AN ALUMINUM-INDUCED INCREASE IN GFAP IS ATTENUATED BY SOME CHELATORS

Enhanced expression of glial fibrillary acidic protein (GFAP) has been shown to be associated with gliosis, a generic response of the CNS to neural injury. The effects of aluminum (Al) on regional GFAP concentr ations were evaluated to determine potential sites of Al-induced neura l injury. Rabbits received 20 Al (100 mu mol/kg) or sodium lactate inj ections over 1 month. Frontal cortical GFAP increased (approximate to twofold above control) in Al-loaded rabbits, whereas hippocampal and c erebellar GFAP concentrations were not affected. Frontal cortical syna ptophysin, neurofilament 68, and myelin basic protein concentrations w ere then examined in an attempt to determine cell-specific targets of Al neurotoxicity. These proteins were not affected by Al. The ability of chelators to influence brain Al concentrations and the Al effect on GFAP were assessed. Desferrioxamine (DFO) and six 3-hydroxypyridin-4- ones (CPs) were given 12 times, over 1 month, to Al-loaded rabbits. CP 24 significantly reduced brain Al. CP93, CP52 and CP24 significantly r educed frontal cortical GFAP. The data suggest an Al-induced gliosis c onsequent to subtle damage in the frontal cortex and a protective role of some chelators against this CNS injury. (C) 1998 Elsevier Science Inc.