Monosialoganglioside internal ester stimulates the dopaminergic reinnervation of the striatum after unilateral...

The effects of the administration of GM1 monosialoganglioside internal ester, AGF2, on the dopaminergic reinnervation of the striatum in rats with unilateral hemitransection has been studied. AGF2 increases the apparent Vmax and the density of tyrosine-hydroxylase-positive nerve terminals in the striatum of the lesioned side, without modification of the tyrosine-hydroxylase activity in the unlesioned side. AGF2, at lower doses, is more active than its parent natural molecule GM1. AGF2 has a larger half-life and a higher distribution volume than GM1, and undergoes a slow hydrolysis in the serum releasing the original natural compound GM1. Mannitol and dexamethazone, often used to prevent swelling of the brain after injury, or isoaxonine, proposed to stimulate neurite growth are unable to reproduce the effects of AGF2 on the recovery of striatal tyrosine-hydroxylase activity after hemitransection. The data are compatible with the view that AGF2, through its conversion into GM1, facilitates the collateral sprouting of the nigro-striatal dopaminergic neurons.