Abstract
The effects of basic fibroblast growth factor (bFGF) and ganglioside GM1 (GM1) were evaluated alone and simultaneously in two types of experiments. First, the neuronal survival of primary culture neurons from fetal rat brain was measured. Then, performance on radial maze task in adult male rats following bilateral partial Fimbria-Fornix transections (F-F lesion) was tested. In primary culture neurons, bFGF (1–10 ng/ml) supported the neuronal survival from three regions (hippocampus, cortex and septum) of embryonic rat brain. However, GM1 (0.1–10 μg/ml) did not support the neuronal survival from any regions. Survival of cultured neurons was not supported by addition of 0.1 ng/ml bFGF, but when bFGF (0.1 ng/ml) and GM1 (0.1, 1 μg/ml) were given to the cultured neurons simultaneously, the number of surviving neurons increased significantly. In the eight-arm radial maze task, where only the same four arms were baited, F-F lesion produced substantial memory impairment. In this task, administration of bFGF (10 μg/ml) or GMl (1 mg/ml) alone did not produce any effects. However, when they were given simultaneously, the number of working memory errors decreased significantly, in spite of no amelioration for hippocampal choline acetyl transferase (ChAT) depletion. These findings indicate that actions of bFGF may be potentiated by the addition of GM1 in both primary neuronal cultures and radial maze task performance. These results suggest that the combination of bFGF and GM1 may synergistically improve spatial memory deficits.
Similar content being viewed by others
References
Abe K, Takayanagi M, Saito H (1990) Effects of recombinant human basic fibroblast growth factor and its modified protein CS23 on survival of primary cultured neurons from various regions of fetal rat brain. Jpn J Pharmacol 53:221–227
Anderson KJ, Dam D, Lee S, Cotman CW (1988) Basic fibroblast growth factor prevents death of lesioned cholinergic neurons in vivo. Nature 332:360–361
Barotte C, Eclancher F, Ebel A (1989) Effects of basic fibroblast growth factor (bFGF) on choline acetyltransferase activity and astroglial reaction in adult rats after partial fimbria transection. Neurosci Lett 101:197–202
Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254
Cannella MS, Oderfeld-Nowak B, Gradkowska M, Skup M, Garofalo L, Cuello AC, Ledeen RW (1990) Derivatives of Ganglioside GM1 as neurotrophic agents: comparison of in vivo and in vitro effects. Brain Res 513:286–294
Casamenti F, Bracco L, Bartolini L, Pepeu G (1985) Effects of ganglioside treatment in rats with a lesion of the cholinergic forebrain nuclei. Brain Res 338:45–52
Casamenti F, Di-Patre PL, Milan F, Petrelli L, Pepeu G (1989) Effects of nerve growth factor and GM1 ganglioside on the number and size of cholinergic neurons in rats with unilateral lesion of the nucleus basalis. Neurosci Lett 103:87–91
Cuello AC, Stephens PH, Tagari PC, Sofroniew MV, Pearson RC (1986) Retrograde changes in the nucleus basalis of the rat, caused by cortical damage, are prevented by exogenous ganglioside GM1. Brain Res 376:373–377
Cuello AC, Garofalo L, Kenigsberg RL, Maysinger D (1989) Gangliosides potentiate in vivo and in vitro effects of nerve growth factor on central cholinergic neurons. Proc Natl Acad Sci USA 86:2056–2060
Di-Patre PL, Casamenti F, Cenni A, Pepeu G (1989) Interaction between nerve growth factor and GM1 monosialoganglioside in preventing cortical choline acetyltransferase and high affinity choline uptake decrease after lesion of the nucleus basalis. Brain Res 480:219–224
Emerich DF, Walsh TJ (1990) Ganglioside AGF2 promotes task-specific recovery and attenuates the cholinergic hypofunction induced by AF64A. Brain Res 527:299–307
Fadda E, Negro A, Facci L, Skaper SD (1993) Ganglioside GM1 cooperates with brain-derived neurotrophic factor to protect dopaminergic neurons from 6-hydroxydopamine-induced degeneration. Neurosci Lett 159:147–150
Favaron M, Manev H, Alho H, Bertoline M, Ferret B, Guidotti A, Costa E (1988) Ganglioside prevents glutamate and kinate neurotoxicity in primary neuronal cultures of neonatal rat cerebellum and cortex. Proc Natl Acad Sci USA 85:7351–7355
Ferrari G, Batistatou A, Greene LA (1993) Gangliosides rescue neuronal cells from death after trophic factor deprivation. J Neurosci 13:1879–1887
Fonnum F (1975) A rapid radiochemical method for the determination of choline acetyltransferase. J Neurochem 24:407–409
Garofalo L, Cuello AC (1994) Nerve growth factor and the monosialoganglioside GM1: analogous and different in vivo effects on biochemical, morphological, and behavioral parameters of adult cortically lesioned rats. Exp Neurol 125:195–217
Gomez Pinilla F, Lee JW, Cotman CW (1992) Basic FGF in adult rat brain: cellular distribution and response to entorbinal lesion and fimbria-fornix transection. J Neurosci 12:345–355
Gradkowska M, Skup M, Kiedrowski, L, Calzolari S, Oderfeld-Nowak B (1986) The effect of GM1 ganglioside on cholinergic and serotonergic systems in the rat hippocampus following partial denervation is dependent on the degree of fiber degeneration. Brain Res 375:417–422
Grothe C, Otto D, Unsicker K (1989) Basic fibroblast growth factor promotes in vitro survival and cholinergic development of rat septal neurons: comparison with the effects of nerve growth factor. Neuroscience 31:649–661
Hisajima H, Miyagawa T, Saito H, Nishiyama N (1991) Human acidic fibroblast growth factor has trophic effects on cultured neurons from multiple regions of brain and retina. Jpn J Pharmacol 56:495–503
Karpiak SE (1983) Ganglioside treatment improves recovery of alternation behavior after unilateral entorhinal cortex lesion. Exp Neurol 81:330–339
Kunsel B, Michel PP, Schwaber JS, Hefti F (1990) Selective and nonselective stimulation of central cholinergic and dopaminergic development in vitro by nerve growth factor, basic fibroblast growth factor, epidermal growth factor, insulin and the insulin-like growth factors 1 and 2. J Neurosci 10:558–570
Lombardi G, Beni M, Curla V, Toffano G, Moroni F (1988) Differential actions of neurotrophic factors on lesion-induced damage of the serotonergic neurons projecting to the hippocampus. Brain Res 458:348–352
Marlier L, Poulat P, Konig N, Drian MJ, Privat A (1989) Influence of GM1 gangliosides on the growth of cultured rat embryonic serotonergic neurons. Int J Dev Neurosci 7: 655–665
Maysinger D, Jalsenjak K, Stolnik S, Garofalo L, Cuello AC, Jalsenjak I (1989) Micro encapsulated monosialoganglioside GM1: physical properties and in vivo effects. J Microencapsul 6:35–42
Maysinger D, Filipovic-Grcic J, Cuello AC (1993) Effects of coencapsulated NGF and GM1 in rats with cortical lesions. Neuroreport 4:971–974
Morrison RS, Sharma A, de-Vellis J, Bradshaw RA (1986) Basic fibroblast growth factor supports the survival of cerebral cortical neurons in primary culture. Proc Natl Acad Sci USA 83:7537–7541
Otto D, Frotscher M, Unsicker K (1989) Basic fibroblast growth factor and nerve growth factor administered in gel foam rescue medial septal neurons after fimbria fornix transection. J Neurosci Res 22:83–91
Ramirez JJ, Fass B, Kilfoil T, Henschel B, Grones W, Karpiak SE (1987) Ganglioside-induced enhancement of behavioral recovery after bilateral lesions of the entorhinal cortex. Brain Res 414:85–90
Skaper SD, Facci L, Leon A (1990) Ganglioside attenuates the delayed neurotoxicity of aspartic acid in vitro. Neurosci Lett 117:154–159
Skaper SD, Leon A, Facci L (1993) Basic fibroblast growth factor modulates sensitivity of cultured hippocampul pyramidal neurons to glutamate cytotoxicity: interaction with ganglioside GM1. Dev Brain Res 71:1–8
Sofroniew MV, Pearson RC, Cuello AC, Tagari PC, Stephens PH (1986) Parenterally administered GM1 ganglioside prevents retrograde degeneration of cholinergic cells of the rat basal forebrain. Brain Res 398:393–396
Stephens PH, Tagari PC, Garofalo L, Maysinger D, Piotte M, Cuello AC (1987) Neural plasticity of basal forebrain cholinergic neurons: effects of gangliosides. Neurosci Lett 80:80–84
Walicke PA, Cowan WM, Ueno N, Baird A, Guillemin R (1986) Fibroblast growth factor promotes survival of dissociated hippocampal neurons and enhances neurite extention. Proc Natl Acad Sci USA 83:3012–3016
Walsh TJ, Emerich DF, Schmechel DE (1989) GM1 ganglioside attenuates the behavioral deficits but not granule cell damage produced by intradentate colchicine. Brain Res 478:24–33
Yoshida K, Gage FH (1991) Fibroblast growth factors stimulate nerve growth factor synthesis and secretion by astrocytes. Brain Res 538:118–126
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Iwashita, A., Hisajima, H., Notsu, Y. et al. Effects of basic fibroblast growth factor and ganglioside GM1 on neuronal survival in primary cultures and on eight-arm radial maze task in adult rats following partial fimbria transections. Naunyn-Schmiedeberg's Arch Pharmacol 353, 342–348 (1996). https://doi.org/10.1007/BF00168638
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00168638