Gangliosides and Sialylcholesterol as Modulators of Synaptic Functions^a

Abstract

Gangliosides were shown to enhance the release of acetylcholine from synaptosomes on stimulation. The influx of calcium ion into synaptosomes on membrane depolarization was increased by gangliosides. This was hypothesized to be an underlying mechanisms for the enhancement of acetylcholine release. Studies using calcium channel blockers revealed that four distinct types of voltage-dependent calcium channels occurred in cerebrocortical synapses, and that the N-type was primarily responsible for the evoked release of acetylcholine. An additional result suggests that gangliosides may act mainly on the N-type calcium channel. Cholinergic-specific gangliosides, Chol-1 alpha, were assumed to participate in the mechanism of high-affinity choline uptake. These two different actions of gangliosides were found to be mimicked by synthetic ganglioside analogs. Calcium influx was increased by alpha-sialylcholesterol, and choline uptake was accelerated by beta-sialylcholesterol. Gangliosides and sialylcholesterol having these apparently beneficial effects were shown to ameliorate decreased functions of synapses from aged brains.

Neuromuscular synaptic function in mice lacking major subsets of gangliosides

“…However, we found no major synaptic deficits in both null-mutants. This is quite surprising, in view of studies suggesting a synaptic role for gangliosides on the basis of exogenous ganglioside application (Tanaka et al, 1997;Ando et al, 1998), as well as the reported co-localization in lipid rafts of gangliosides and proteins important for neuroexocytosis (Chamberlain et al, 2001;Lang et al, 2001;Taverna et al, 2004;Salaun et al, 2004). The only changes we observed were some extra degree of rundown of transmitter release at high intensity use at the dKO NMJ and a temperature-specific increase in quantal content at 35 C in GD3s-KO NMJs, compared to WT.…”

“…In the light of their known effects on ion-channels and their particular abundance in synaptic regions, gangliosides are thought to play a role in neurotransmitter release, which is critically dependent on presynaptic ion-channel function (Wieraszko and Seifert, 1985;Ramirez et al, 1990;Egorushkina et al, 1993;Takamiya et al, 1996;Tanaka et al, 1997;Furuse et al, 1998;Ando et al, 1998;Meir et al, 1999;Chiavegatto et al, 2000;Bullens et al, 2002;Hakomori, 2003;Proia, 2003). Several important proteins of the release machinery co-localize with gangliosides within lipid rafts (Chamberlain et al, 2001;Lang et al, 2001;Taverna et al, 2004;Salaun et al, 2004).…”

Ca²⁺ Channel Currents Inhibited by Serum from Select Patients with Guillain-Barré Syndrome

“…Some studies demonstrate a relationship between gangliosides and calcium channels. GM1 and GQ1b may be involved in the activation of calcium channels, including L-type and N-type calcium channels [12, 13, 24]. Based on the results of the present study, we suggest that anti-ganglioside antibodies in the serum of patients with GBS might influence calcium channel inhibition in PC12 cells.…”

Novel Ganglioside-mediated Entry of Botulinum Neurotoxin Serotype D into Neurons

“…Colocalization was evaluated by measuring the correlation coefficients (28) between HCR and either syp1 or Rab5 for eight independent fields; graphs represent the average with S.E. Scale bar ϭ 20 m. ***, p Ͻ 0.001. been shown (51), where vacuolar ATPase activation and intensity of synaptic response are modulated by gangliosides (52,53). Several groups estimate that gangliosides comprise only a minor component of the SV lipidome; likewise, SVs contain a limited number of molecules of SV2 (1-5 molecules) and synaptotagmin (7-15 molecules) that serve as protein receptors for several BoNT serotypes (54 -56).…”