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Effects of glucosylceramide synthase inhibitor and ganglioside GQ1b on synchronous oscillations of intracellular Ca2+ in cultured cortical neurons

Mizutani, A.; Kuroda, Y.; Muramoto, K.; Kobayashi, K.; Yamagishi, K.; Inokuchi, J.

Biochemical and Biophysical Research Communications 222(2): 494-498

1996

ISSN/ISBN: 0006-291X
PMID: 8670233
Document Number: 459815
To evaluate the role of endogenous gangliosides in synapse formation, the glucosylceramide synthase inhibitor, D-threo-1-phenyl-2-decanoylamino-3-morpholino-1-propanol (D-PDMP), was used to deplete glycosphingolipids (GSLs) of cultured rat cerebral cortical neurons. Synapse formation between the neurons was estimated by the synchronous oscillation of synaptic activity monitored by fura-2 calcium imaging. Treatment with D-PDMP resulted in dose- and time-dependent decreases in the frequency of synchronous oscillations. When a series of gangliosides (GM3, GM1, GD3, GD1b, GT1b, and GQ1b) was supplemented to the GSL depleted cells, only GQ1b was able to normalize the decreased frequency by D-PDMP. These results suggest that de novo synthesis of a particular molecular species of the gangliosides, GQ1b, is essential for synapse formation and synaptic activity.

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