Center for Behavioral Teratology, San Diego State University, San Diego, CA 92120, USA.
Department of Cellular and Physiological Sciences, Faculty of Medicine, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.
Cells. 2023 Feb 8;12(4):546. doi: 10.3390/cells12040546.
Alcohol (ethanol) exposure during pregnancy can adversely affect development, with long-lasting consequences that include neuroimmune, cognitive, and behavioral dysfunction. Alcohol-induced alterations in cytokine levels in the hippocampus may contribute to abnormal cognitive and behavioral outcomes in individuals with fetal alcohol spectrum disorders (FASD). Nutritional intervention with the essential nutrient choline can improve hippocampal-dependent behavioral impairments and may also influence neuroimmune function. Thus, we examined the effects of choline supplementation on hippocampal cytokine levels in adolescent and adult rats exposed to alcohol early in development. From postnatal day (PD) 4-9 (third trimester-equivalent), Sprague-Dawley rat pups received ethanol (5.25 g/kg/day) or sham intubations and were treated with choline chloride (100 mg/kg/day) or saline from PD 10-30; hippocampi were collected at PD 35 or PD 60. Age-specific ethanol-induced increases in interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), and keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO) were identified in adulthood, but not adolescence, whereas persistent ethanol-induced increases of interleukin-6 (IL-6) levels were present at both ages. Interestingly, choline supplementation reduced age-related changes in interleukin-1 beta (IL-1β) and interleukin-5 (IL-5) as well as mitigating the long-lasting increase in IFN-γ in ethanol-exposed adults. Moreover, choline influenced inflammatory tone by modulating ratios of pro- to -anti-inflammatory cytokines. These results suggest that ethanol-induced changes in hippocampal cytokine levels are more evident during adulthood than adolescence, and that choline can mitigate some effects of ethanol exposure on long-lasting inflammatory tone.
怀孕期间暴露于酒精会对发育产生不利影响，导致长期的神经免疫、认知和行为功能障碍。酒精引起的海马细胞因子水平的改变可能导致胎儿酒精谱系障碍（FASD）个体的异常认知和行为结果。必需营养素胆碱的营养干预可以改善海马依赖性行为障碍，也可能影响神经免疫功能。因此，我们研究了胆碱补充对发育期早期暴露于酒精的青春期和成年大鼠海马细胞因子水平的影响。从出生后第 4-9 天（相当于第三个 trimester）开始，Sprague-Dawley 幼鼠接受乙醇（5.25 g/kg/天）或假灌胃，并从第 10-30 天开始给予氯化胆碱（100 mg/kg/天）或生理盐水；在第 35 天或第 60 天收集海马。在成年期而非青春期，发现特定于年龄的乙醇诱导的干扰素 γ（IFN-γ）、肿瘤坏死因子 α（TNF-α）和角质细胞化学引诱物/人生长调节致癌基因（KC/GRO）增加，但在两个年龄阶段均存在持续性的乙醇诱导的白细胞介素-6（IL-6）水平升高。有趣的是，胆碱补充减少了与年龄相关的白细胞介素-1β（IL-1β）和白细胞介素-5（IL-5）的变化，并减轻了乙醇暴露的成年大鼠中干扰素-γ的长期增加。此外，胆碱通过调节促炎细胞因子与抗炎细胞因子的比例来影响炎症状态。这些结果表明，与青春期相比，乙醇引起的海马细胞因子水平的变化在成年期更为明显，并且胆碱可以减轻乙醇暴露对长期炎症状态的一些影响。
