Liyi Wang, Han Guo, Weidong Zhao, Jiahao Wang, Xuhua Cao
{"title":"奥拉西坦通过竞争性内源性RNA调控网络改善创伤性脑损伤后神经功能。","authors":"Liyi Wang, Han Guo, Weidong Zhao, Jiahao Wang, Xuhua Cao","doi":"10.1007/s00213-025-06797-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Rationale: </strong>Oxiracetam (ORC) has been demonstrated to improve neurological function resulting from traumatic brain injury (TBI).</p><p><strong>Objectives: </strong>This study aims to explore the precise molecular mechanism of ORC in the treatment of TBI.</p><p><strong>Methods: </strong>TBI rat model was established and treated with ORC. Modified Garcia score, rotarod test and HE staining were employed to evaluate the neuroprotective effects of ORC. Subsequently, RNA-seq was conducted on the hippocampus of sham, TBI and ORC rats to identify differential expression (DE) lncRNAs and mRNAs. Functional analysis of DE lncRNAs and mRNAs was performed. The real-time quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of DE lncRNAs and DE mRNAs. Western blot was performed to explore important pathway in ceRNA networks.</p><p><strong>Results: </strong>ORC has been demonstrated to effectively improve neurological function in TBI rats. A total of 10 ORC-treated DE lncRNAs and 61 DE mRNAs were obtained. A co-expression network comprising 79 lncRNA-mRNA pairs associated with the treatment of ORC was constructed. Furthermore, an lncRNA-miRNA-mRNA regulated ceRNA network was constructed, comprising 15 mRNAs, 41 miRNAs and 10 lncRNAs. Functional enrichment, qRT-PCR, and Western blot analysis showed that ORC improve neurological function of TBI rats by regulating multiple signaling pathways, including the JAK-STAT/PI3K-Akt pathway, as well as affecting the expression of key genes Prlr, Cdkn1a, and Cldn1.</p><p><strong>Conclusion: </strong>Our study reveals the mechanism of ORC therapy in TBI rats, which mainly relies on the regulation of the JAK-STAT/PI3K-Akt pathway and the influence on the expression of key genes Prlr, Cdkn1a, and Cldn1.</p>","PeriodicalId":20783,"journal":{"name":"Psychopharmacology","volume":" ","pages":""},"PeriodicalIF":3.5000,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Oxiracetam ameliorates neurological function after traumatic brain injury through competing endogenous RNA regulatory network.\",\"authors\":\"Liyi Wang, Han Guo, Weidong Zhao, Jiahao Wang, Xuhua Cao\",\"doi\":\"10.1007/s00213-025-06797-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Rationale: </strong>Oxiracetam (ORC) has been demonstrated to improve neurological function resulting from traumatic brain injury (TBI).</p><p><strong>Objectives: </strong>This study aims to explore the precise molecular mechanism of ORC in the treatment of TBI.</p><p><strong>Methods: </strong>TBI rat model was established and treated with ORC. Modified Garcia score, rotarod test and HE staining were employed to evaluate the neuroprotective effects of ORC. Subsequently, RNA-seq was conducted on the hippocampus of sham, TBI and ORC rats to identify differential expression (DE) lncRNAs and mRNAs. Functional analysis of DE lncRNAs and mRNAs was performed. The real-time quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of DE lncRNAs and DE mRNAs. Western blot was performed to explore important pathway in ceRNA networks.</p><p><strong>Results: </strong>ORC has been demonstrated to effectively improve neurological function in TBI rats. A total of 10 ORC-treated DE lncRNAs and 61 DE mRNAs were obtained. A co-expression network comprising 79 lncRNA-mRNA pairs associated with the treatment of ORC was constructed. Furthermore, an lncRNA-miRNA-mRNA regulated ceRNA network was constructed, comprising 15 mRNAs, 41 miRNAs and 10 lncRNAs. Functional enrichment, qRT-PCR, and Western blot analysis showed that ORC improve neurological function of TBI rats by regulating multiple signaling pathways, including the JAK-STAT/PI3K-Akt pathway, as well as affecting the expression of key genes Prlr, Cdkn1a, and Cldn1.</p><p><strong>Conclusion: </strong>Our study reveals the mechanism of ORC therapy in TBI rats, which mainly relies on the regulation of the JAK-STAT/PI3K-Akt pathway and the influence on the expression of key genes Prlr, Cdkn1a, and Cldn1.</p>\",\"PeriodicalId\":20783,\"journal\":{\"name\":\"Psychopharmacology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.5000,\"publicationDate\":\"2025-04-24\",\"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/s00213-025-06797-9\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Psychopharmacology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00213-025-06797-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
Oxiracetam ameliorates neurological function after traumatic brain injury through competing endogenous RNA regulatory network.
Rationale: Oxiracetam (ORC) has been demonstrated to improve neurological function resulting from traumatic brain injury (TBI).
Objectives: This study aims to explore the precise molecular mechanism of ORC in the treatment of TBI.
Methods: TBI rat model was established and treated with ORC. Modified Garcia score, rotarod test and HE staining were employed to evaluate the neuroprotective effects of ORC. Subsequently, RNA-seq was conducted on the hippocampus of sham, TBI and ORC rats to identify differential expression (DE) lncRNAs and mRNAs. Functional analysis of DE lncRNAs and mRNAs was performed. The real-time quantitative polymerase chain reaction (qRT-PCR) was used to determine the expression of DE lncRNAs and DE mRNAs. Western blot was performed to explore important pathway in ceRNA networks.
Results: ORC has been demonstrated to effectively improve neurological function in TBI rats. A total of 10 ORC-treated DE lncRNAs and 61 DE mRNAs were obtained. A co-expression network comprising 79 lncRNA-mRNA pairs associated with the treatment of ORC was constructed. Furthermore, an lncRNA-miRNA-mRNA regulated ceRNA network was constructed, comprising 15 mRNAs, 41 miRNAs and 10 lncRNAs. Functional enrichment, qRT-PCR, and Western blot analysis showed that ORC improve neurological function of TBI rats by regulating multiple signaling pathways, including the JAK-STAT/PI3K-Akt pathway, as well as affecting the expression of key genes Prlr, Cdkn1a, and Cldn1.
Conclusion: Our study reveals the mechanism of ORC therapy in TBI rats, which mainly relies on the regulation of the JAK-STAT/PI3K-Akt pathway and the influence on the expression of key genes Prlr, Cdkn1a, and Cldn1.
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.
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