EXAGGERATED ASTROCYTE REACTIVITY AFTER NIGROSTRIATAL DEAFFERENTATION IN THE AGED RAT

Although clinical experience suggests that brain injury in the aged is associated with a poor prognosis, little research has examined this p henomenon at a cellular or molecular level. Unilateral B-hydroxydopami ne lesions of the nigrostriatal system were produced in 6-, 15- or 24- month-old rats. In the deafferented neostriatum, the time-dependent in duction of glial fibrillary acidic protein (GFAP) was larger and persi sted longer in the aged rats. The response of middle-aged rats was int ermediate. In contrast, no induction of S-100 or glutamine synthetase was observed in any age group. In a second series of rats with stab wo unds in the neostriatum, there were substantially larger GFAP inductio ns than after deafferentation, but fewer effects of age. However, in b oth lesion paradigms, GFAP staining increased in the contralateral str iatum of old rats, but not in young rats. These data support and exten d our earlier work describing larger GFAP RNA inductions after fornix transections in aged mouse hippocampus. The consistency of this exagge rated glial reactivity in the aged brain after modest injury suggests the following: 1) aged astrocytes are more sensitive to gliotrophic fa ctors released by terminal degeneration, 2) larger quantities of such factors are produced after injury, 3) clearance of these factors is de layed in old rodents, and/or 4) aged astrocytes are less able to termi nate GFAP inductions after activation. Given the potential role of inf lammatory reactions as pathogenic mechanisms in Alzheimer's dementia, these data suggest that age-related glial hypersensitivity may indepen dently increase the risk for some degenerative diseases. (C) 1997 Wile y-Liss, Inc.