Glycogen is a preferred glutamate precursor during learning in 1‐day‐old chick: Biochemical and behavioral evidence

Abstract

Bead discrimination training in chicks sets in motion a tightly timed series of biochemical events, including glutamate release, increase in forebrain level of glutamate and utilization of glycogen and glucose. Inhibition of glycogen breakdown by the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB) around the time of training abolishes the increase in glutamate 5 min posttraining in the left hemisphere, in spite of uninhibited glucose metabolism. It also reduces the contents of glutamate, glutamine, and aspartate in the right hemisphere. Behavioral evidence supports the conclusion that glucose breakdown serves to provide energy, whereas glycogen acts as a substrate for glutamate, glutamine, and aspartate formation, requiring both pyruvate dehydrogenation to acetyl coenzyme A and pyruvate carboxylation in astrocytes. Inhibition of memory consolidation caused by DAB or 2-deoxyglucose (2-DG), an inhibitor of glucose phosphorylation without effect on glycogen metabolism, was challenged by intracerebral administration of acetate, aspartate, glutamine, lactate or glucose. DAB-mediated memory inhibition was successfully challenged by administration at 0 or 20 min posttraining of acetate (an astrocyte-specific acetyl CoA precursor) together with aspartate, substituting for pyruvate carboxylation, or of glutamine at 0-2.5 or 30 min posttraining. 2-DG-mediated memory impairment was not challenged by acetate with or without aspartate at 0 time but was challenged by acetate without aspartate at 20 min. Lactate, a substrate for both dehydrogenation and pyruvate carboxylation challenged both DAB and 2-DG. Doses of DAB and 2-DG which, on their own were subeffective, were not additive, further supporting the existence of one pathway using glucose and another using glycogen.

Role of β-Adrenoceptors in Memory Consolidation: β3-Adrenoceptors Act on Glucose Uptake and β2-Adrenoceptors on Glycogenolysis

“…This supports the idea that glycolysis and glycogenolysis are compartmentalized in astrocytes (Sickmann et al, 2005;Gibbs et al, 2007).…”

A Subconvulsive Dose of Kainate Selectively Compromises Astrocytic Metabolism in the Mouse Brain In Vivo

“…It should be noted, however, that although glycogen is confined to astrocytes, 39 it is also able to sustain energy homeostasis in neurons via conversion to lactate and transfer to the neuronal compartment for reconversion to pyruvate entering the TCA cycle for energy production. In addition, it has been demonstrated that glycogen is an important precursor for de novo synthesis of glutamate and glutamine, 40 i.e., for maintenance of cerebral amino-acid homeostasis. Accordingly, glycogen may be important as an energy substrate and/or as a precursor for amino-acid biosynthesis during seizure activity.…”

Immunohistochemical Localization of Glycogen Phosphorylase Isozymes in the Rat Gastrointestinal Muscle Layers and Enteric Nervous System

“…It is thought of as an emergency fuel store during physiological and pathological stress such as hypoglycaemia or cerebral ischemia [6,7]. However, additional roles have been ascribed to glycogen: It can provide energy for rapid clearance by astrocytes of the neurotransmitter glutamate [8], serve as precursor of the carbon skeleton of glutamate [9], and provide NADPH for the disposal of peroxides in astroglial cultures [10]. In fact, the role of glycogen as an important component of normal brain metabolism is now under discussion [11].…”