The effect of aging on the spatial distribution of glycogen in layer I of the somatosensory cortex in mice

Abstract

Astrocytes are the most abundant type of glial cell in the brain, required to ensure optimal neuronal functioning, neurogenesis, and brain vascular tone. Moreover, they play a crucial role in support of neuronal metabolism. The human brain utilizes around 20% of the energy consumed to ensure its proper function. Glucose, an important energy source for the brain, access the neuropil across the blood-brain barrier (BBB), and then is transported into astrocytes through their perivascular end-feet, where it can be stored as glycogen. Furthermore, lactate can be synthesized through glycogenolysis and then shuttled via monocarboxylate transporters (MCTs) to neurons to fuel their tricarboxylic acid (TCA) cycle. This mechanism is known as astrocyte-neuron lactate shuttle (ANLS) and is involved in learning and memory formation. Aging is associated with a decline of faculties such as memory, motor skills, and sensory perception. These deficits are not thought to be due to a substantial loss of neurons but rather changes at the level of connectivity, morphological changes, and white matter structure. In the present study, we aim to compare the glycogen distribution in layer I of the somatosensory cortex between adult (4 months old) and geriatric mice (24 months old). We carried out the visual analysis using Connectome Explorer, which allows us to explore, in real-time, brain reconstructions at the nanometric-level. Using the computational tool GLAM (Glycogen-derived Lactate Absorption Map), we can infer a probability map of the locations where astrocytic glycogen-derived lactate is most likely accessing the surrounding neurites. We analyzed and compared the probability maps on axons, dendrites, boutons, and spines to make a functional hypothesis about single compartments’ energy consumption. Our results indicate that aging brains have a more glycolytic metabolism, with fewer peaks facing mitochondria, and smaller glycogen granules.