Trinity College Institute for Neuroscience, Dublin, Ireland.
Neurobiol Aging. 2011 Dec;32(12):2318.e1-15. doi: 10.1016/j.neurobiolaging.2010.04.001. Epub 2010 Jun 8.
Age is characterized by deficits in synaptic function identified by decreased performance of aged animals in spatial learning tasks and reduced ability of animals to sustain long term potentiation (LTP). Several cellular and molecular events are correlated with these deficits, many of which are indicative of age-related neuroinflammatory and oxidative cell stress. It is significant that agents which decrease microglial activation are commonly associated with restoration of function. We set out to examine whether the n-3 polyunsaturated fatty acid docosapentaenoic acid (DPA), which is a metabolite of eicosapentaenoic acid (EPA), could modulate the age-related increase in microglial activation and the associated increase in oxidative changes and therefore impact on synaptic function in aged rats. We demonstrate that docosapentaenoic acid possesses neurorestorative effects and is capable of downregulating microglial activation. The data show that it also decreases the coupled activation of sphingomyelinase and caspase 3, probably because of its ability to decrease age-related oxidative changes, and consequently attenuates the age-related decrease in spatial learning and long-term potentiation.
年龄的特征是突触功能的缺陷，这表现在老年动物在空间学习任务中的表现下降，以及它们维持长时程增强（LTP）的能力降低。许多与这些缺陷相关的细胞和分子事件表明，与年龄相关的神经炎症和氧化细胞应激有关。重要的是，降低小胶质细胞激活的药物通常与功能的恢复有关。我们着手研究二十二碳五烯酸（DPA），一种二十碳五烯酸（EPA）的代谢物，是否可以调节与年龄相关的小胶质细胞激活增加，以及与之相关的氧化变化增加，从而影响老年大鼠的突触功能。我们证明二十二碳五烯酸具有神经修复作用，能够下调小胶质细胞的激活。这些数据表明，它还可以降低鞘磷脂酶和半胱天冬酶 3 的偶联激活，可能是因为它能够降低与年龄相关的氧化变化，从而减弱与年龄相关的空间学习和长时程增强的下降。
