Lewis rats immunized with GM1 ganglioside do not develop peripheral neuropathy

Abstract

Elevated levels of anti-GM1 antibodies are associated with motor nerve syndromes. Although there is a lot of circumstantial evidence that anti-GM1 antibodies may be causing the disease, their precise role remains unclear. In order to study the role of anti-GM1 antibodies in the pathogenesis of peripheral neuropathy, eight Lewis rats were injected with GM1 ganglioside mixed with keyhole limpet hemocyanin (KLH) and emulsified with Freund's adjuvant and three rats were immunized with GM1 in liposomes. Although IgM class anti-GM1 antibodies were detected in all animals immunized with GM1, none of the animals exhibited overt signs of neuropathy during 6 months after initial immunization. IgG antibody to GM1 was not produced in any of the animals. There was no pathological evidence of nerve damage. These studies suggest that elevated levels of IgM anti-GM1 antibodies by themselves do not cause nerve damage in rats.

Fig. 1

Binding of rat antibodies to gangliosides. In panels A-C, lane 1 contained bovine brain ganglioside standards (10 μg) and lane 2 contained purified GM1 (2 μg). Panel A depicts orcinol stained glycolipids. The other panels were immunostained with 1:100 dilution of rat sera and peroxidase-conjugated goat anti-rat IgM (μ-chain specific). Test sera were from rat #3 (panel B) and rat #14 (panel C).

Fig. 2

One micrometer thick Spurr’s resin (epoxy), cut transversely through the sciatic nerve at middle part of thigh segment. (A) Normal sciatic nerve of rat as control. (B) Sciatic nerve of rat immunized with GM1. Both are toludine blue-stained (x 400).