The fibroblast growth factor (FGF) family of proteins is comprised of nine currently identified members. These proteins are noted for their wide distribution throughout numerous tissues and for their multifuncional biological activities. At least three of these proteins (acidic FGF, basic FGF and FGF5) have been shown to have neurotrophic activity . In addition, relatively large amounts of these proteins have been isolated from brain tissue in a variety of species. Much of the information currently available regarding the neurotrophic activities of these molecules has been obtained through studies of their activity in primary neuronal cultures. Little is known about the distribution and function of these trophic factors in vivo . The reports available regarding localization of the FGF mRNAs and protein in the brain are fragmentary and contradictory. The objective of the current project is to describe the precise anatomical distribution of the mRNA for each of the FGF proteins in the normal adult rat brain using in situ hybridization. In addition, in situ hybridization is being used to localize mRNA for the four currently identified FGF receptors in the brain. Further, through the use of use of well characterized animal models of neurodegeneration, study of in vivo regulation of FGF mRNAs in reponse to injury is being pursued. The current focus of these studies is on describing the differential distribution of mRNA for aFGF, bFGF and FGF5 due to their known neurotrophic activity. Using radiolabeled cRNA probes which recognize each of these trophic factor and receptor mRNAs, in situ hybridization is being performed on serially cut, slide mounted tissue sections from rodent brain. The radiolabeled sections are exposed to x-ray film or liquid emulsion and the resulting autoradiograms are anayzed using computer assisted image analysis. In addition, localization of each trophic factor protein is being performed on similar tissue sections using immunocytochemisry to compare the distributions of the mRNA and protein for each of the FGF neurotrophic factors. These studies will provide critical information regarding the localization and differential distribution of the FGF family of proteins in the mammaliam brain and identify potentially reponsive brain regions and cell groups which may be physiological targets for their action.
