Gangliosides potentiate in vivo and in vitro effects of nerve growth factor on central cholinergic neurons.
The effects of nerve growth factor beta (beta-NGF) and ganglioside GM1 on forebrain cholinergic neurons were examined in vivo and in vitro. Following unilateral decortication of rats, GM1 (5 mg/kg per day) administered intracerebroventricularly could protect forebrain cholinergic neurons of the nucleus basalis magnocellularis from retrograde degeneration in a manner comparable to beta-NGF. Administered in combination with beta-NGF, GM1 produced a significant increase in choline acetyltransferase activity in the nucleus basalis magnocellularis and remaining cortex ipsilateral to the lesion. Concentrations of GM1 that were ineffective when administered alone in this lesion model, when given with beta-NGF, potentiated beta-NGF effects in both of the above brain areas. In dissociated septal cells in vitro, an increase in choline acetyltransferase activity was noted at beta-NGF concentrations as low as 0.1 pM and reached a plateau at 1 nM. A moderate (up to 35%) stimulation of choline acetyltransferase activity was observed with 10 microM GM1. The application of beta-NGF in combination with 10 microM GM1 or 0.1 microM GM1, a concentration that is ineffective in these cultures, produced a much greater increase in choline acetyltransferase activity than did beta-NGF alone. These observations support the idea that exogenously applied gangliosides can elicit trophic responses in cholinergic neurons of the central nervous system. That GM1 increases and even potentiates beta-NGF effects suggests that some of the trophic actions of this compound may be mediated through endogenous trophic factors.
Cuello
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AC
Department of Pharmacology and Therapeutics, McGill University, Montreal, PQ, Canada.
Garofalo
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L
Kenigsberg
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RL
Maysinger
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D
D000818:Animals; D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D002794:Choline / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004027:Diencephalon / Q000166:cytology; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D051381:Rats; D011919:Rats, Inbred Strains; D013687:Telencephalon / Q000166:cytology
D009414:Nerve Growth Factors; D005677:G(M1) Ganglioside; D002795:Choline O-Acetyltransferase; D002794:Choline