Behavioral Neuroscience Program (PTN, LCV, TD, LMS), Department of Psychology, Binghamton University, State University of New York, Binghamton, New York.
Alcohol Clin Exp Res. 2019 Mar;43(3):425-438. doi: 10.1111/acer.13946. Epub 2019 Jan 20.
Alcohol-related brain damage (ARBD) is associated with neurotoxic effects of heavy alcohol use and nutritional deficiency, in particular thiamine deficiency (TD), both of which induce inflammatory responses in brain. Although neuroinflammation is a critical factor in the induction of ARBD, few studies have addressed the specific contribution(s) of ethanol (EtOH) versus TD.
Adult rats were randomly divided into 6 conditions: chronic EtOH treatment (CET) where rats consumed a 20% v/v solution of EtOH for 6 months; CET with injections of thiamine (CET + T); severe pyrithiamine-induced TD (PTD); moderate PTD; moderate PTD during CET; and pair-fed controls. After the treatments, the rats were split into 3 recovery phase time points: the last day of treatment (time point 1), acute recovery (time point 2: 24 hours posttreatment), and delayed recovery (time point 3: 3 weeks posttreatment). At these time points, vulnerable brain regions (thalamus, hippocampus, frontal cortex) were collected and changes in neuroimmune markers were assessed using a combination of reverse transcription polymerase chain reaction and protein analysis.
CET led to minor fluctuations in neuroimmune genes, regardless of the structure being examined. In contrast, PTD treatment led to a profound increase in neuroimmune genes and proteins within the thalamus. Cytokine changes in the thalamus ranged in magnitude from moderate (3-fold and 4-fold increase in interleukin-1β [IL-1β] and IκBα) to severe (8-fold and 26-fold increase in tumor necrosis factor-α and IL-6, respectively). Though a similar pattern was observed in the hippocampus and frontal cortex, overall fold increases were moderate relative to the thalamus. Importantly, neuroimmune gene induction varied significantly as a function of severity of TD, and most genes displayed a gradual recovery across time.
These data suggest an overt brain inflammatory response by TD and a subtle change by CET alone. Also, the prominent role of TD in the immune-related signaling pathways leads to unique regional and temporal profiles of induction of neuroimmune genes.
酒精相关性脑损伤（ARBD）与酒精使用的神经毒性作用和营养缺乏有关，特别是硫胺素缺乏症（TD），两者都会在大脑中引发炎症反应。尽管神经炎症是诱导 ARBD 的一个关键因素，但很少有研究涉及乙醇（EtOH）与 TD 的具体贡献。
成年大鼠被随机分为 6 种情况：慢性 EtOH 处理（CET），大鼠饮用 20% v/v 的 EtOH 溶液 6 个月；CET 加硫胺素注射（CET+T）；严重吡哆醛诱导的 TD（PTD）；中度 PTD；CET 期间的中度 PTD；以及配对喂养对照。在治疗后，大鼠被分为 3 个恢复阶段时间点：治疗的最后一天（时间点 1）、急性恢复（时间点 2：治疗后 24 小时）和延迟恢复（时间点 3：治疗后 3 周）。在这些时间点，采集易损脑区（丘脑、海马体、额叶皮层），并通过逆转录聚合酶链反应和蛋白质分析结合评估神经免疫标志物的变化。
CET 导致神经免疫基因的轻微波动，无论检查的结构如何。相比之下，PTD 治疗导致丘脑内神经免疫基因和蛋白质的显著增加。丘脑内细胞因子的变化幅度从中等（白细胞介素-1β[IL-1β]和 IκBα增加 3 倍和 4 倍）到严重（肿瘤坏死因子-α和 IL-6 分别增加 8 倍和 26 倍）不等。虽然在海马体和额叶皮层中观察到类似的模式，但相对于丘脑，总体倍数增加是中等的。重要的是，神经免疫基因的诱导因 TD 的严重程度而显著变化，大多数基因随时间逐渐恢复。
这些数据表明 TD 引起明显的大脑炎症反应，而 CET 单独引起轻微变化。此外，TD 在免疫相关信号通路中的突出作用导致了神经免疫基因诱导的独特的区域和时间分布。
