Evidence map›Paper›PMID 40047959›Full record

ArticleMetabolic brain disease2025

The impact and mechanisms of YL-IPA08, a potent ligand for the translocator protein (18 kDa) on protection against LPS-induced depression and cognitive dysfunction in rodents.

Lin-Yu Cui, Jing-Yao Duan, Jiao-Zhao Yan, Jing-Ya Wang, Peng Ren, Li-Ming Zhang, Wen-Zhi Guo, Wei Dai, Yun-Feng Li

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Article in Metabolic brain disease, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

9 authors.

Lin-Yu CuiBeijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
Jing-Yao DuanBeijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
Jiao-Zhao YanLingang Laboratory, ShanghaiTech University, 555 Qiangye Road, Shanghai, 201210, China.
Jing-Ya WangBeijing Institute of Basic Medical Sciences, Beijing, 100850, China.
Peng RenShandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, Shandong, China.
Li-Ming ZhangBeijing Institute of Pharmacology and Toxicology, Beijing, 100850, China.
Wen-Zhi GuoDepartment of Anesthesiology, Seventh Medical Center of PLA General Hospital, 5 Nanmencang Road, Dongcheng, Beijing, 100070, China. elite2005gg@163.com.
Wei DaiBeijing Institute of Pharmacology and Toxicology, Beijing, 100850, China. twotou3@126.com.
Yun-Feng LiBeijing Institute of Basic Medical Sciences, Beijing, 100850, China. lyf619@aliyun.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Translocator protein (18 kDa) (TSPO) has been implicated in the development of depression and cognitive dysfunction. This study aimed to investigate the anti-depression/anti-anxiety and cognitive enhancing impacts and potential mechanisms of TSPO ligand YL-IPA08 in lipopolysaccharide (LPS)-induced inflammatory model. The effects of YL-IPA08 in LPS induced mice were identified by behavioral tests, and the target of YL-IPA08 was validated using the TSPO antagonist PK11195. The microglia in PFC were analyzed by immunofluorescence, and the inflammatory cytokines (IL-6, IL-1β and TNF-α) and anti-inflammatory factors (IL-4, IL-10, TGF-β1) in PFC was detected by ELISA or WB. Effect of TGF-β1 inhibitor Repsox on the actions of YL-IPA08 in LPS-treated mice was further verified. We found that YL-IPA08 administration ameliorated LPS-induced depression/anxiety-like behaviors and cognitive impairment, which were blocked by PK11195. YL-IPA08 reversed the increased number and inflammatory morphological changes of microglia in PFC of LPS mice by targeting TSPO. YL-IPA08 reversed the increased inflammatory cytokines (IL-6, IL-1β and TNF-α) and decreased anti-inflammatory factors (IL-4, IL-10) in the PFC of LPS mice by TSPO activation. In addition, YL-IPA08 elevated the suppressed levels of TGF-β1 and smad3 (member of TGF-β1 pathway) in PFC of LPS mice by TSPO activation. TGF-β1 inhibitor Repsox blocked the anti-depression/anxiety and cognition enhancing effects of YL-IPA08 in LPS mice. Our data implicated that central inflammation regulation and TSPO-TGF-β1/Smad pathway activation contributed to the anti-depressant/anxiety and cognitive promoting impacts of YL-IPA08.

Indexed as

Cognitive DysfunctionDepressionReceptors, GABAAnimalsCytokinesLigandsLipopolysaccharidesMaleMiceMice, Inbred C57BLMicrogliaPrefrontal CortexBzrp protein, mouseCytokinesLigandsLipopolysaccharidesReceptors, GABAAnxietyCognitive dysfunctionDepressionTransforming growth factor-β1 (TGF-β1)Translocator protein (18 kDa)

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.