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姜黄素治疗可改善海湾战争病模型的认知和情绪功能，增强神经发生，并减轻海马体的炎症和线粒体功能障碍。

Curcumin treatment leads to better cognitive and mood function in a model of Gulf War Illness with enhanced neurogenesis, and alleviation of inflammation and mitochondrial dysfunction in the hippocampus.

机构信息

Olin E. Teague Veterans' Medical Center, Central Texas Veterans Health Care System, Temple, TX, USA; Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine, Temple and College Station, TX, USA; Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, TX, USA.

Olin E. Teague Veterans' Medical Center, Central Texas Veterans Health Care System, Temple, TX, USA; Institute for Regenerative Medicine, Texas A&M Health Science Center College of Medicine, Temple and College Station, TX, USA; Department of Molecular and Cellular Medicine, Texas A&M Health Science Center College of Medicine, College Station, TX, USA.

出版信息

Brain Behav Immun. 2018 Mar;69:499-514. doi: 10.1016/j.bbi.2018.01.009. Epub 2018 Feb 15.

DOI:10.1016/j.bbi.2018.01.009
PMID:29454881
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7023905/
Abstract

Diminished cognitive and mood function are among the most conspicuous symptoms of Gulf War Illness (GWI). Our previous studies in a rat model of GWI have demonstrated that persistent cognitive and mood impairments are associated with substantially declined neurogenesis, chronic low-grade inflammation, increased oxidative stress and mitochondrial dysfunction in the hippocampus. We tested the efficacy of curcumin (CUR) to maintain better cognitive and mood function in a rat model of GWI because of its neurogenic, antiinflammatory, antioxidant, and memory and mood enhancing properties. Male rats were exposed daily to low doses of GWI-related chemicals, pyridostigmine bromide, N,N-diethyl-m-toluamide (DEET) and permethrin, and 5-minutes of restraint stress for 28 days. Animals were next randomly assigned to two groups, which received daily CUR or vehicle treatment for 30 days. Animals also received 5'-bromodeoxyuridine during the last seven days of treatment for analysis of neurogenesis. Behavioral studies through object location, novel object recognition and novelty suppressed feeding tests performed sixty days after treatment revealed better cognitive and mood function in CUR treated GWI rats. These rats also displayed enhanced neurogenesis and diminished inflammation typified by reduced astrocyte hypertrophy and activated microglia in the hippocampus. Additional studies showed that CUR treatment to GWI rats enhanced the expression of antioxidant genes and normalized the expression of multiple genes related to mitochondrial respiration. Thus, CUR therapy is efficacious for maintaining better memory and mood function in a model of GWI. Enhanced neurogenesis, restrained inflammation and oxidative stress with normalized mitochondrial respiration may underlie better memory and mood function mediated by CUR treatment.

摘要

认知和情绪功能下降是海湾战争病 (GWI) 最明显的症状之一。我们之前在 GWI 大鼠模型中的研究表明，持续的认知和情绪障碍与海马体中的神经发生显著减少、慢性低度炎症、氧化应激和线粒体功能障碍有关。由于姜黄素 (CUR) 具有神经发生、抗炎、抗氧化以及增强记忆和情绪的特性，我们测试了 CUR 维持 GWI 大鼠更好的认知和情绪功能的功效。雄性大鼠每天暴露于低剂量与 GWI 相关的化学物质，即溴化吡斯的明、N,N-二乙基间甲苯酰胺 (DEET) 和氯菊酯，以及 5 分钟的束缚应激，共 28 天。动物随后被随机分为两组，分别接受 CUR 或载体治疗 30 天。动物还在治疗的最后七天接受 5'-溴脱氧尿苷处理，以分析神经发生。治疗后 60 天进行的物体位置、新物体识别和新异抑制进食测试的行为研究表明，CUR 治疗的 GWI 大鼠具有更好的认知和情绪功能。这些大鼠还显示出增强的神经发生和炎症减少，其特征是海马体中的星形胶质细胞肥大和激活的小胶质细胞减少。进一步的研究表明，CUR 治疗 GWI 大鼠可增强抗氧化基因的表达并使与线粒体呼吸相关的多个基因的表达正常化。因此，CUR 治疗对维持 GWI 模型中的记忆和情绪功能有效。增强的神经发生、受抑制的炎症和氧化应激以及正常的线粒体呼吸可能是 CUR 治疗介导更好的记忆和情绪功能的基础。

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