Gangliosides potentiate in vivo and in vitro effects of nerve growth factor on central cholinergic neurons.

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Abstract
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. Concentration of GM1 that were ineffective when administered alone in this lesions 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 concentration as low as 0.1 pM and reaced a plateau at 1 nM. A moderate (up to 35%) stimulation of choline acetyltransferase activity was observed with 10 .mu.M GM1. The application of .beta.-NGF in combination with 10 .mu.M GM1 or 0.1 .mu.M GM1, a concentration that is ineffective in these cultures, produced a much greater increase in choline acetyltransferase activity than did B-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 tropic actions of this compound may be mediated through endogenous trophic factors.