|[Frontiers in Bioscience 2, d88-125, March 1, 1997]|
CROSS-TALK SIGNALS IN THE CNS: ROLE OF NEUROTROPHIC AND HORMONAL FACTORS, ADHESION MOLECULES AND INTERCELLULAR SIGNALING AGENTS IN LUTEINIZING HORMONE-RELEASING HORMONE (LHRH)-ASTROGLIAL INTERACTIVE NETWORK|
Department of Pharmacology, Medical School, University of Catania, 95125 Catania, Laboratory of Biotech. Neuropharmacology, OASI Institute for Research and Care (IRCCS) on Mental Retardation and Brain Aging (IRCCS) Troina, (EN), Italy.
Received 8/2/96; Accepted 2/20/97; On-line 3/1/97
Basic fibroblast growth factor is known to be present in the telencephalon as early as E9.5 and in the cerebral cortex throughout neurogenesis and into adulthood (70, 249-251). Moreover, bFGF is known to stimulate the division of committed neuronal progenitor cells derived from olfactory epithelium (82). Such findings are of special interest and potential implications in the genesis of LHRH neurons and glia, because both cell types are derived from the olfactory placode. Peptide growth factors released by olfactory bulb glia represent a strong neurotropic stimulus for the GT1 cell line (41). Basic fibroblast growth factor is associated with extracellular matrix and cell membranes and has been suggested as possible candidate mediating cell-cell contacts (251, 252). Our recent study showed that neutralization of bFGF action during GT1-1 neuron-astroglia interactions, produced a significant inhibition of astroglia neurotrophic effect (44). Such result indicates that endogenous bFGF of neuronal and/or astroglial origin as a candidate molecule in such crosstalk. These data are of particular interest in the light of the recent discovery of a paracrine bFGF system, endogenous to the GT1-1 neuron (253). Indeed, using RNAse protection assays and riboprobes specific for murine FGF receptors 1-3, these authors showed that GT1-1 do express FGF receptors, and that occupancy of these receptors by bFGF stimulated the sustained tyrosine phosphorylation of both the 42- and 44-kilodalton mitogen-activated protein kinases (MAPKs) for up to 6 hours (253). In addition, the GT1 cells were also shown to express mRNA for bFGF (261), but at low levels, possibly due to an instability of the bFGF mRNA (253). It should be noted that bFGF lacks a signal peptide (254), and it is unclear if bFGF synthesized by the GT1 cells is released as a biologically active peptide and/or the GF needs further processing. Recent studies have, however, indicated that bFGF-like peptides are released by cultured neuronal and glial cells (255). Moreover, the release of astroglial bFGF may be influenced by other GFs (see 59). The available information raises the possibility that bFGF possibly acting in partnership with LHRH and other GFs of neuronal and/or astroglial origin, may modulate/drive GT1 neuronal differentiation. That growth factors play a prominent role through their cooperation with auxiliary agents has been suggested (see 256-259). Indeed, Iacovitti and coworkers (257, 258) hypothesized that the catecholaminergic (CA) neurons may harbor or have local access to all of the agents necessary for their biochemical differentiation. Induction of the CA-specific gene, tyrosine hydroxylase, has been recently shown to be mediated by a novel mechanism requiring the simultaneous actions of both aFGF and the enzyme's catalytic end products, the CA (257). This could then represent a more general mechanism in the regulation of neuronal phenotype differentiation during development, and in the adult brain.