glycogen phosphorylase inhibitor selectively enhances local rates of glucose utilization in brain during sensory stimulation of conscious rats: implications for glycogen turnover

• Published in: Journal of neurochemistry Vol. 102; no. 2; pp. 466 - 478
• Main Authors: Dienel, Gerald A, Ball, Kelly K, Cruz, Nancy F
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01-07-2007; Blackwell Publishing Ltd; Blackwell
• Subjects: Acoustic Stimulation; Afferent Pathways - metabolism; Animals; Biochemistry and metabolism; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Brain; Brain - anatomy & histology; Brain - metabolism; brain activation; brain imaging; Carbon Radioisotopes - metabolism; Central nervous system; Chemistry; Citric Acid Cycle - drug effects; Citric Acid Cycle - physiology; Consciousness - physiology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; energetics; Energy Metabolism - physiology; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Glucose; Glucose - metabolism; glucose utilization; Glycogen - metabolism; Glycogen Phosphorylase, Brain Form - antagonists & inhibitors; Glycogen Phosphorylase, Brain Form - metabolism; glycogenolysis; Inhibitor drugs; Lactic Acid - metabolism; Male; Medical sciences; Neurology; Photic Stimulation; Physical Stimulation; Pyruvic Acid - metabolism; Rats; Rats, Wistar; Rodents; Sensation - physiology; sensory stimulation; Up-Regulation - physiology; Vertebrates: nervous system and sense organs; Rat; Glycosyltransferases; Central nervous system; Activation; Glucose; Blood; Encephalon; sensory stimulation; Parietal cortex; Release; energetics; brain imaging; Enzyme; Transferases; Rodentia; glucose utilization; Pyruvate; brain activation; Phosphorylase; Lactates; Vertebrata; Mammalia; Treatment; glycogenolysis; Hexosyltransferases; Emergency
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2007.04595.x

Glycogen is degraded during brain activation but its role and contribution to functional energetics in normal activated brain have not been established. In the present study, glycogen utilization in brain of normal conscious rats during sensory stimulation was assessed by three approaches, change in concentration, release of ¹⁴C from pre-labeled glycogen and compensatory increase in utilization of blood glucose (CMRglc) evoked by treatment with a glycogen phosphorylase inhibitor. Glycogen level fell in cortex, ¹⁴C release increased in three structures and inhibitor treatment caused regionally selective compensatory increases in CMRglc over and above the activation-induced rise in vehicle-treated rats. The compensatory rise in CMRglc was highest in sensory-parietal cortex where it corresponded to about half of the stimulus-induced rise in CMRglcf in vehicle-treated rats; this response did not correlate with metabolic rate, stimulus-induced rise in CMRglc or sequential station in sensory pathway. Thus, glycogen is an active fuel for specific structures in normal activated brain, not simply an emergency fuel depot and flux-generated pyruvate greatly exceeded net accumulation of lactate or net consumption of glycogen during activation. The metabolic fate of glycogen is unknown, but adding glycogen to the fuel consumed during activation would contribute to a fall in CMRO₂/CMRglc ratio.