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

IF 4.8 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2024-10-14 DOI:10.1016/j.intimp.2024.113376

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引用次数: 0

摘要

热应激（HS）会诱发大脑的各种病理生理反应，包括神经炎症和认知障碍。虽然牛磺酸具有抗炎和增强认知能力的特性，但它在 HS 诱导的认知障碍中的作用和机制仍不清楚。本研究为暴露于 HS 的小鼠补充牛磺酸，以评估牛磺酸对 HS 诱导的小鼠模型认知功能的影响。结果发现，牛磺酸能改善小鼠HS后的认知功能障碍，减轻HS诱导的星形胶质细胞和小胶质细胞活化以及海马血脑屏障（BBB）损伤。从机理上讲，通过转录组测序确定牛磺酸能在 HS 期间调节神经元 PAS 结构域蛋白（Npas4）和脂钙蛋白 2（Lcn2）。研究发现，牛磺酸在 HS 后可通过上调 Npas4 和下调 Lcn2 来调节海马炎症并影响认知功能。随后，通过分子对接和AnimalTFDB数据库计算发现，牛磺酸可能通过调节转录因子（TFs）RE1沉默转录因子（REST）和B细胞中卡帕轻多肽基因增强子核因子1（NFKB1）来调节Npas4和Lcn2的表达。我们的研究结果表明，牛磺酸能通过Npas4和Lcn2促进HS后认知功能的恢复，为牛磺酸在临床上应用于预防或治疗HS引起的认知障碍提供了理论依据。

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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.

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

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.