Epidermal growth factor exerts neuronotrophic effects on dopaminergic and GABAergic CNS neurons: Comparison with basic fibroblast growth factor (original) (raw)
Related papers
Neuroscience, 1993
We have studied the effects of basic fibroblast growth factor on rat embryonic mesencephalic neurons in vitro. Basic fibroblast growth factor promotes the survival of dopaminergic neurons in vitro, the effect increasing with dose and reaching a maximum at 10 ng/ml. In the absence of basic fibroblast growth factor the number of tyrosine hydroxylase-stained (tyrosine hydroxylase positive) neurons declines to almost zero within 14 days, whereas in the presence of basic fibroblast growth factor numbers remain almost constant from three to 28 days in vitro. This effect of basic fibroblast growth factor is abolished by preventing non-neuronal cells from appearing in the cultures, apart from a basic fibroblast growth factor-mediated increase in the numbers of tyrosine hydroxylase-positive cells during the first two days in vitro. The presence or absence of non-neuronal cells also influences dopaminergic neuronal morphology, the neurons having more, longer, and more varicose processes in the absence of astrocytes. Survival of dopaminergic neurons in vitro in the absence of basic fibroblast growth factor is very dependent on plating cell density, but in the presence of basic fibroblast growth factor this dependency vanishes. It is also possible to make survival independent of plating density by growing the cultures on inverted coverslips, which have the effect of concentrating secreted molecules in the thin layer of medium between coverslip and dish. Our conclusions from these experiments on plating density are that astrocytes probably constitutively secrete a small amount of a trophic factor which promotes survival of dopaminergic neurons, and that the rate of production of this factor is greatly increased by basic fibroblast growth factor. If basic fibroblast growth factor is withdrawn from cultures after two or seven days the dopaminergic neurons soon die. However, if basic fibroblast growth factor is withdrawn after 14 days, after the period of naturally occurring cell death of these neurons, there is no increase in dopaminergic neuronal death compared to controls in which basic fibroblast growth factor treatment is maintained. If basic fibroblast growth factor is used to improve the survival of dopaminergic neurons grafted in vivo, it should therefore be sufficient to treat the grafts for 14 days.
The Journal of Neuroscience, 1990
To study the selectivity of neurotrophic actions in the brain, we analyzed the actions of several known growth factors on septal cholinergic, pontine cholinergic, and mesencephalic dopaminergic neurons in culture. Similar to nerve growth factor (NGF), basic fibroblast growth factor (bFGF) stimulated choline acetyltransferase activity in septal cultures. In contrast to NGF, bFGF also enhanced dopamine uptake in mesencephalic cultures and stimulated cell proliferation in all 3 culture types. Insulin and the insulin-like growth factors I and II stimulated transmitter-specific differentiation and cell proliferation in all culture types. Epidermal growth factor (EGF) produced a small increase in dopamine uptake by mesencephalic cells and stimulated cell proliferation in all culture types. In septal cultures, bFGF was most effective when given at early culture times, NGF at later times. The stimulatory actions of bFGF and insulin did not require the presence of glial cells and were not me...
Developmental Brain Research, 1988
Basic and acidic fibroblast growth factors (bFGF, aFGF) increase the survival of fetal hippocampal pyramidal neurons in serumfree cultures, bFGF is also a mitogen for astrocytes either in highly purified glial cultures or as a contaminant in neuronal cultures. The possibility that bFGF enhances neuronal survival indirectly through stimulating glial proliferation is unlikely. In the presence of 1 ng/ml bFGF, the total number of contaminating astrocytes (as defined by immunohistochemical staining for glial fibrillary acidic protein (GFAP)) was increased to 4.3% vs 0.9% in control hippocampal cultures, aFGF did not significantly increase astrocyte number while supporting neuronal survival. Two other agents which stimulated equal or greater astrocytic proliferation, epidermal growth factor (EGF) and 10% serum, did not support neurons, and bFGF still significantly increased neuronal survival in their presence. When glial proliferation was inhibited by aphidicolin, contamination decreased to 0.1% in controls and 1.0% with 1 ng/ml bFGF, yet the neurons remained responsive to FGF. Cultures lacking any detectable GFAP-positive cells were identified, and even in the absence of glial cells, aFGF and bFGF increased neuronal survival. Because there is no significant correlation between the neuronal response and astrocyte number, it appears that bFGF and aFGF can directly support neuronal survival.
The role of epidermal growth factor and its receptors in mammalian CNS
Cytokine & Growth Factor Reviews, 2004
Epidermal growth factor (EGF) is a common mitogenic factor that stimulates the proliferation of different types of cells, especially fibroblasts and epithelial cells. EGF activates the EGF receptor (EGFR/ErbB), which initiates, in turn, intracellular signaling. EGFR family is also expressed in neurons of the hippocampus, cerebellum, and cerebral cortex in addition to other regions of the central nervous system (CNS). EGF enhances the differentiation, maturation and survival of a variety of neurons. Transgenic mice lacking the EGFR developed neurodegenerative disease and die within the first month of birth. EGF acts not only on mitotic cells but also on postmitotic neurons, and many studies have indicated that EGF has neuromodulatory effect on various types of neurons in the CNS. This review highlights some of the major recent findings pertinent to the EGF and ErbB family with special references to elucidating their roles in the regulation of neurogenesis, signal transduction and trafficking and degradation.
Science, 1984
Epidermal growth factor (EGF) is a potent mitogen with hormonal activity in the gastrointestinal tract. Material cross-reacting with EGF was detected in the central nervous system of the developing and adult albino rat by the indirect immunofluorescence technique. High concentrations ofEGF-cross-reacting material were identified in forebrain and midbrain structures ofpallidal areas of the brain. These include the globus pallidus, ventral pallidum, entopeduncular nucleus, substantia nigra pars reticulata, and the islands of Calleja. Thus, EGF may represent another gut-brain peptide with potential neurotransmitter-neuromodulatorfunctions in pallidal structures of the extrapyramidal motor systems of the brain.
Journal of Neurochemistry, 2004
Glial growth factor-2 (GGF2) and other neuregulin (NRG) isoforms have been shown to play important roles in survival, migration, and differentiation of certain neural and non-neural cells. Because midbrain dopamine (DA) cells express the NRG receptor, ErbB4, the present study examined the potential neurotrophic and/or neuroprotective effects of GGF2 on cultured primary dopaminergic neurons. Embryonic day 14 rat mesencephalic cell cultures were maintained in serum-free medium and treated with GGF2 or vehicle. The number of tyrosine hydroxylase-positive (TH+) neurons and high-affinity [ 3 H]DA uptake were assessed at day in vitro (DIV) 9. Separate midbrain cultures were treated with 100 ng/mL GGF2 on DIV 0 and exposed to the catecholamine-specific neurotoxin 6-hydroxydopamine (6-OHDA) on DIV 4. GGF2 treatment significantly increased DA uptake, the number of TH+ neurons, and neurite outgrowth when compared to the controls in both the serum-free and the 6-OHDA-challenged cultures. Furthermore, three NRG receptors were detected in the midbrain cultures by western blot analysis. Immunostaining for glial fibrillary acidic protein revealed that GGF2 also weakly promoted mesencephalic glial proliferation in the midbrain cultures. These results indicate that GGF2 is neurotrophic and neuroprotective for developing dopaminergic neurons and suggest a role for NRGs in repair of the damaged nigrostriatal system that occurs in Parkinson's disease.
On the functional role of polypeptide growth factors in rodent neurobehavioral development
Acta Neurobiol. Exper, 1990
A number of polypeptide growth factor molecules have been discovered and characterized in the recent years. Most of thelm appear to play important roles in the ontogeny of bo,th vertebrates and invertebrates, and some growth factors are specifically involved in brain development of altricial mammals such as rats and mice. In particular, Nerve Growth Factor (NGF) seems to be involved in degenerative processes of the aged CNS and to control brain development, particularly cholinergic systems. Data concerning NGF effects on neurobehavioral development of neonatal mice are reported, and compared with the specific alterations caused by neonatal Epidermal Growth Factor (EGF) e x p u r e on a number of physical and behavioural scores. While NGF mainly anticipated behavioural development, EGF exerted both growth-prolm~oting and growth-inhibiting effects.
Basic fibroblast growth factor in neuronal cultures of human fetal brain
Journal of Neuroscience Research, 1990
The presence of basic fibroblast growth factor (bFGF) was investigated in neuronal cells derived from 12 and 18 week-old human fetal brain cultures. To this purpose, the ability of bFGF to stimulate plasminogen activator (PA) production in fetal bovine aortic endothelial GM 7373 cells was used as an assay for this molecule in neuronal cell extracts. The identity of the PA-stimulating activity of neuronal cell extract with bFGF was confirmed by its high affinity for heparin and by its cross-reactivity with polyclonal antibodies to human placental bFGF. These antibodies recognized a Mr 18,000 cell-associated protein both in Western blot and in immuno-precipitation experiments. All the neurons showed bFGF immunoreactivity, as demonstrated hy immunocytochemical staining, while nonneuronal cells were unstained. The data demonstrate for the first time that cultured human fetal brain neurons contain and synthesize bFGF.
Experimental Brain Research, 1993
The effect of two isoforms of platelet-derived growth factor (PDGF), PDGF-AA and PDGF-BB, was tested on dissociated cell cultures of ventral mesencephalon from rat and human embryos. PDGF-BB but not PDGF-AA reduced the progressive loss of tyrosine hydroxylase-(TH)-positive neurons in rat and human cell cultures. The mean number of TH-positive cells in the PDGF-BB-treated rat culture was 64% and 106% higher than in the control cultures after 7 and 10 days in vitro, respectively. Corresponding figures for human THpositive neurons were 90% and 145%. The influence of PDGF-BB was specific for TH-positive neurons and not a general trophic effect, since no change of either total cell number or metabolic activity was found. In PDGF-BB-treated cultures of human but not rat tissue the TH-positive neurons had longer neurites than observed in control or PDGF-AA-treated cultures. These data indicate that PDGF-BB may act as atrophic factor for mesencephalic dopaminergic neurons and suggest that administration of PDGF-BB could ameliorate degeneration and possibly promote axonal sprouting of these neurons in vivo.