Ganglioside enhancement of neuronal differentiation, plasticity, and repair.

Abstract

Gangliosides are carbohydrate-rich complex lipids of large size and great complexity which are found in cell membranes, especially neuronal cell membranes. They are present in the external leaflet of the membrane. The hydrophobic moiety, consisting of sphingosine and fatty acid (stearic acid, 95%), is inserted into the membrane, while the hydrophilic moiety, consisting of sialic acid (NANA) and other carbohydrates, protrudes towards the extracellular fluid. Although gangliosides were discovered some 50 years ago, their potential role in neuronal functions has been appreciated only recently. During development, their composition and concentration change in a variety of animal species. Their role is indicated from studies which have shown that abnormalities in ganglioside metabolism can have a severe impairing effect on normal development. The mouse mutant weaver is characterized by cerebellar granule cell death, which is correlated by the lack of GM1 expression on the neuronal surface. On the other hand, inborn metabolic errors causing ganglioside accumulation in neurons (GM1 gangliosides) are correlated to an aberrant neurite outgrowth. A further appreciation of ganglioside action has been obtained either by adding gangliosides to neurons in culture or by treating animals during neuronal regeneration. It was found that these agents increased the rate and extent of sprouting of regenerating axons and enhanced neuronal differentiation and sprouting in vitro. Such effects were dependent upon the presence of the growth factor in the bathing medium; ganglioside incorporation, however, did not alter nerve growth factor (NGF) binding and internalization, indicating that some membrane events triggered by ganglioside incorporation may be relevant in neuronal differentiation and sprouting. More recently, we have obtained evidence showing that neurons from animals treated with gangliosides are more resistant to anoxia and ionic unbalances. It seems that ganglioside treatment prevents the decay of some key enzyme activity, such as Na+-K+-ATPase occurring after trauma. Indeed, the recent literature suggests that gangliosides may play an important role during development and, when injected into animals, enhance reparatory events in the central and peripheral nervous system.