Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo 05508-900, Brazil.
Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, São Paulo 05508-900, Brazil.
Neuroscience. 2021 Jun 15;465:142-153. doi: 10.1016/j.neuroscience.2021.04.022. Epub 2021 May 3.
Among different kinds of dietary energy restriction, intermittent fasting (IF) has been considered a dietary regimen which causes a mild stress to the organism. IF can stimulate proteins and signaling pathways related to cell stress that can culminate in the increase of the body resistance to severe stress conditions. Energy intake reduction induced by IF can induce modulation of receptors, kinases, and phosphatases, which in turn can modulate the activation of transcription factors such as NF-E2-related factor 2 (NRF2) and cAMP response element-binding (CREB) which regulate the transcription of genes related to the translation of proteins such as growth factors: brain-derived neurotrophic factor (BDNF), chaperone proteins: heat shock proteins (HSP), and so on. It has been shown that toll-like receptors (TLRs) are important molecules in innate immune response which are present not only in the periphery but also in neurons and glial cells. In central nervous system, TLRs can exert functions related to set up responses to infection, as well as influence neural progenitor cell proliferation and differentiation, being involved in cognitive parameters such as learning and memory. Little is known about the involvement of TLR4 on the beneficial effects induced by IF protocol. The present work investigated the effects of IF on memory and on the signaling mechanisms associated with NRF2 and CREB in Tlr4 knockout mice. The results suggest that TLR4 participates in the modulatory effects of IF on oxidative stress levels, on the transcription factors CREB and NRF2, and on BDNF and HSP90 expressions in hippocampus.
在不同类型的饮食能量限制中，间歇性禁食（IF）被认为是一种对机体造成轻度应激的饮食方案。IF 可以刺激与细胞应激相关的蛋白质和信号通路，最终导致机体对严重应激条件的抵抗力增强。IF 引起的能量摄入减少可以诱导受体、激酶和磷酸酶的调节，进而可以调节转录因子如核因子-红细胞 2 相关因子 2（NRF2）和 cAMP 反应元件结合（CREB）的激活，这些转录因子调节与蛋白质翻译相关的基因的转录，如生长因子：脑源性神经营养因子（BDNF）、伴侣蛋白：热休克蛋白（HSP）等。已经表明， toll 样受体（TLRs）是先天免疫反应中的重要分子，不仅存在于外周，也存在于神经元和神经胶质细胞中。在中枢神经系统中，TLRs 可以发挥与感染反应相关的功能，以及影响神经祖细胞的增殖和分化，参与学习和记忆等认知参数。关于 TLR4 参与 IF 方案诱导的有益作用的了解甚少。本研究探讨了 IF 对记忆的影响以及对 Tlr4 敲除小鼠海马中与 NRF2 和 CREB 相关的信号机制的影响。结果表明，TLR4 参与了 IF 对氧化应激水平、转录因子 CREB 和 NRF2 以及 BDNF 和 HSP90 表达的调节作用。
