Sensory nerve-dominant nerve degeneration and remodeling in the mutant mice lacking complex gangliosides

Gangliosides, sialic acid-containing glycosphingo-lipids, are enriched in the mammalian nervous system. Since mutant mice with disrupted beta1,4-N-acetylgalactosaminyl-transferase (GM2/GD2 synthase) were generated, there have been several studies on the pathology of the mutant mice, i.e. mild functional disorders and Wallerian degeneration in the peripheral nervous system. To further analyze the chronological alteration in the mutant mice, we examined the peripheral and CNS mainly with morphological approaches, such as electron microscopy and immunohistochemistry. Accordingly with the sensory dysfunction, neural degeneration, glial proliferation and synaptic remodeling in the dorsal horn of the spinal cord were found in adult mice. Thick astrocytic processes with densely packed glial filaments were extended among the neuropils and around blood vessels. Morphological changes in the synaptic vesicles and modes of synaptic contacts with central terminals were detected, suggesting synaptic remodeling following the degeneration. These results suggest that complex gangliosides are essential in the maintenance of integrity in architecture and function of the nervous system, lack of which results in neural degeneration in a sensory nerve-dominant manner.