Tapia-Arancibia Lucia, Aliaga Esteban, Silhol Michelle, Arancibia Sandor
Inserm, U710, Montpellier, F-34095 France.
Brain Res Rev. 2008 Nov;59(1):201-20. doi: 10.1016/j.brainresrev.2008.07.007. Epub 2008 Aug 3.
The decline observed during aging involves multiple factors that influence several systems. It is the case for learning and memory processes which are severely reduced with aging. It is admitted that these cognitive effects result from impaired neuronal plasticity, which is altered in normal aging but mainly in Alzheimer disease. Neurotrophins and their receptors, notably BDNF, are expressed in brain areas exhibiting a high degree of plasticity (i.e. the hippocampus, cerebral cortex) and are considered as genuine molecular mediators of functional and morphological synaptic plasticity. Modification of BDNF and/or the expression of its receptors (TrkB.FL, TrkB.T1 and TrkB.T2) have been described during normal aging and Alzheimer disease. Interestingly, recent findings show that some physiologic or pathologic age-associated changes in the central nervous system could be offset by administration of exogenous BDNF and/or by stimulating its receptor expression. These molecules may thus represent a physiological reserve which could determine physiological or pathological aging. These data suggest that boosting the expression or activity of these endogenous protective systems may be a promising therapeutic alternative to enhance healthy aging.
衰老过程中观察到的衰退涉及多个影响多个系统的因素。学习和记忆过程就是如此，随着衰老，这些过程会严重衰退。人们认为，这些认知效应是由神经元可塑性受损导致的，在正常衰老过程中神经元可塑性会发生改变，但在阿尔茨海默病中改变更为明显。神经营养因子及其受体，尤其是脑源性神经营因子（BDNF），在具有高度可塑性的脑区（即海马体、大脑皮层）中表达，被认为是功能和形态突触可塑性的真正分子介质。在正常衰老和阿尔茨海默病过程中，BDNF及其受体（TrkB.FL、TrkB.T1和TrkB.T2）的表达都有改变。有趣的是，最近的研究结果表明，中枢神经系统中一些与年龄相关的生理或病理变化可以通过给予外源性BDNF和/或刺激其受体表达来抵消。因此，这些分子可能代表一种生理储备，它可以决定生理或病理衰老。这些数据表明，提高这些内源性保护系统的表达或活性可能是促进健康衰老的一种有前景的治疗选择。
