ganglioside--gd1b and Nerve-Degeneration

The present study evaluated the neurotoxicity of various gangliosides against dopaminergic neurons in mesencephalic cultures. Among them, GD1a and GD1b but not GD3 and GQ1b were found to be neurotoxic against dopaminergic neurons as determined by TH immunocytochemistry and [(3)H]DA uptake. When quantified and expressed as a percentage of control values, treatment with 60-200 microg/ml GD1a and GD1b attenuated the number of TH-ip neurons by 31-47% and 37-55%, respectively, compared with non-treated control cultures. Consistent with the results of the TH immunocytochemistry, treatment with 60-200 microg/ml GD1a and GD1b reduced [(3)H]DA uptake levels by 27-56% and 41-60%, respectively, compared with non-treated control cultures. This neurotoxicity was almost completely abolished in the presence of neuraminidase, which removes the sialic acid residues from ganglioside, or in the treatment of insulin or IGF-1. Additional immunostaining also showed a significant loss of GABAergic neurons in GD1a or GD1b-treated cultures, indicating non-selective neurotoxicity of GD1a and GD1b. Moreover, these gangliosides had little effect on nitric oxide (NO) production in mesencephalic or microglia cultures. Together, these data suggest that GD1a and GD1b exert a direct neurotoxicity against dopaminergic neurons independent of NO and/or microglia.

Topics: Animals; Cell Death; Cells, Cultured; Dopamine; Gangliosides; Insulin; Insulin-Like Growth Factor I; Mesencephalon; Microglia; N-Acetylneuraminic Acid; Nerve Degeneration; Neuraminidase; Neurons; Nitric Oxide; Rats; Rats, Sprague-Dawley

Systemic infusion of high-titer anti-GD1b antiserum to two rabbits pre-inoculated with keyhole limpet hemocyanin and Freund's complete adjuvant was performed. The two rabbits had low-titer anti-GD1b antibody in sera. Although no apparent clinical signs were observed, pathological examinations showed vacuolar degeneration with macrophage infiltration in a few axons in the dorsal columns of the spinal cords from the two rabbits. No such pathological changes were observed in the other two pre-inoculated rabbits infused with normal rabbit sera. Anti-GD1b antibody therefore may cause degeneration in rabbit sensory neurons with central axons extending to the dorsal column.

Topics: Animals; Ataxia; Enzyme-Linked Immunosorbent Assay; Gangliosides; Immunization, Passive; Immunoglobulin G; Macrophages; Nerve Degeneration; Neurons, Afferent; Rabbits; Vacuoles