Why does the brain (not) have glycogen?

Abstract

In the present paper we formulate the hypothesis that brain glycogen is a critical determinant in the modulation of carbohydrate supply at the cellular level. Specifically, we propose that mobilization of astrocytic glycogen after an increase in AMP levels during enhanced neuronal activity controls the concentration of glucose phosphates in astrocytes. This would result in modulation of glucose phosphorylation by hexokinase and upstream cell glucose uptake. This mechanism would favor glucose channeling to activated neurons, supplementing the already rich neuron-astrocyte metabolic and functional partnership with important implications for the energy compounds used to sustain neuronal activity. The hypothesis is based on recent modeling evidence suggesting that rapid glycogen breakdown can profoundly alter the short-term kinetics of glucose delivery to neurons and astrocytes. It is also based on review of the literature relevant to glycogen metabolism during physiological brain activity, with an emphasis on the metabolic pathways identifying both the origin and the fate of this glucose reserve.

In vivo continuous and simultaneous monitoring of brain energy substrates with a multiplex amperometric enzyme-based biosensor device

“…Following this initial increase, brain glucose levels decreased transiently, although still significantly higher than basal glucose levels (all vs. 1.49 70.05 p o0.05 from t¼62 to t¼90 min). Although brain glucose can be produced in astrocytes by glycogenolysis (Di Nuzzo et al, 2011;Dienel, 2011;Hertz et al, 2013), most of the brain glucose is directly taken up from the circulating blood, facilitated by glucose receptors in the blood-brain barrier (BBB) (Duelli and Kuschinsky, 2001). Our results suggest a fast, but limited uptake of glucose by the brain in response to a sudden large increase in glucose in the blood stream.…”

Does abnormal glycogen structure contribute to increased susceptibility to seizures in epilepsy?

“…PC is also the first enzyme of the gluconeogenic pathway (i.e. the pathway converting pyruvate to glucose), which in the brain is followed by activity of phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase (FBPase) to yield phosphoenolpyruvate and fructose-6-phosphate, respectively (see DiNuzzo et al, 2011 and references therein). Glutamate-induced activation of PEPCK and glycogen synthesis has been first observed in skeletal muscle (Odedra and Palmer, 1981).…”

“…As an illustration, assuming an astrocytic glycogen content of 20 μmol/g (4 μmol/g in whole tissue) a seemingly negligible 5% degradation of glycogen would allow glycogenolysis to keep going for 30 seconds at 10 times the glucose consumption rate of resting human brain astrocytes (~0.2 μmol/g/min). These unique features of glycogenolysis contributed to revise the long-held concept of glycogen as a small emergency depot used exclusively in case of energy failure (for a review, see DiNuzzo et al, 2011). Rather, as it will be clear below glycogen occupies a fundamental position in the maintenance of ion homeostasis in the brain and hence it is a potential target in the pathophysiology of epilepsy.…”

Insulin and Insulin-like Growth Factor 1 (IGF-1) Modulate Cytoplasmic Glucose and Glycogen Levels but Not Glucose Transport across the Membrane in Astrocytes

“…Astrocytes form an intimately connected network with neurons and with endothelial cells, where the end feet form well defined rosette-like structures, adjacent to the vessel wall (2). This acts as a conduit for glucose and other molecules for neuronal metabolism (3,4). Astrocytes are a site of prevalent glucose uptake (5), as well as lactate formation and release (6,7).…”