Maresin-1 improves LPS-induced depressive-like behavior by inhibiting hippocampal microglial activation

作者全名："Shi, Lei; Xia, Zhu; Guo, Jiamei; Wang, Lixia; Peng, Zhiping; Qiu, Dachuan; Zhou, Yi; Zhou, Dongdong; Kuang, Li; Qiu, Tian"

作者地址："[Shi, Lei; Guo, Jiamei; Wang, Lixia; Zhou, Yi; Kuang, Li; Qiu, Tian] Chongqing Med Univ, Affiliated Hosp 1, Dept Psychiat, Chongqing 400016, Peoples R China; [Xia, Zhu] Chongqing Med Univ, Affiliated Hosp 1, Dept Nucl Med, Chongqing, Peoples R China; [Peng, Zhiping; Qiu, Dachuan] Chongqing Med Univ, Coll Basic Med, Dept Radiol Med, Chongqing, Peoples R China; [Zhou, Dongdong] Chongqing Med Univ, Univ Town Hosp, Mental Hlth Ctr, Chongqing, Peoples R China; [Qiu, Tian] Chongqing Med Univ, Affiliated Hosp 1, Dept Psychiat, YiXueYuan Rd, Chongqing, Peoples R China"

通信作者："Qiu, T (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Psychiat, YiXueYuan Rd, Chongqing, Peoples R China."

来源：JOURNAL OF AFFECTIVE DISORDERS

ESI学科分类：PSYCHIATRY/PSYCHOLOGY

WOS号：WOS:000949858400001

JCR分区：Q1

影响因子：6.6

年份：2023

卷号：328

期号：　

开始页：261

结束页：272

文献类型：Article

关键词：Depression; Anti -inflammation; Microglia; PET -CT; Maresin-1; RNA-seq

摘要："Maresin-1 is an antiphlogistic agonist synthesized by macrophages from docosahexaenoic acid (DHA). It has both anti-inflammatory and pro-inflammatory properties and has been found to enhance neuroprotection and cognitive function. However, there is limited knowledge of its effects on depression and the potential mechanism remains unclear. In this study, the effects of Maresin-1 on lipopolysaccharide (LPS)-induced depressive symptoms and neuroinflammation were investigated in mice and the possible cellular and molecular mechanisms were further clarified. Maresin-1 treatment (5 mu g/kg, i.p.) led to improved tail suspension times, as well as distances moved in an open-field test but it did not improve reductions in sugar-water consumption in mice with depressive-like behaviors induced by LPS (1 mg/kg, i.p.); TSPO PET-CT scanning showed that Maresin-1 reduced the standardized uptake value (SUV) of [18 F] DPA-714 in brain regions associated with depression (e.g., hippocampus and pre-frontal cortex), while immunofluorescence of hippocampal and indicated that Maresin-1 inhibited microglial activation reducing the expression of the pro-inflammatory cytokine IL-113 and NLRP3. The RNA sequencing of mouse hippocampi showed that genes expressed differentially between Maresin-1-treated and LPS-treated tissue were associated with tight connections between cells and the stress-activated MAPK cascade negative regulatory pathways. Overall, this study demonstrates that peripheral application of Maresin-1 could partially relieve LPS-induced depressive-like behaviors and showed for the first time that this effect was related to its anti-inflammatory action on microglia, thus providing new clues for the pharmacological mechanism underlying the anti-depression properties of Maresin-1."

基金机构：Chongqing Municipal Science and Technology Commission [CSTC2021-jscx-gksb-N0002]

基金资助正文：This study is funded by the Chongqing Municipal Science and Technology Commission Key Project: CSTC2021-jscx-gksb-N0002.