TSPO activation ameliorates maternal immune activation induced PV interneuron deficits via BDNF/TrkB signaling.

IF 3.5 3区医学 Q2 NEUROSCIENCES Psychopharmacology Pub Date : 2024-12-02 DOI:10.1007/s00213-024-06728-0

Ming-Jie Mao, Hui-Ling Yu, Qing-Zhen Liu, Ya-Zhou Wen, Ming Jiang, Hong-Mei Yuan, Hua-Bei Zeng, Li-Dong Zhang, Shan-Wu Feng

{"title":"TSPO activation ameliorates maternal immune activation induced PV interneuron deficits via BDNF/TrkB signaling.","authors":"Ming-Jie Mao, Hui-Ling Yu, Qing-Zhen Liu, Ya-Zhou Wen, Ming Jiang, Hong-Mei Yuan, Hua-Bei Zeng, Li-Dong Zhang, Shan-Wu Feng","doi":"10.1007/s00213-024-06728-0","DOIUrl":null,"url":null,"abstract":"Rationale: Prenatal maternal immune activation (MIA) is an etiological risk factor for schizophrenia in offspring. Recently, parvalbumin (PV) positive interneuron deficits has been considered a critical pathology of many psych-cognitive disorders. Nevertheless, whether and how prenatal MIA affected PV interneuron in offspring remains largely unknown.Objectives: Here, we aimed to assess the relationship between MIA with PV interneuron deficits in offspring, and explored the underling mechanisms.Methods and results: Mouse model of MIA was induced using lipopolysaccharide (120 µg/kg) on gestational day 15-17. Open field, elevated plus maze, Y-Maze and novel object recognition tests were performed and local field potential was recorded on adult male offspring. PV interneuron, Translocator protein 18 kDa (TSPO), and BDNF/TrkB signaling were then evaluated. Using TPSO agonist and TrkB antagonist, the function of TSPO on PV interneuron deficits was elucidated. Our results showed that MIA induced cognitive symptoms in the adult male offspring, accompanied by down-regulated PV and TSPO expression as well as decreased theta oscillation. Notably, activating TSPO reversed MIA-induced PV interneuron defects and behavioral abnormalities. Furthermore, specific inhibition of BDNF/TrkB signaling intercepted the protective effect of TSPO activation on PV interneuron deficits.Conclusions: Our results highlight TSPO activation might prevented PV interneuron deficits and behavioral abnormalities after MIA via BDNF/TrkB signaling.","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-024-06728-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}

引用次数: 0

Abstract

Rationale: Prenatal maternal immune activation (MIA) is an etiological risk factor for schizophrenia in offspring. Recently, parvalbumin (PV) positive interneuron deficits has been considered a critical pathology of many psych-cognitive disorders. Nevertheless, whether and how prenatal MIA affected PV interneuron in offspring remains largely unknown.

Objectives: Here, we aimed to assess the relationship between MIA with PV interneuron deficits in offspring, and explored the underling mechanisms.

Methods and results: Mouse model of MIA was induced using lipopolysaccharide (120 µg/kg) on gestational day 15-17. Open field, elevated plus maze, Y-Maze and novel object recognition tests were performed and local field potential was recorded on adult male offspring. PV interneuron, Translocator protein 18 kDa (TSPO), and BDNF/TrkB signaling were then evaluated. Using TPSO agonist and TrkB antagonist, the function of TSPO on PV interneuron deficits was elucidated. Our results showed that MIA induced cognitive symptoms in the adult male offspring, accompanied by down-regulated PV and TSPO expression as well as decreased theta oscillation. Notably, activating TSPO reversed MIA-induced PV interneuron defects and behavioral abnormalities. Furthermore, specific inhibition of BDNF/TrkB signaling intercepted the protective effect of TSPO activation on PV interneuron deficits.

Conclusions: Our results highlight TSPO activation might prevented PV interneuron deficits and behavioral abnormalities after MIA via BDNF/TrkB signaling.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

TSPO激活通过BDNF/TrkB信号通路改善母体免疫激活诱导的PV中间神经元缺陷。

理由：产前母体免疫激活（MIA）是后代精神分裂症的一个病因危险因素。近年来，小白蛋白（PV）阳性的中间神经元缺陷被认为是许多心理认知障碍的重要病理。然而，产前MIA是否以及如何影响后代PV中间神经元仍是未知的。目的：在这里，我们旨在评估MIA与后代PV中间神经元缺陷之间的关系，并探讨其潜在机制。方法与结果：采用脂多糖（120µg/kg）在妊娠15 ~ 17天诱导小鼠MIA模型。对成年雄性子代进行开放场、高架加迷宫、y型迷宫和新型目标识别实验，并记录局部场电位。然后评估PV中间神经元，转运蛋白18 kDa （TSPO）和BDNF/TrkB信号传导。利用TPSO激动剂和TrkB拮抗剂，阐明了TSPO在PV中间神经元缺陷中的作用。我们的研究结果表明，MIA诱导成年雄性后代出现认知症状，并伴有PV和TSPO表达下调以及θ波振荡减少。值得注意的是，激活TSPO可以逆转mia诱导的PV中间神经元缺陷和行为异常。此外，BDNF/TrkB信号的特异性抑制阻断了TSPO激活对PV中间神经元缺陷的保护作用。结论：我们的研究结果强调TSPO激活可能通过BDNF/TrkB信号阻止MIA后PV中间神经元缺陷和行为异常。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Psychopharmacology 医学-精神病学

CiteScore

7.10

自引率

5.90%

发文量

257

审稿时长

2-4 weeks

期刊介绍： Official Journal of the European Behavioural Pharmacology Society (EBPS) Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields: Human Psychopharmacology: Experimental This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered. Human Psychopharmacology: Clinical and Translational This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects. Preclinical psychopharmacology: Behavioral and Neural This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels. Preclinical Psychopharmacology: Translational This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways. Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.