Technical and Comparative Aspects of Brain Glycogen Metabolism

Abstract

It has been known for over 50 years that brain has significant glycogen stores, but the physiological function of this energy reserve remains uncertain. This uncertainty stems in part from several technical challenges inherent in the study of brain glycogen metabolism, and may also stem from some conceptual limitations. Factors presenting technical challenges include low glycogen content in brain, nonhomogenous labeling of glycogen by radiotracers, rapid glycogenolysis during postmortem tissue handling, and effects of the stress response on brain glycogen turnover. Here, we briefly review aspects of glycogen structure and metabolism that bear on these technical challenges, and discuss ways these can be overcome. We also highlight physiological aspects of glycogen metabolism that limit the conditions under which glycogen metabolism can be useful or advantageous over glucose metabolism. Comparisons with glycogen metabolism in skeletal muscle provide an additional perspective on potential functions of glycogen in brain.

Disrupted Cerebral Peri-Microvascular Glycogen Promotes Capillary Constrictions and Aggravates Ischemia in Mice

“…We found that disruption of glycogen mobilization either pharmacologically or genetically, via DAB and GYS-1 NestinKO respectively lead to microvascular constrictions, ultimately suggesting that disturbed glycogen metabolism can cause ischemic-like phenotype in the brain under non-ischemic circumstances. Although it has been shown in various studies that glycogen has essential roles in the brain, investigating the regional differences has been an issue because of the difficulties of quantification, and demonstrating in the tissue (37–39). Our ex vivo data which was analyzed by semi-stereological methods to overcome this regional heterogeneity showed that CD13-positive pericytes were localized at constriction sites in accordance with our previous results showing that pericytes have an important role causing microvascular constrictions after cerebral and retinal ischemia (17, 19).…”