Molinari Claudio, Morsanuto Vera, Ruga Sara, Notte Felice, Farghali Mahitab, Galla Rebecca, Uberti Francesca
Laboratory of Physiology, Department of Translational Medicine, University of Piemonte Orientale, Via Solaroli 17, 28100 Novara, Italy.
Brain Sci. 2020 May 9;10(5):285. doi: 10.3390/brainsci10050285.
An important link between brain aging and a class of growth/survival factors called neurotrophins has recently been demonstrated. In particular, brain-derived neurotrophic factor (BDNF) plays a fundamental role during age-related synaptic loss, preventing cerebral atrophy and cognitive decline. The aim of the present study was to investigate whether the use of low dose BDNF sequentially kinetic activated (SKA) was able to counteract some mechanisms underlying the degeneration and aging of nervous tissue by increasing endogenous protection mechanisms. Both in vitro and in vivo experiments were performed to assess the ability of BDNF SKA to protect and regenerate survival-related molecular pathways, studying intestinal absorption in vitro and brain function in vivo. Our pioneering results show that BDNF SKA is able to induce the endogenous production of BDNF, using its receptor TrkB and influencing the apolipoprotein E expression. Moreover, BDNF SKA exerted effects on β-Amyloid and Sirtuin 1 proteins, confirming the hypothesis of a fine endogenous regulatory effect exerted by BDNF SKA in maintaining the health of both neurons and astrocytes. For this reason, a change in BDNF turnover is considered as a positive factor against brain aging.
最近已证实大脑衰老与一类称为神经营养因子的生长/存活因子之间存在重要联系。特别是,脑源性神经营养因子(BDNF)在与年龄相关的突触丧失过程中发挥着重要作用,可防止脑萎缩和认知衰退。本研究的目的是调查使用低剂量的顺序动力学激活(SKA)BDNF是否能够通过增加内源性保护机制来对抗神经组织退化和衰老的一些潜在机制。进行了体外和体内实验,以评估BDNF SKA保护和再生与存活相关分子途径的能力,在体外研究肠道吸收,在体内研究脑功能。我们的开创性结果表明,BDNF SKA能够利用其受体TrkB诱导BDNF的内源性产生,并影响载脂蛋白E的表达。此外,BDNF SKA对β-淀粉样蛋白和沉默调节蛋白1发挥作用,证实了BDNF SKA在维持神经元和星形胶质细胞健康方面发挥精细内源性调节作用的假设。因此,BDNF周转的变化被认为是对抗大脑衰老的积极因素。