Gangliosides in the nervous system during development and regeneration.

Abstract

Gangliosides are present in nervous tissues of echinoderms and chordates, but the amounts and patterns differ widely. There are changes in the ganglioside contents of nervous tissues during development in most animals studied. To a large extent, regional differences and changes with development and degeneration in ganglioside composition reflect changing and different proportions of cellular types and subcellular organelles within the tissue. GM1 and GM4 are enriched in myelin; GD1a may be a marker for dendritic arborization. During regeneration of fish optic nerve and rat sciatic nerve there is an increased amount of ganglioside proximal to the regenerating axon tips, which may largely be a result of accumulation. This could provide a relatively large reservoir of ganglioside to become incorporated into the sprouting axolemma. Gangliosides added exogenously to growth medium can induce neuritogenesis of several types of neurons. The mechanisms of this action are unknown but may be related to nerve growth factor, microskeletal organization, membrane fluidity, and other factors. Gangliosides injected into young animals affect brain development, but further studies are required to determine these effects more specifically. Ganglioside administration increases the number of sprouts in regenerating peripheral nerves, but does not seem to accelerate axonal elongation. Parenterally administered gangliosides alter the recovery of brain tissue from a variety of types of lesions, and clinical trials are in progress to determine if they are of benefit in human neurological disorders. The biochemical mechanisms of these in vivo ganglioside effects are poorly understood, but may involve modulation of several enzyme systems as well as other properties of neural membranes, such as fluidity. It is possible that gangliosides may play similar roles and operate through some of the same mechanisms in developing and regenerating nervous tissues.