Thiamine is essential for normal brain function and its deficiency causes metabolic impairment, specific lesions, oxidative damage and reduced adult hippocampal neurogenesis (AHN). Thiamine precursors with increased bioavailability, especially benfotiamine, exert neuroprotective effects not only for thiamine deficiency (TD), but also in mouse models of neurodegeneration. As it is known that AHN is impaired by stress in rodents, we exposed C57BL6/J mice to predator stress for 5 consecutive nights and studied the proliferation (number of Ki67-positive cells) and survival (number of BrdU-positive cells) of newborn immature neurons in the subgranular zone of the dentate gyrus. In stressed mice, the number of Ki67- and BrdU-positive cells was reduced compared to non-stressed animals. This reduction was prevented when the mice were treated (200mg/kg/day in drinking water for 20days) with thiamine or benfotiamine, that were recently found to prevent stress-induced behavioral changes and glycogen synthase kinase-3β (GSK-3β) upregulation in the CNS. Moreover, we show that thiamine and benfotiamine counteract stress-induced bodyweight loss and suppress stress-induced anxiety-like behavior. Both treatments induced a modest increase in the brain content of free thiamine while the level of thiamine diphosphate (ThDP) remained unchanged, suggesting that the beneficial effects observed are not linked to the role of this coenzyme in energy metabolism. Predator stress increased hippocampal protein carbonylation, an indicator of oxidative stress. This effect was antagonized by both thiamine and benfotiamine. Moreover, using cultured mouse neuroblastoma cells, we show that in particular benfotiamine protects against paraquat-induced oxidative stress. We therefore hypothesize that thiamine compounds may act by boosting anti-oxidant cellular defenses, by a mechanism that still remains to be unveiled. Our study demonstrates, for the first time, that thiamine and benfotiamine prevent stress-induced inhibition of hippocampal neurogenesis and accompanying physiological changes. The present data suggest that thiamine precursors with high bioavailability might be useful as a complementary therapy in several neuropsychiatric disorders.

中文翻译：

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硫胺素和苯丙胺类固醇可防止应激对捕食小鼠的海马神经发生抑制，而不会影响脑中硫胺素二磷酸水平。

硫胺素对于正常的脑功能至关重要，其缺乏会导致代谢受损，特定病变，氧化损伤并减少成年海马神经发生（AHN）。具有更高生物利用度的硫胺素前体，尤其是苯丁胺，不仅对硫胺素缺乏症（TD）有神经保护作用，而且在神经退行性小鼠模型中也具有神经保护作用。众所周知，啮齿动物的应激会损害AHN，我们将C57BL6 / J小鼠连续5天暴露于捕食者应激下，研究了新生小鼠的增殖（Ki67阳性细胞数）和存活（BrdU阳性细胞数）齿状回亚颗粒区的未成熟神经元。与非应激动物相比，在应激小鼠中，Ki67和BrdU阳性细胞数量减少。当用硫胺素或苯乙胺明对小鼠进行处理（200mg / kg /天，在饮用水中持续20天）时，这种减少被阻止，硫胺素或苯甲酸是最近被发现可以预防应激诱导的行为改变和糖原合酶激酶-3β（GSK-3β）的上调。 CNS。此外，我们表明，硫胺素和苯丙胺能抵消压力引起的体重减轻并抑制压力引起的焦虑样行为。两种治疗均引起大脑中游离硫胺素的适度增加，而硫胺素二磷酸（ThDP）的水平保持不变，这表明观察到的有益作用与该辅酶在能量代谢中的作用无关。捕食者应激会增加海马蛋白的羰基化，这是氧化应激的指标。硫胺素和苯乙胺明均拮抗这一作用。而且，使用培养的小鼠神经母细胞瘤细胞，我们显示出特别是苯丁胺能保护百草枯引起的氧化应激。因此，我们推测，硫胺素化合物可能通过增强抗氧化细胞防御作用而发挥作用，其机制仍有待揭示。我们的研究首次证明，硫胺素和苯丙胺能阻止应激诱导的海马神经发生抑制以及随之而来的生理变化。目前的数据表明，具有高生物利用度的硫胺素前体可能在几种神经精神疾病中可用作补充疗法。仍然有待揭示的机制。我们的研究首次证明，硫胺素和苯丙胺能阻止应激诱导的海马神经发生抑制以及随之而来的生理变化。目前的数据表明，具有高生物利用度的硫胺素前体可能在几种神经精神疾病中可用作补充疗法。仍然有待揭示的机制。我们的研究首次证明，硫胺素和苯丙胺能阻止应激诱导的海马神经发生抑制以及随之而来的生理变化。目前的数据表明，具有高生物利用度的硫胺素前体可能在几种神经精神疾病中可用作补充疗法。