GANGLIOSIDE SYNTHESIS DURING THE DEVELOPMENT OF NEURONAL POLARITY - MAJOR CHANGES OCCUR DURING AXONOGENESIS AND AXON ELONGATION, BUT NOT DURING DENDRITE GROWTH OR SYNAPTOGENESIS

Changes in the levels and types of gangliosides occur during neuronal differentiation and development, but no studies have correlated these changes with defined events in neuronal morphogenesis. Here, we have a nalyzed the relationship between ganglioside synthesis and the develop ment of axons and dendrites in polarized neurons, using hippocampal ne urons cultured in such a way that axons and dendrites are generated by a defined sequence of events and in which there is virtu ally no cont amination by glial cells, Neurons were la beled with [4,5-H-3]dihydros phingosine, which was rapidly incorporated into cells and metabolized to H-3-labeled glycosphingolipids, The rate of H-3-labeled glycosphing olipid synthesis was directly proportional to the initial rate of [4,5 -H-3]dihydrosphingosilae uptake and was linear versus time for up to 9 h of incubation, The major changes in H-3-labeled ganglioside synthes is occurred during the period of axonogenesis and rapid axon growth, D uring axonogenesis, there was a significant increase in the synthesis of complex gangliosides (i.e. G(m1), G(D1a), G(D1b), and G(T1b)) with a corresponding reduction in the synthesis of glucosylceramide and gan glioside G(D3). During the stage of rapid axon growth, the ratio of a- to b-series gangliosides increased significantly, However, during den dritogenesis, dendrite growth, and synaptogenesis, there was little ch ange in ganglioside synthesis, with a small and gradual increase in th e ratio of a- to b-series gangliosides and an increase in the synthesi s of gangliosides G(D1a) and G(T1b). These results indicate that despi te major changes in neuronal morphology and functionality as neurons m ature, changes in ganglioside synthesis are restricted to early stages of neuronal development, namely axonogenesis and rapid axon elongatio n.