Derivatives of ganglioside GM1 as neuronotrophic agents: comparison of in vivo and in vitro effects

Michael S. Cannella, Barbara Oderfeld-Nowak, Matgorzata Gradkowska, Matgorzata Skup, Lorella Garofalo, A. Claudio Cuello, Robert W. Ledeen

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Exogenously administered gangliosides have been shown to behave as neuronotrophic/neuritogenic agents in a variety of cell culture systems and animal models, but it is not known whether they operate by the same mechanism in vivo and in vitro. To probe this question we have employed two derivatives of GM1 lacking the negative charge: the methyl ester (GM1-CH3) and the NaBH4 reduction product of the latter (GM1-OH) in which the carboxyl group is replaced by a primary alcohol. Both derivatives proved to be as neuritogenic as GM1 in 3 cell culture systems: neuro-2A cels, PC12 cells and explanted dorsal root ganglia. However, GM1-OH proved ineffective when applied to two animal models involving reduction of cholinergic markers in: (a) hippocampus following lesion of the lateral fimbria and (b) nucleus basalis magnocellularis following cortical lesion; GM1-CH3 showed marginal activity in (a) but more in (b), possibly owing to slow hydrolysis to GM1 which was highly active in both animal models. These results indicate the necessity of a negative charge on the ganglioside molecule for in vivo but not in vitro activity and point to different mechanisms for the trophic effects of exogenous gangliosides.

Original languageEnglish (US)
Pages (from-to)286-294
Number of pages9
JournalBrain research
Volume513
Issue number2
DOIs
StatePublished - Apr 16 1990
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Keywords

  • Dorsal root ganglia
  • GM1 derivative
  • GM1 ganglioside
  • Neuro-2A cell
  • Nucleus basalis magnocellularis-cortex animal model
  • PC12 cell
  • Septohippocampal animal model

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