Astrocyte atrophy induced by L-PGDS/PGD2/Src signaling dysfunction in the central amygdala mediates postpartum depression
文献类型：期刊论文
| 作者 | Sheng, Zhihao8; Liu, Qidong7; Song, Yujie8; Ye, Binglu5,8; Li, Yujie8; Song, Yingcai8; Liu, Jinqi3; Zhang, Bing8; Guo, Fei4,8; Xu, Zhendong8 |
| 刊名 | JOURNAL OF AFFECTIVE DISORDERS
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| 出版日期 | 2024-08-15 |
| 卷号 | 359页码:241-252 |
| 关键词 | Prostaglandin D2 Central amygdala Astrocyte atrophy Src phosphorylation Postpartum depression |
| ISSN号 | 0165-0327 |
| DOI | 10.1016/j.jad.2024.05.083 |
| 通讯作者 | Du, Weijia(duweijia@51mch.com) ; Li, Siguang(lisiguang@tongji.edu.cn) ; Liu, Zhiqiang(drliuzhiqiang@163.com) |
| 英文摘要 | Background: Postpartum depression (PPD) is a serious psychiatric disorder that has significantly adverse impacts on maternal health. Metabolic abnormalities in the brain are associated with numerous neurological disorders, yet the specific metabolic signaling pathways and brain regions involved in PPD remain unelucidated. Methods: We performed behavioral test in the virgin and postpartum mice. We used mass spectrometry imaging (MSI) and targeted metabolomics analyses to investigate the metabolic alternation in the brain of GABAAR Deltasubunit-deficient (Gabrd-/- ) postpartum mice, a specific preclinical animal model of PPD. Next, we performed mechanism studies including qPCR, Western blot, immunofluorescence staining, electron microscopy and primary astrocyte culture. In the specific knockdown and rescue experiments, we injected the adeno-associated virus into the central amygdala (CeA) of female mice. Results: We identified that prostaglandin D2 (PGD2) downregulation in the CeA was the most outstanding alternation in PPD, and then validated that lipocalin-type prostaglandin D synthase (L-PGDS)/PGD2 downregulation plays a causal role in depressive behaviors derived from PPD in both wild-type and Gabrd-/- mice. Furthermore, we verified that L-PGDS/PGD2 signaling dysfunction-induced astrocytes atrophy is mediated by Src phosphorylation both in vitro and in vivo. Limitations: L-PGDS/PGD2 signaling dysfunction may be only responsible for the depressive behavior rather than maternal behaviors in the PPD, and it remains to be seen whether this mechanism is applicable to all depression types. Conclusion: Our study identified abnormalities in the L-PGDS/PGD2 signaling in the CeA, which inhibited Src phosphorylation and induced astrocyte atrophy, ultimately resulting in the development of PPD in mice. |
| WOS关键词 | PROSTAGLANDIN D SYNTHASE ; GLIAL-CELL MIGRATION ; BRAIN ; D-2 ; ACID |
| WOS研究方向 | Neurosciences & Neurology ; Psychiatry |
| 语种 | 英语 |
| WOS记录号 | WOS:001244575900001 |
| 出版者 | ELSEVIER |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/311401]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Du, Weijia; Li, Siguang; Liu, Zhiqiang |
| 作者单位 | 1.Tongji Univ, Tongji Hosp, Stem Cell Translat Res Ctr,Orthoped Dept, Sch Med,Key Lab Spine & Spinal Cord Injury Repair, Shanghai 200065, Peoples R China 2.Tongji Univ, Shanghai Matern & Infant Hosp 1, Sch Med, Dept Anesthesiol & Crit Care, Shanghai 201204, Peoples R China 3.Univ Rochester, Rochester, NY 14627 USA 4.Chinese Acad Sci, Shanghai Inst Mat Med, Key Lab Receptor Res, Shanghai 201203, Peoples R China 5.Shanghai Jiao Tong Univ, Renji Hosp, Dept Anesthesiol, Sch Med, Shanghai 200127, Peoples R China 6.Tongji Univ, Tongji Hosp, Stem Cell Translat Res Ctr, Sch Med, Shanghai 200065, Peoples R China 7.Tongji Univ, Tongji Hosp, Sch Med,Minist Educ, Orthoped Dept,Key Lab Spine & Spinal Cord Injury R, Shanghai 200065, Peoples R China 8.Tongji Univ, Shanghai Matern & Infant Hosp 1, Shanghai Inst Maternal Fetal Med & Gynecol Oncol, Sch Med,Dept Anesthesiol,Shanghai Key Lab Maternal, Shanghai 201204, Peoples R China |
| 推荐引用方式 GB/T 7714 | Sheng, Zhihao,Liu, Qidong,Song, Yujie,et al. Astrocyte atrophy induced by L-PGDS/PGD2/Src signaling dysfunction in the central amygdala mediates postpartum depression[J]. JOURNAL OF AFFECTIVE DISORDERS,2024,359:241-252. |
| APA | Sheng, Zhihao.,Liu, Qidong.,Song, Yujie.,Ye, Binglu.,Li, Yujie.,...&Liu, Zhiqiang.(2024).Astrocyte atrophy induced by L-PGDS/PGD2/Src signaling dysfunction in the central amygdala mediates postpartum depression.JOURNAL OF AFFECTIVE DISORDERS,359,241-252. |
| MLA | Sheng, Zhihao,et al."Astrocyte atrophy induced by L-PGDS/PGD2/Src signaling dysfunction in the central amygdala mediates postpartum depression".JOURNAL OF AFFECTIVE DISORDERS 359(2024):241-252. |
入库方式： OAI收割
来源：上海药物研究所
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