Astroglial and fibroblast growth factors have neurotrophic functions for cultured peripheral and central nervous system neurons.

Abstract

Embryonic and neonatal neurons require specific trophic supplements for their survival and the induction of transmitter-synthesizing enzymes in vivo and in vitro. Acidic and basic fibroblast growth factor (aFGF, bFGF) and the closely related astroglial growth factors AGF-1 and AGF-2 were studied for putative neurotrophic functions using dissociated, highly neuron-enriched cultures from chick and rat peripheral ganglia and central nervous system tissues. Embryonic chick ciliary ganglion neurons were the only peripheral neurons that responded to bFGF and AGF-2 by enhanced survival equivalent to that obtained with ciliary neurotrophic factor. Half-maximal effects were achieved with bFGF at 360 pg/ml or AGF-2 at 3 ng/ml. Small effects seen with aFGF could be potentiated by adding heparin at 1 ,ug/ml. bFGF, but not ciliary neurotropic factor, also promoted neuron survival after the factor was bound to polyornithine and laminin. Both AGF-2 and ciliary neurotropic factor induced choline acetyltransferase activity during 48 hr. AGFs and FGFs also enhanced the long-term survival of embryonic chick spinal cord neurons, including motoneurons that had been retrogradely labeled with rhodamine isothiocyanate. These results demonstrate the potency of a class of mitogenic growth factors as neurotrophic agents for embryonic ciliary ganglion and spinal cord neurons-adding to the emerging evidence that mitogenic and neuronal growth factors are not strictly separate entities.Mitogenic, growth-promoting factors for cells derived from the mesoderm (e.g., fibroblast growth factors, FGFs) and neurotrophic factors (the prototype of which is nerve growth factor) that promote survival, differentiation, and functional maintenance of neurons have long been considered as separate entities. Emerging evidence suggests that this view can no longer strictly be maintained. Thus, nerve growth factor has been shown to act as a mitogen on rat pheochromocytoma (1) and adrenal medullary chromaffin cells (2). On the other hand, FGF and astroglial growth factors (AGF-1 and -2) that are closely related or even identical to acidic and basic FGF (aFGF, bFGF) (3) induce proliferation and differentiation of neuroectodermal astroglial cells (4), oligodendrocytes (5, 6), and neuron-like PC-12 pheochromocytoma cells (7).Large amounts of FGF are found in brain (8-10), and immunocytochemical studies using antibodies to AGF/FGF have revealed their localization in neurons of the central nervous system (11). We therefore questioned whether AGF and FGF had functions in the nervous system in addition to their established role for glial cells.We provide evidence that AGF and FGF mimic two effects typical of neurotrophic factors-promotion of in vitro neuron survival and enhancement of the activity of a transmittersynthesizing enzyme, choline acetyltransferase (ChoAcTase, acetyl-CoA:choline O-acetyltransferase, EC 2.3

Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor

“…la ) revea ls a Cterminally ex tended product. CNTF, rather, see ms 10 be a molecule simil ar to FGF o r interleukin-l (lL-l ) both of wh ich exert profound effects on cells but are cytoplasmic proteins. For FGF, no release mechani sm has been estab lished 12 , By contrast, IL-l has been demonstrated 10 be released from stimul ated Amino-acid composition of CNTF.…”

High molecular weight forms of basic fibroblast growth factor recognized by a new anti‐bFGF antibody

“…Neurotrophic activity of bFGF-enriched fractions was tested in a bioassay using chick ciliary ganglionic neurons of embryonic day 8 (cCG 8) [6]. To establish plateau survival values we used saturating concentrations of purified or recombinant bovine bFGF [6] (recombinant bFGF was kindly provided by PROGEN, Heidelberg) or CNTFcontaining cell-free extracts from selected embryonic chick eye tissues (CIPE) (221.…”

“…To establish plateau survival values we used saturating concentrations of purified or recombinant bovine bFGF [6] (recombinant bFGF was kindly provided by PROGEN, Heidelberg) or CNTFcontaining cell-free extracts from selected embryonic chick eye tissues (CIPE) (221. Culture medium without trophic factors served as the baseline control.…”

Interaction of FGF-2 with IGF-1 and BDNF in stimulating Akt, ERK, and neuronal survival in hippocampal cultures

“…The peptide has been demonstrated to have a role in stimulating hippocampal neurogenesis (Palmer et al, 1999) and, and in some model systems, has been reported to have neurotrophic actions. For example FGF-2 promotes survival of cultured cerebellar granule cells (Bonthius et al, 2003) as well cultured embryonic chick ciliary ganglion neurons and cultured spinal chord neurons (Unsicker et al, 1987). It has been additionally reported to enhance survival of hippocampal neurons in culture (Walicke et al, 1986), and to confer protection from glutamate-induced cell death (Mattson et al, 1995;Lenhard et al, 2002).…”