Effects of gangliosides on the expression of autoimmune demyelination in the peripheral nervous system.
To test whether gangliosides (GA) might exert neuritogenic effects in vivo, experimental allergic neuritis (EAN) was studied clinically, neuropathologically, and immunologically in Lewis rats immunized with bovine peripheral nerve, P2 myelin protein, P2 myelin protein plus two different doses of GA, P2 with galactocerebroside (GC), and GA alone, each emulsified in adjuvant. All except the GA-treated group developed signs of EAN between days 11 and 14 after the injection. Rats immunized with P2 alone were the most severely affected. Rats given P2 plus GA and those given P2 plus GC displayed a significantly lower clinical score. Histological analysis revealed a comparable degree of inflammation of the peripheral nervous system and demyelination in the spinal nerve roots of bovine peripheral nerve- and P2-immunized rats. The P2 plus GA and P2 plus GC groups revealed similar degrees of pathology in the spinal nerve roots but the latter group stood apart from the rest in that it showed widespread peripheral nervous system changes extending distally into the sciatic nerve. Serological analysis demonstrated that P2 and GC, but not GA, elicited antibody (IgG) responses, but there was no correlation between antibody titer and clinical or histological involvement. The present data fail to support an enhancing role for gangliosides in the expression of EAN and, by extrapolation, in the Guillain-Barré syndrome, for which EAN serves as the laboratory model, and in which suggestions have been made that antibodies to GA may have pathogenetic significance.
Ponzin
D
D
Department of Neuropathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Menegus
A M
AM
Kirschner
G
G
Nunzi
M G
MG
Fiori
M G
MG
Raine
C S
CS
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000473:pathology*; D002417:Cattle; D005699:Galactosylceramides / Q000494:pharmacology; D005732:Gangliosides / Q000494:pharmacology*; D008297:Male; D004676:Myelin Basic Protein / Q000494:pharmacology; D018996:Myelin P2 Protein; D009444:Neuritis, Autoimmune, Experimental / Q000473:pathology*; D051381:Rats; D011917:Rats, Inbred Lew / Q000276:immunology; D012584:Sciatic Nerve / Q000276:immunology / Q000473:pathology
D001323:Autoantibodies; D005699:Galactosylceramides; D005732:Gangliosides; D004676:Myelin Basic Protein; D018996:Myelin P2 Protein; C002454:galactocerebroside