{"title":"牛磺酸通过 Npas4 和 Lcn2 对热应激诱导的认知障碍具有保护作用","authors":"","doi":"10.1016/j.intimp.2024.113376","DOIUrl":null,"url":null,"abstract":"<div><div>Heat stress (HS) induces various pathophysiological responses in the brain, encompassing neuroinflammation and cognitive impairments. Although taurine has been reported to possess anti-inflammatory and cognitive-enhancing properties, its role and mechanisms in HS-induced cognitive impairment remain unclear. This study supplemented mice exposed to HS with taurine to assess its effect on cognitive function in a HS-induced mouse model. The results revealed that taurine ameliorated cognitive deficits following HS in mice and mitigated HS-induced astrocyte and microglia activation as well as blood–brain barrier (BBB) damage in the hippocampus. Mechanistically, Mechanistically, transcriptome sequencing was employed to identify that taurine regulates neuronal PAS domain protein (<em>Npas4</em>) and lipocalin 2 (<em>Lcn2</em>) during HS. Taurine was found to modulate hippocampal inflammation and influence cognitive function by upregulating <em>Npas4</em> and downregulating <em>Lcn2</em> after HS. Subsequently, molecular docking and AnimalTFDB database calculations were conducted, revealing that taurine might regulate the expression of <em>Npas4</em> and <em>Lcn2</em> by modulating the regulatory transcription factors (TFs) RE1 silencing transcription factor (REST) and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1). Our findings demonstrate that taurine enhances the recovery of cognitive function through <em>Npas4</em> and <em>Lcn2</em> following HS, providing a theoretical basis for the clinical application of taurine in preventing or treating HS-induced cognitive impairment.</div></div>","PeriodicalId":13859,"journal":{"name":"International immunopharmacology","volume":null,"pages":null},"PeriodicalIF":4.8000,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Protective effects of taurine on heat Stress-Induced cognitive impairment through Npas4 and Lcn2\",\"authors\":\"\",\"doi\":\"10.1016/j.intimp.2024.113376\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Heat stress (HS) induces various pathophysiological responses in the brain, encompassing neuroinflammation and cognitive impairments. Although taurine has been reported to possess anti-inflammatory and cognitive-enhancing properties, its role and mechanisms in HS-induced cognitive impairment remain unclear. This study supplemented mice exposed to HS with taurine to assess its effect on cognitive function in a HS-induced mouse model. The results revealed that taurine ameliorated cognitive deficits following HS in mice and mitigated HS-induced astrocyte and microglia activation as well as blood–brain barrier (BBB) damage in the hippocampus. Mechanistically, Mechanistically, transcriptome sequencing was employed to identify that taurine regulates neuronal PAS domain protein (<em>Npas4</em>) and lipocalin 2 (<em>Lcn2</em>) during HS. Taurine was found to modulate hippocampal inflammation and influence cognitive function by upregulating <em>Npas4</em> and downregulating <em>Lcn2</em> after HS. Subsequently, molecular docking and AnimalTFDB database calculations were conducted, revealing that taurine might regulate the expression of <em>Npas4</em> and <em>Lcn2</em> by modulating the regulatory transcription factors (TFs) RE1 silencing transcription factor (REST) and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1). Our findings demonstrate that taurine enhances the recovery of cognitive function through <em>Npas4</em> and <em>Lcn2</em> following HS, providing a theoretical basis for the clinical application of taurine in preventing or treating HS-induced cognitive impairment.</div></div>\",\"PeriodicalId\":13859,\"journal\":{\"name\":\"International immunopharmacology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2024-10-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International immunopharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1567576924018988\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International immunopharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1567576924018988","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Protective effects of taurine on heat Stress-Induced cognitive impairment through Npas4 and Lcn2
Heat stress (HS) induces various pathophysiological responses in the brain, encompassing neuroinflammation and cognitive impairments. Although taurine has been reported to possess anti-inflammatory and cognitive-enhancing properties, its role and mechanisms in HS-induced cognitive impairment remain unclear. This study supplemented mice exposed to HS with taurine to assess its effect on cognitive function in a HS-induced mouse model. The results revealed that taurine ameliorated cognitive deficits following HS in mice and mitigated HS-induced astrocyte and microglia activation as well as blood–brain barrier (BBB) damage in the hippocampus. Mechanistically, Mechanistically, transcriptome sequencing was employed to identify that taurine regulates neuronal PAS domain protein (Npas4) and lipocalin 2 (Lcn2) during HS. Taurine was found to modulate hippocampal inflammation and influence cognitive function by upregulating Npas4 and downregulating Lcn2 after HS. Subsequently, molecular docking and AnimalTFDB database calculations were conducted, revealing that taurine might regulate the expression of Npas4 and Lcn2 by modulating the regulatory transcription factors (TFs) RE1 silencing transcription factor (REST) and nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 (NFKB1). Our findings demonstrate that taurine enhances the recovery of cognitive function through Npas4 and Lcn2 following HS, providing a theoretical basis for the clinical application of taurine in preventing or treating HS-induced cognitive impairment.
期刊介绍:
International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome.
The subject material appropriate for submission includes:
• Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders.
• Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state.
• Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses.
• Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action.
• Agents that activate genes or modify transcription and translation within the immune response.
• Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active.
• Production, function and regulation of cytokines and their receptors.
• Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.