An ultrastructural study of methionine sulphoximine-induced glycogen accumulation in astrocytes of the mouse cerebral cortex

Abstract

Glycogen distribution in the mouse cerebral cortex was examined with electron microscopy following treatment with the experimental convulsant, methionine sulphoximine (M.S.O.). Both at 24 and 48 h followed administration of M.S.O., accumulation of particulate glycogen was prominent in astrocytes throughout the cerebral cortex. In astrocyte cell bodies and in subpial, pericapillary and perineuronal astrocyte processes the glycogen often completely filled the cytoplasm, crowding the remaining organelles and inclusions. The present findings correlate well with biochemical studies of M.S.O. effects of glutamine synthetase activity and energy metabolism. It is suggested that the glycogen may be derived from glutamate which under normal conditions would be converted to glutamine.

Glial Glycogen Stores Affect Neuronal Survival during Glucose Deprivation in vitro

“…Glutamine synthetase, like gly cogen, is localized in brain primarily to astrocytes , 1977), and evidence suggests that the glycogen accumulation caused by MSO may be a secondary consequence of glu tamine synthetase inhibition (Swanson et al, 1990a). MSO administration to rats in vivo causes brain glycogen accumulation only in glia (Phelps, 1975).…”

“…First, cortical astrocytes in vivo and in culture are known to contain substantial amounts of glycogen (Cataldo and Broadwell, 1986;Rosenberg and Dichter, 1987) whereas neurons both in adult brain (Koizumi, 1974;Phelps, 1975;Cataldo and Broadwell, 1986) and fetal brain (Bruckner and Biesold,198 1) have negligible glycogen stores. Second, we observed much higher glycogen levels in glial-confluent cul tures containing both NSE-positive neurons and GF AP-positive astrocytes than in glial-poor cul tures containing predominantly NSE-positive neu rons.…”

“…The major energy reserve in brain is glycogen (Lowry et aI., 1964), accounting for about 65% of ATP that can be generated under ischemic conditions. Almost all of this glycogen is localized to astrocytes, with other glial elements and neurons having minimal stores (Koizumi, 1974;Phelps, 1975;Cataldo and Broadwell, 1986).…”

Fuelling Cerebral Activity in Exercising Man

“…Secondarily, glycogen can maintain the glucose concentration in the extracellular fluid (Dringen and Hamprecht, 1992). Glycogenolysis may also provide energy for inactivation of glutamate via glutamine (Phelps, 1975). Glycogen turnover seems pronounced in areas of high metabolic capacity (Pfeiffer et al, 1990;Swanson et al, 1992); thus, glycogen is integral in cerebral metabolism, with the level decreasing during cerebral activation (Madsen et al, 1999;Swanson et al, 1992), as mediated by the neurotransmitters noradrenaline, VIP and serotonin, and various byproducts of activity, viz.…”

“…Glycogen is confined mainly to the astrocytes (Cataldo and Broadwell, 1986;Koizumi, 1974;Phelps, 1975), where its breakdown feeds glycolysis and lactate production (Brown et al, 2003;Dringen et al, 1993) (Figure 10). Secondarily, glycogen can maintain the glucose concentration in the extracellular fluid (Dringen and Hamprecht, 1992).…”