Gangliosides increase the survival of lesioned nigral dopamine neurons and favour the recovery of dopaminergic synaptic function in striatum of rats by collateral sprouting.
The effects of chronic ganglioside treatment GM-1 (10 mg/kg, i.p., once daily for 56 days) have been evaluated on the degenerative and regenerative features of nigrostriatal dopamine (DA) neurons following a partial lesion by tyrosine hydroxylase immunocytochemistry in combination with morphometrical analysis and by quantitative DA receptor autoradiography. Chronic GM-1 treatment resulted in the maintenance in the number of DA cell bodies, terminals and striatal area on the lesioned side and also increased dendrite length of the DA nerve cells in the zona reticulata on that side. The lesion induced DA receptor supersensitivity was counteracted by chronic treatment with GM-1 and the apomorphine induced rotational behaviour was significantly reduced. The hypothesis is introduced that following ganglioside treatment some lesioned DA nerve cells do not degenerate, but elongate their dendrites to give increased trophic support to DA cell bodies with intact DA axons. These increased dendro-dendritic interactions may enable the unlesioned DA cells to increase the density of their striatal nerve terminal networks via collateral sprouting leading to recovery of dopaminergic synaptic function as evidenced in the receptor autoradiographical and behavioural analysis. Gangliosides may therefore possibly represent a new type of drug in the treatment of Parkinson's disease and aging processes in DA systems.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003712:Dendrites / Q000187:drug effects; D005677:G(M1) Ganglioside / Q000494:pharmacology*; D005732:Gangliosides / Q000494:pharmacology*; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects; D009411:Nerve Endings / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013134:Spiperone / Q000378:metabolism; D013378:Substantia Nigra / Q000166:cytology*; D013569:Synapses / Q000187:drug effects*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D005732:Gangliosides; D011954:Receptors, Dopamine; D005677:G(M1) Ganglioside; D013134:Spiperone; D014446:Tyrosine 3-Monooxygenase