Quiroz-Baez Ricardo, Arias Clorinda
Secretaría de Salud, Institutos Nacionales de Salud, Instituto Nacional de Geriatría, Dirección de Investigación, Departamento de Investigación Básica. Ciudad de México, México
Rev Med Inst Mex Seguro Soc. 2018;56(Suppl 1):S18-S25.
Recent evidence suggests that early neurodegenerative events associated with Alzheimer’s disease (AD) probably begin in the synaptic terminal, where it has been reported a large accumulation of β-amyloid protein (Aβ), one of the main factors described in the development of AD. We analyzed the influence of energy metabolism on the toxic effects of Aβ during aging on synaptosomes from neocortex and hippocampus of rats exposed to inhibitors of glycolytic and mitochondrial metabolism and we evaluated the protective effects of some antioxidant compounds.
Synaptosomes were obtained by differential centrifugation in sucrose gradients and their redox activity was determined with the MTT assay.
The mitochondrial activity of synaptosomes from young rats was not altered by the presence of Aβ; the ones obtained from old rats showed an increase in susceptibility to Aβ; this activity was greater in the synaptic terminals of the hippocampus.
These results provide experimental support for the hypothesis that certain risk factors, such as energy metabolism dysfunction or the aging process itself, may increase vulnerability to Aβ. Hippocampal region is more susceptible to Aβ and its effect increases with age in relation to the neocortex, which would agree with the damage gradient reported in the AD.
最近的证据表明，与阿尔茨海默病（AD）相关的早期神经退行性事件可能始于突触终末，据报道，在突触终末大量积聚β-淀粉样蛋白（Aβ），这是AD发病过程中描述的主要因素之一。我们分析了能量代谢对衰老过程中Aβ对暴露于糖酵解和线粒体代谢抑制剂的大鼠新皮质和海马突触体毒性作用的影响，并评估了一些抗氧化化合物的保护作用。
通过在蔗糖梯度中进行差速离心获得突触体，并用MTT法测定其氧化还原活性。
年轻大鼠突触体的线粒体活性不受Aβ存在的影响；老年大鼠的突触体对Aβ的敏感性增加；这种活性在海马的突触终末更高。
这些结果为以下假设提供了实验支持，即某些风险因素，如能量代谢功能障碍或衰老过程本身，可能会增加对Aβ的易感性。海马区对Aβ更敏感，并且相对于新皮质，其作用随年龄增长而增加，这与AD中报道的损伤梯度一致。
