Thiamine deficiency (TD) produces severe neurodegenerative lesions. Studies have suggested that primary neurodegenerative events are associated with both oxidative stress and inflammation. Very little is known about the downstream effects on intracellular signaling pathways involved in neuronal death. The primary aim of this work was to evaluate the modulation of p38MAPK and the expression of heme oxygenase 1 (HO-1) in the central nervous system (CNS). Behavioral, metabolic, and morphological parameters were assessed. Mice were separated into six groups: control (Cont), TD with pyrithiamine (Ptd), TD with pyrithiamine and Trolox (Ptd + Tr), TD with pyrithiamine and dimethyl sulfoxide (Ptd + Dmso), Trolox (Tr) and DMSO (Dmso) control groups and treated for 9 days. Control groups received standard feed (AIN-93M), while TD groups received thiamine deficient feed (AIN-93DT). All the groups were subjected to behavioral tests, and CNS samples were collected for cell viability, histopathology and western blot analyses. The Ptd group showed a reduction in weight gain and feed intake, as well as a reduction in locomotor, grooming, and motor coordination activities. Also, Ptd group showed a robust increase in p38MAPK phosphorylation and mild HO-1 expression in the cerebral cortex and thalamus. The Ptd group showed a decreased cell viability, hemorrhage, spongiosis, and astrocytic swelling in the thalamus. Groups treated with Trolox and DMSO displayed diminished p38MAPK phosphorylation in both the structures, as well as attenuated thalamic lesions and behavioral activities. These data suggest that p38MAPK and HO-1 are involved in the TD-induced neurodegeneration in vivo, possibly modulated by oxidative stress and neuroinflammation.

中文翻译：

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硫胺素缺乏调节小鼠脑中的p38MAPK和血红素加氧酶-1：与早期组织和行为变化的关联。

硫胺素缺乏症（TD）会导致严重的神经退行性病变。研究表明，原发性神经退行性事件与氧化应激和炎症有关。关于与神经元死亡有关的细胞内信号通路的下游影响知之甚少。这项工作的主要目的是评估中枢神经系统（CNS）中p38MAPK的调节和血红素加氧酶1（HO-1）的表达。评估行为，代谢和形态参数。将小鼠分为六组：对照组（Cont），TD配巯乙胺（Ptd），TD配巯乙胺和Trolox（Ptd + Tr），TD配巯乙胺和二甲基亚砜（Ptd + Dmso），Trolox（Tr）和DMSO（Dmso） ）对照组，治疗9天。对照组接受标准饲料（AIN-93M），TD组接受硫胺素缺乏饲料（AIN-93DT）。对所有组进行行为测试，并收集CNS样品用于细胞存活力，组织病理学和蛋白质印迹分析。Ptd组的体重增加和采食量减少，运动，修饰和运动协调活动减少。此外，Ptd组在大脑皮层和丘脑中p38MAPK磷酸化水平显着增加，HO-1轻度表达。Ptd组在丘脑中显示出细胞活力降低，出血，海绵状变性和星形胶质细胞肿胀。用Trolox和DMSO治疗的组在两个结构中均显示p38MAPK磷酸化水平降低，丘脑损伤和行为活动减弱。