Effects of glucosylceramide synthase inhibitor and ganglioside GQ1b on synchronous oscillations of intracellular Ca2+ in cultured cortical neurons.
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.
Mizutani
A
A
Seikagaku Corporation, Tokyo Research Institute, Tokyo, Japan.
Kuroda
Y
Y
Muramoto
K
K
Kobayashi
K
K
Yamagishi
K
K
Inokuchi
J
J
D000818:Animals; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005333:Fetus; D005732:Gangliosides / Q000494:pharmacology*; D005964:Glucosyltransferases / Q000037:antagonists & inhibitors*; D006028:Glycosphingolipids / Q000502:physiology; D007700:Kinetics; D009025:Morpholines / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009991:Oscillometry; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D005732:Gangliosides; D006028:Glycosphingolipids; D009025:Morpholines; C039129:GQ1b ganglioside; C033110:RV 538; D005964:Glucosyltransferases; C023246:ceramide glucosyltransferase