krystal et al, 2017; Fenster et al, 2018)
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