Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, Brazil.
Exp Gerontol. 2020 Nov;141:111097. doi: 10.1016/j.exger.2020.111097. Epub 2020 Sep 25.
It is well known that patients with Alzheimer's disease (AD) have imbalances in blood thiamine concentrations and lower activity of thiamine-dependent enzymes. Benfotiamine, a more bioavailable thiamine analog, has been proposed as an alternative to counteract these changes related to thiamine metabolism. Thus, our study aimed to analyze the effects of benfotiamine supplementation on brain thiamine absorption, as well as on parameters related to neuronal energy metabolism and disease progression in an experimental model of sporadic AD induced by intracerebroventricular injection of streptozotocin (STZ) in rats. The supplementation with 150 mg/kg of benfotiamine for 30 days increased the concentrations of thiamine diphosphate in the hippocampus and entorhinal cortex. This led to an improvement in mitochondria enzymes and insulin signaling pathway, with inactivation of GSK3α/β and ERK1/2, which are two tau-kinases related to the progression of AD, which could decrease tau hyperphosphorylation and apoptosis signaling. Besides, we observed an increased amount of Glun2b subunit of NMDA receptors, decreased inflammation, and improvement of cognitive deficit. Together, these results suggest that benfotiamine could be a potential therapeutic approach in the treatment of sporadic AD.
众所周知，阿尔茨海默病（AD）患者的血液硫胺素浓度失衡，硫胺素依赖性酶活性降低。苯磷硫胺，一种更具生物利用度的硫胺素类似物，已被提议作为对抗这些与硫胺素代谢相关变化的替代物。因此，我们的研究旨在分析苯磷硫胺补充对脑内硫胺素吸收的影响，以及对通过向大鼠侧脑室注射链脲佐菌素（STZ）诱导的散发性 AD 实验模型中神经元能量代谢和疾病进展相关参数的影响。30 天内每天补充 150mg/kg 的苯磷硫胺可增加海马体和内嗅皮层中硫胺素二磷酸的浓度。这导致线粒体酶和胰岛素信号通路得到改善，同时使与 AD 进展相关的两种 tau 激酶 GSK3α/β 和 ERK1/2 失活，从而减少 tau 过度磷酸化和细胞凋亡信号。此外，我们观察到 NMDA 受体的 Glun2b 亚基数量增加，炎症减少，认知缺陷得到改善。总之，这些结果表明苯磷硫胺可能是治疗散发性 AD 的一种潜在治疗方法。
