Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, USA.
Department of Physiology, Southern Illinois University School of Medicine, Carbondale, IL, USA; Department of Anatomy, Southern Illinois University School of Medicine, Carbondale, IL, USA; Center for Integrated Research in the Cognitive and Neural Sciences, Southern Illinois University School of Medicine, Carbondale, IL, USA.
Neurobiol Aging. 2021 Jun;102:188-199. doi: 10.1016/j.neurobiolaging.2021.02.015. Epub 2021 Feb 26.
An age-related decrease in hippocampal metabolism correlates with cognitive decline. Hippocampus-dependent learning and memory requires glutamatergic neurotransmission supported by glutamate-glutamine (GLU-GLN) cycling between neurons and astrocytes. We examined whether GLU-GLN cycling in hippocampal subregions (dentate gyrus and CA1) in Fischer 344 rats was altered with age and cognitive status. Hippocampal slices from young adult, aged cognitively-unimpaired (AU) and aged cognitively-impaired (AI) rats were incubated in artificial cerebrospinal fluid (aCSF) containing 1-C-glucose to assess neural metabolism. Incorporation of C-glucose into glutamate and glutamine, measured by mass spectroscopy/liquid chromatography tandem mass spectroscopy, did not significantly differ between groups. However, when C-acetate, a preferential astrocytic metabolite, was used, a significant increase in C-labeled glutamate was observed in slices from AU rats. Taken together, the data suggest that resting state neural metabolism and GLU-GLN cycling may be preserved during aging when sufficient extracellular glucose is available, but that enhanced astroglial metabolism can occur under resting state conditions. This may be an aging-related compensatory change to maintain hippocampus-dependent cognitive function.
随着年龄的增长，海马体代谢能力下降与认知能力下降有关。海马体依赖的学习和记忆需要谷氨酸能神经传递，这需要神经元和星形胶质细胞之间的谷氨酸-谷氨酰胺(GLU-GLN)循环来支持。我们研究了费希尔 344 大鼠海马体亚区（齿状回和 CA1）的 GLU-GLN 循环是否随年龄和认知状态而改变。从小鼠海马体中分离出海马体切片，将其置于含有 1-C-葡萄糖的人工脑脊液(aCSF)中孵育，以评估神经代谢情况。通过质谱/液相色谱串联质谱测量，C-葡萄糖掺入谷氨酸和谷氨酰胺的情况在各组之间没有显著差异。然而，当使用 C-醋酸盐（一种优先的星形胶质细胞代谢物）时，从 AU 大鼠的切片中观察到 C 标记的谷氨酸显著增加。总的来说，这些数据表明，当有足够的细胞外葡萄糖时，静息状态下的神经代谢和 GLU-GLN 循环可能在衰老过程中得到维持，但在静息状态下可能会发生增强的星形胶质细胞代谢。这可能是一种与衰老相关的代偿性变化，以维持海马体依赖的认知功能。
