Fibroblast growth factors (FGF) are polypeptide growth factors with potent effects on several cell types in the mammalian central nervous system (CNS), including neurons, glia, and endothelial cells. Both acidic and basic forms exist. Recent evidence suggests that FGF may play an important role in the development, plasticity, and repair of the mammalian brain. Further because of their relative abundance and protean effects on CNS cells, FGF are also likely to play an important role in brain aging. Indeed, in vitro studies suggest that FGF can prolong the survival and delay the senescence of cultured cells. The proposed studies will specifically address the role of FGF within the mature and aging mammalian (rodent) brain. They will examine the in situ expression, receptors, and effects of both acidic and basic FGF, and address the hypotheses that these change with aging. The levels and cellular distribution of FGF will be studied by bioassay, immunoassay, and immunohistochemical techniques. The levels and cellular distribution of FGF mRNA will be studied by Northern blotting and in situ hybridization techniques. The cellular distribution and density of FGF receptors will be studied by in situ autoradiographic techniques. These studies will also test the in vivo effects of FGF when directly applied to the mature and aging brain. Pilot studies will be continued on the levels and distribution of FGF in human brain, including Alzheimer Disease (AD). In particular, these studies will follow-up on preliminary observations of increased levels of FGF in affected regions of AD brain. These studies will increase our understanding of the role of FGF in the mammalian brain, as well as possible changes in the expression or effects of FGF with brain aging and disease. Such changes may have profound effects on cellular maintenance, plasticity, and repair in the aged brain, and may be potentially reversible by the administration of FGF or agents that potentiate their effects.
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