New Evidence for the Morphofunctional Recovery of Striatal Function by Ganglioside GM1 Treatment Following a Partial Hemitransection of Rats. Studies on Dopamine Neurons and Protein Phosphorylation

  • Kjell Fuxe
  • Luigi F. Agnati
  • Fabio Benfenati
  • Isabella Zini
  • G. Gavioli
  • G. Toffano
Part of the FIDIA Research Series book series (FIDIA, volume 6)


In previous studies it has been shown that chronic treatment with GM1 can increase the survival of dopamine (DA) cell bodies with their dendrites in substantia nigra following a partial unilateral hemitransection of rats (Agnati et al., 1983a; 1984; Fuxe and Agnati, 1984; Toffano et al., 1983; 1984a). This in turn may be responsible for the enhancement of collateral sprouting observed from remaining striatal DA nerve terminals, leading to recovery of dopaminergic synaptic function in the striatum. This action has been found to be specific and not related to antiinflammatory effects of ganglioside GM1, since neither treatment with dexamethazone nor treatment with acetylsalicylic acid has been able to produce any trophic action on the nigral DA nerve cell bodies following a partial hemitransection in rats (Agnati et al., 1984). Recently we have also analyzed the effects of ganglioside GM1 treatment in unilateral partially hemitransected rats on striatal energy metabolism using the radioactive deoxyglycose technique and on striatal blood flow using radiolabelled iodoantipyrine as tracer (Agnati et al., 1985a). The results showed that GM1 can counteract the imbalance in striatal energy metabolism and in striatal blood flow found between the striatum of the lesioned and unlesioned side. This action may be related to excitatory effects of GM1 on the lesioned side and to inhibitory effects of GM1 on the unlesioned side. These results underline the evidence obtained in previous functional studies indicating that the metabolism of a striatum undergoing degenerative and regenerative changes can be at least partially restored following chronic GM1 treatment (Agnati et al., 1985a).


Ventral Tegmental Area Nerve Cell Body Lesion Side Intact Side Tyrosine Hydroxylase Inhibition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.





αmethyl-p-dl-tyrosine methyl ester

cyclic AMP

cyclic adenylic acid


sodium dodecyl sulphate CCK


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Agnati LF, Andersson K, Wiesel F, Fuxe K (1979) A method to determine dopamine levels and turnover rate in discrete dopamine nerve terminal systems by quantitative use of dopamine fluorescence obtained by Falck-Hillarp methodology. J Neurosci Methods 1: 365–373.PubMedCrossRefGoogle Scholar
  2. Agnati LF, Fuxe K, Calza L, Benfenati F, Cavicchioli L, Toffano G, Goldstein M (1983a) Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting. Acta Physiol Scand 119: 347–363.PubMedCrossRefGoogle Scholar
  3. Agnati LF, Benfenati F, Battistini N, Caviocchioli L, Fuxe K, Toffano G (1983b) Selective modulation of 3H-spiperone labelled 5-HT receptors by subchronic treatment with the ganglioside GM1 in the rat. Acta Physiol Scand 117: 311–314.PubMedCrossRefGoogle Scholar
  4. Agnati LF, Fuxe K, Benfenati F, Battistini N, Zini I, Toffano G (1983c) Chronic ganglioside treatment counteracts the biochemical signs of dopamine receptor supersensitivity induced by chronic haloperidol treatment. Neurosci Lett 40: 293–297.PubMedCrossRefGoogle Scholar
  5. Agnati LF, Fuxe K, Toffano G, Calza L, Benfenati B, Zini I, Battistini N, Goldstein M, Zoli M (1984) Evidence for structural plasticity in the nigrostriatal dopamine neurons: Morphometrical and biochemical evidence for a trophic action of gangliosides on partially lesioned nigrostriatal dopamine neurons. In: Racagni G, Paoletti R, Kielholz P (eds): Clinical Neuropharmacology, Vol 7, Suppl 1. Raven Press, pp. 594–595.Google Scholar
  6. Agnati LF, Fuxe K, Benfenati F, Zoli M, Owman C, Diemer NH, Kâhrström J, Toffano G, Cimino M (1985) Effects of Ganglioside GM1 treatment on striatal glucose metabolism, blood flow, and protein phosphorylation of the rat. Acta Physiol Scand 125: 43–53.PubMedCrossRefGoogle Scholar
  7. Agnati LF, Fuxe K, Davalli P, Corti A, Zini I, Merlo Pich E, Zoli M, Gavioli J (1986) Studies on the involvement of polyamines for the trophic actions of the ganglioside GM1 in mechanically and 6-hydroxydopamine lesioned rats. Evidence for â permissive role of putrescine, this volume.Google Scholar
  8. Andersson K, Fuxe K, Agnati LF (1985) Determinations of catecholamine half-lives and turnover rates in discrete catecholamine nerve terminal systems of the hypothalamus, the preoptic region and the forebrain by quantitative histofluorimetry. Acta Physiol Scand 123: 411–426.PubMedCrossRefGoogle Scholar
  9. Consolazione A, Aldinio C, Agnati LF, Fuxe K, Savoini G, Toffano G (1985) Experimental conditions in which GM1 is or not able to facilitate functional recovery following injury of adult mammalian brain. In: ISN Satellite Symposium on Neuronal plasticity and gangliosides, Mantova, Italy, Poster Abstract P9.Google Scholar
  10. Cuello AC, Stephens PH, Sofroniew MV, Pearson RCA, Tagari P, Powell TPS (1985) Effects of gangliosides on cholinergic neurones of the nucleus basalis following unilateral cortical lesions. In: ISN Satellite Symposium on Neuronal Plasticity and Gangliosides, Mantova, Italy, Abstract 38.Google Scholar
  11. Facci L, Leon A, Toffano G, Sonnino S, Ghidoni R, Tettamanti G (1984) Promotion of neuritogenesis in mouse neuroblastoma cells by exogenous gangliosides. Relationship between the effect and the cell association of ganglioside GM1. J Neurochem 42: 299–305.PubMedCrossRefGoogle Scholar
  12. Fuxe K, Agnati LF (1984) Gangliosides as regulatory factors in central catecholamine neurons. In: Magistretti PJ, Morrison JH, Bloom FE (eds): Discussions in Neurosciences. Nervous system development and repair. FESN, Vol. 1, No. 2, pp. 84–89.Google Scholar
  13. Ghidoni R, Venerando B, Fiorilli A, Tettamanti G (1985) Metabolism of exogeneously administered gangliosides and related glycolipids in the rat. In: ISN Satellite Symposium on Neuronal Plasticity and Gangliosides, Mantova, Italy, Abstract 11.Google Scholar
  14. Gorio A, Di Gregorio F, Janigro D, Milan F, Vitadello M, Bianci R (1985) Gangliosides have a decay preventing activity on neuronal membrane functions. In: ISN Satellite Symposium on Neuronal Plasticity and Gangliosides, Mantova, Italy, Abstract 27.Google Scholar
  15. Karpiak SE, Li YS, Aceto P, Mahadik SP (1986) Acute effects of gangliosides on CNS injury, this volume.Google Scholar
  16. Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacterophage T4. Nature 227: 680–685.PubMedCrossRefGoogle Scholar
  17. Leon A, Benvegnu D, Dai Toso R, Presti D, Facci L, Giorgi O, Toffano G (1984) Dorsal root ganglia and nerve growth factor: a model for understanding the mechanism of GM1 effects on neuronal repair. J. Neurosci Res 12: 277–287.PubMedCrossRefGoogle Scholar
  18. Nagai Y, Tsuji S, Nakajima J, Sasaki T (1986) Functional analysis of ganglioside-respondable human neuroblastoma cell lines, this volume.Google Scholar
  19. Nestlér Greengard P (1983) Protein phosphorylation in the brain. Nature 305: 583–588.Google Scholar
  20. Sachs C, Champlain J, Malmfors T, Olson L (1970) The postnatal development of noradrenaline uptake in the adrenergic nerves of different tissues from the rat. Eur J Pharmacol 9: 67–79.PubMedCrossRefGoogle Scholar
  21. Toffano G, Savoini G, Moroni F, Lombardi G, Calza L, Agnati LF (1983) GM1 ganglioside stimulates the regeneration of dopaminergic neurons in the central nervous system. Brain Res 261: 163–166.PubMedCrossRefGoogle Scholar
  22. Toffano G, Savoini G, Aldinio C, Valenti G, Dal Toso R, Leon A, Calza L, Zini I, Agnati LF, Fuxe K (1984a) Effects of gangliosides on the functional recovery of damaged brain. In: Ledeen RW, Yu RK, Rapport MM, Suzuki K, Tettamanti G (eds): Ganglioside structure, function and biomedical potential. Plenum Press, New York, in press.Google Scholar
  23. Toffano G, Agnati LF, Fuxe K, Aldinio C, Consolazione A, Valenti G, Savoini G (1984b) Effects of GM1 ganglioside treatment on the recovery of dopaminergic nigro-striatal neurons after different types of lesion. Acta Physiol Scand 122: 313–321.PubMedCrossRefGoogle Scholar
  24. Tsuji S, Nakajima J, Sasaki T, Nagai Y (1985) Bioactive gangliosides. IV. Ganglioside GQ1b/Ca2+dependent protein kinase activity exists in the plasma membrane fraction of neuroblàstoma cell line, GOTO. J Biochem 97: 969–972.PubMedGoogle Scholar
  25. Varon S, Skaper SD, Katoh-Semba R (1986) Neuritic responses to GM1 ganglioside in several in vitro systems, this volume.Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1986

Authors and Affiliations

  • Kjell Fuxe
    • 1
  • Luigi F. Agnati
    • 2
  • Fabio Benfenati
    • 2
  • Isabella Zini
    • 2
  • G. Gavioli
    • 2
  • G. Toffano
    • 3
  1. 1.Department of HistologyKarolinska InstitutetStockholmSweden
  2. 2.Department of Human PhysiologyUniversity of ModenaModenaItaly
  3. 3.Fidia Research LaboratoriesAbano Terme, PadovaItaly

Personalised recommendations