Microglial Function during Glucose Deprivation: Inflammatory and Neuropsychiatric Implications.
Microglial Function during Glucose Deprivation: Inflammatory and Neuropsychiatric Implications.
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DOI：
10.1007/s12035-017-0422-9
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发表时间：
2018-03
影响因子：
5.1
通讯作者：
Todd KG
中科院分区：
文献类型：
--
作者：
Churchward MA;Tchir DR;Todd KG
炎症越来越多地被认为是神经精神障碍（包括抑郁症、焦虑症和自闭症）的病理生理学的贡献者，尽管在病理条件下导致背景不适当或持续炎症的因素尚未阐明。小胶质细胞作为中枢神经系统炎症的关键介质，是引发病理性炎症的可能候选者，也是治疗干预的理想点。葡萄糖剥夺，作为缺血的病理生理学的组成部分或在糖尿病中短暂发生，可能有助于改变小胶质细胞功能，从而导致炎症损伤。为此，从出生后的大鼠脑中培养原代小胶质细胞，并在体外进行葡萄糖剥夺。小胶质细胞的特征在于它们的增殖，吞噬功能和炎症因子的分泌，并测试它们对强有力的炎症刺激的反应能力。在没有葡萄糖的情况下，小胶质细胞仍然能够增殖，吞噬和炎症激活，并表现出增加的炎症因子的释放后，呈现的炎症刺激。葡萄糖剥夺的小胶质细胞表现出增加的吞噬活性和减少的脂质在脂滴中的积累超过48小时的时间过程中，这表明他们可能会使用清除的脂质作为一个关键的替代能源在代谢应激。在目前的手稿中，我们提出了新的发现，葡萄糖剥夺可能敏感的小胶质细胞释放炎症介质和总理小胶质细胞的功能，生存和炎症的作用，这可能有助于缺血，糖尿病和/或代谢紊乱的精神共病。本文的在线版本（doi：10.1007/s12035-017-0422-9）包含补充材料，可供授权用户使用。
Inflammation is increasingly recognized as a contributor to the pathophysiology of neuropsychiatric disorders, including depression, anxiety disorders and autism, though the factors leading to contextually inappropriate or sustained inflammation in pathological conditions are yet to be elucidated. Microglia, as the key mediators of inflammation in the CNS, serve as likely candidates in initiating pathological inflammation and as an ideal point of therapeutic intervention. Glucose deprivation, as a component of the pathophysiology of ischemia or occurring transiently in diabetes, may serve to modify microglial function contributing to inflammatory injury. To this end, primary microglia were cultured from postnatal rat brain and subject to glucose deprivation in vitro. Microglia were characterized for their proliferation, phagocytic function and secretion of inflammatory factors, and tested for their capacity to respond to a potent inflammatory stimulus. In the absence of glucose, microglia remained capable of proliferation, phagocytosis and inflammatory activation and showed increased release of inflammatory factors after presentation of an inflammatory stimulus. Glucose-deprived microglia demonstrated increased phagocytic activity and decreased accumulation of lipids in lipid droplets over a 48-h timecourse, suggesting they may use scavenged lipids as a key alternate energy source during metabolic stress. In the present manuscript, we present novel findings that glucose deprivation may sensitize microglial release of inflammatory mediators and prime microglial functions for both survival and inflammatory roles, which may contribute to psychiatric comorbidities of ischemia, diabetes and/or metabolic disorder. The online version of this article (doi:10.1007/s12035-017-0422-9) contains supplementary material, which is available to authorized users.
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影响因子：
--
作者：
COULEHAN, JL;SCHULBERG, HC;ARENA, VC
通讯作者：
ARENA, VC
DOI：
10.1016/s1387-2656(05)11004-7
发表时间：
2005-01-01
期刊：
BIOTECHNOLOGY ANNUAL REVIEW, VOL 11
影响因子：
--
作者：
Berridge, MV;Herst, PM;Tan, AS
通讯作者：
Tan, AS
影响因子：
3.6
作者：
Churchward MA;Todd KG
通讯作者：
Todd KG
影响因子：
64.5
作者：
Chang CH;Curtis JD;Maggi LB Jr;Faubert B;Villarino AV;O'Sullivan D;Huang SC;van der Windt GJ;Blagih J;Qiu J;Weber JD;Pearce EJ;Jones RG;Pearce EL
通讯作者：
Pearce EL
影响因子：
6.2
作者：
Eyo, Ukpong;Dailey, Michael E.
通讯作者：
Dailey, Michael E.