ENHANCED GLIAL FIBRILLARY ACIDIC PROTEIN RNA RESPONSE TO FORNIX TRANSECTION IN AGED MICE

The effects of age on basal and lesion-induced changes in astrocyte RN A messages reported to respond to neurodegeneration were examined in t he mouse brain. The first study found an age-related increase in glial fibrillary acidic protein RNA throughout the brain. Other astrocyte R NAs remained generally stable with age. We hypothesize this increase i s due to astrocytes undergoing a mild reaction to the small amount of synaptic degeneration occurring with usual aging. To test this theory, we used an experimental model of modest synaptic loss in the hippocam pus by transecting the fimbria/fornix bundle in mice and examined the same series of messages. In situ hybridization revealed the expected i ncrease in glial fibrillary acidic protein RNA after the lesion; howev er, we unexpectedly found that aged mice showed a greater magnitude of this response, which appeared to develop more slowly. There was no si gnificant change in the hippocampus for any of the other messages, alt hough responses were observed at the site of transection. This study s upports the idea that the age-related increase in glial fibrillary aci dic protein may be secondary to modest synaptic degeneration. We also demonstrated an exaggerated reactive astrocytic response in aged mice, which may be associated with age-related deficits in reactive synapto genesis and behavioral recovery in normal aging.