Aging ‐associated changes in hippocampal glycogen metabolism in mice. Evidence for and against astrocyte‐to‐neuron lactate shuttle

Abstract Lactate derived from astrocytic glycogen has been shown to support memory formation in hippocampi of young animals, inhibiting it in old animals. Here we show, using quantitative mass spectrometry‐based proteomics, immunofluorescence, and qPCR that aging is associated with an increase of glycogen metabolism enzymes concentration and shift in their localization from astrocytes to neurons. These changes are accompanied with reorganization of hippocampal energy metabolism which is manifested by elevated capacity of aging neurons to oxidize glucose in glycolysis and mitochondria, and decreased ability for fatty acids utilization. Our observations suggest that astrocyte‐to‐neuron lactate shuttle may operate in young hippocampi, however, during aging neurons become independent on astrocytic lactate and the metabolic crosstalk between the brain's cells is disrupted. Main Points With age astrocyte‐neuron metabolic crosstalk becomes disrupted. Memory formation becomes independent on astrocyte‐neuron lactate shuttle. Memory deficits in young and old animals have different metabolic basis and thus, require different treatment.
Source: Glia - Category: Neurology Authors: Tags: RESEARCH ARTICLE Source Type: research