THE ACTION OF AMMONIA ON ASTROCYTE GLYCOGEN AND GLYCOGENOLYSIS

Most of the brain glycogen, a major energy reserve that can be mobiliz ed in response to increased neuronal activity, resides in the astrocyt e, the site of the neuropathological abnormality found in hepatic ence phalopathy (HE). Ammonia, a neurotoxin implicated in the pathogenesis of HE, has been reported to cause a depletion of glycogen in primary a strocyte cultures. To further investigate the action of ammonia on gly cogen levels, cultured astrocytes were exposed to ammonium chloride (1 -5 mM) for various times up to 7 d. Treatment with ammonia for 24 h di d not alter deoxyglucose uptake, but significantly lowered peak glycog en values (found at 1.5 h following feeding with medium containing 5.5 mM glucose) in a concentration-dependent manner. This inhibitory effe ct was not observed after longer exposure times to ammonia. Three day treatment of cells did, however, significantly reduce norepinephrine-s timulated glycogenolysis, an effect not seen after 1 d of ammonia trea tment. Part of the neurotoxic action of long term ammonia exposure in humans and experimental animals may be to inhibit the breakdown of gly cogen. The effect of ammonia on astrocyte glycogen synthesis and/or br eakdown may disrupt glial neuronal signaling and thus play a role in t he pathogenesis of HE.