Brain glycogen re‐awakened

Abstract

The mammalian brain contains glycogen, which is located predominantly in astrocytes, but its function is unclear. A principal role for brain glycogen as an energy reserve, analogous to its role in the periphery, had been universally dismissed based on its relatively low concentration, an assumption apparently reinforced by the limited duration that the brain can function in the absence of glucose. However, during insulin-induced hypoglycaemia, where brain glucose availability is limited, glycogen content falls first in areas with the highest metabolic rate, suggesting that glycogen provides fuel to support brain function during pathological hypoglycaemia. General anaesthesia results in elevated brain glycogen suggesting quiescent neurones allow glycogen accumulation, and as long ago as the 1950s it was shown that brain glycogen accumulates during sleep, is mobilized upon waking, and that sleep deprivation results in region-specific decreases in brain glycogen, implying a supportive functional role for brain glycogen in the conscious, awake brain. Interest in brain glycogen has recently been re-awakened by the first continuous in vivo measurements using NMR spectroscopy, by the general acceptance of metabolic coupling between glia and neurones involving intercellular transfer of energy substrate, and by studies supporting a prominent physiological role for brain glycogen as a provider of supplemental energy substrate during periods of increased tissue energy demand, when ambient normoglycaemic glucose is unable to meet immediate energy requirements.

Quantification of Metabolic Rearrangements During Neural Stem Cells Differentiation into Astrocytes by Metabolic Flux Analysis

“…Importantly, glutamatergic and GABAergic neurotransmission processes are dependent on astrocytic metabolism for neurotransmitter replenishment [4]. Furthermore, astrocytes store brain energy currency in the form of glycogen [7], and release substrates for neuronal oxidative phosphorylation [25]. Moreover, astrocytes have been suggested as contributors to neurodegenerative disorders by various mechanisms, including via metabolic dysfunction [27], making them potential targets for novel strategies to treat brain disorders.…”

Glycogen metabolism in tissues from a mouse model of Lafora disease

“…5). We did not analyze brain glycogen because it is very difficult to preserve post-mortem without specialized strategies, such as in situ microwaving [35]. The negative results with enzyme activity measurements are difficult to interpret since most brain glycogen is present in the glial cells and not the neurons [35].…”

Relationship between motor corticospinal excitability and ventilatory response during intense exercise

“…Hypoglycaemia induced during prolonged exercise has been shown to cause a decrease in glycogen levels in various brain regions including the motor cortex (Matsui et al 2011). Brain glycogen is known to localize in astrocytes and to be utilized as an important energy source for neurons (Brown 2004). Oz et al (2009) showed by using 13C NMR that brain glycogen supports energy metabolism when glucose supply from the blood is inadequate in humans.…”