Altered hippocampal astroglial metabolism is associated with aging and preserved spatial learning and memory

An age-related decrease in hippocampal metabolism correlates with cognitive decline. Hippocampusdependent learning and memory requires glutamatergic neurotransmission supported by glutamateglutamine (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 13 C-glucose to assess neural metabolism. Incorporation of 13 C-glucose into glutamate and glutamine, measured by mass spectroscopy/liquid chromatography tandem mass spectroscopy, did not significantly differ between groups. However, when 13 C-acetate, a preferential astrocytic metabolite, was used, a significant increase in 13 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. (c) 2021 Elsevier Inc. All rights reserved.

Automated summary

The age-related decrease in hippocampal metabolism is correlated with cognitive decline. However, the resting state neural metabolism and GLU-GLN cycling may be preserved during aging. Enhanced astroglial metabolism observed in aged cognitively-unimpaired rats may serve as a compensatory change to maintain hippocampus-dependent cognitive function.