Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
Am J Drug Alcohol Abuse. 2023 May 4;49(3):345-358. doi: 10.1080/00952990.2022.2128361. Epub 2022 Nov 8.
Hippocampal and cerebellar neuropathology occurs in individuals with alcohol use disorders (AUD), resulting in impaired cognitive and motor function. Evaluate the effects of ethanol on the expression of pro- and anti-inflammatory molecules, as well as the effects of the anti-inflammatory PPAR-γ agonist pioglitazone in suppressing ethanol-induced neuroinflammation. Adult male and female mice were treated chronically with ethanol for just under a month followed by a single acute binge dose of ethanol. Animals were provided liquid diet in the absence of ethanol (Control; n = 18, 9 M/9F), liquid diet containing ethanol (ethanol; n = 22, 11 M/11F), or liquid diet containing ethanol plus gavage administration of 30.0 mg/kg pioglitazone (ethanol + pioglitazone; n = 20, 10 M/10F). The hippocampus and cerebellum were isolated 24 h following the binge dose of ethanol, mRNA was isolated, and pro- and anti-inflammatory molecules were quantified by qRT-PCR. Ethanol significantly (p < .05) increased the expression of pro-inflammatory molecules IL-1β, TNF-α, CCL2, and COX2; increased the expression of inflammasome-related molecules NLRP3 and Casp1 but decreased IL-18; and altered the expression of anti-inflammatory molecules including TGFβR1 in the hippocampus and cerebellum, though some differences were observed between males and females and the two brain regions. The anti-inflammatory pioglitazone inhibited ethanol-induced alterations in the expression of most, but not all, inflammation-related molecules. Chronic plus binge administration of ethanol induced the expression of inflammatory molecules in adult mice and pioglitazone suppressed ethanol-induced neuroinflammation.
海马和小脑神经病理学发生在患有酒精使用障碍 (AUD) 的个体中，导致认知和运动功能受损。评估乙醇对前炎症和抗炎分子表达的影响，以及抗炎 PPAR-γ 激动剂吡格列酮抑制乙醇诱导的神经炎症的作用。成年雄性和雌性小鼠接受近一个月的慢性乙醇处理，随后给予单次急性乙醇 binge 剂量。动物接受不含乙醇的液体饮食（对照；n = 18，9 只雄性/9 只雌性）、含乙醇的液体饮食（乙醇；n = 22，11 只雄性/11 只雌性）或含乙醇和灌胃给予 30.0 mg/kg 吡格列酮的液体饮食（乙醇+吡格列酮；n = 20，10 只雄性/10 只雌性）。在乙醇 binge 剂量后 24 小时分离海马和小脑，分离 mRNA，并通过 qRT-PCR 定量前炎症和抗炎分子。乙醇显著（p <.05）增加了促炎分子 IL-1β、TNF-α、CCL2 和 COX2 的表达；增加了炎症小体相关分子 NLRP3 和 Casp1 的表达，但降低了 IL-18 的表达；并改变了海马和小脑中抗炎分子的表达，包括 TGFβR1，但在雄性和雌性以及两个脑区之间观察到一些差异。抗炎吡格列酮抑制了乙醇诱导的大多数炎症相关分子的表达改变，但不是全部。慢性加 binge 给予乙醇诱导成年小鼠炎症分子的表达，吡格列酮抑制乙醇诱导的神经炎症。
