ISSN:
1573-4986
Keywords:
sialylcholesterol
;
synaptosomes
;
acetylcholine
;
choline uptake
;
calcium ions
Source:
Springer Online Journal Archives 1860-2000
Topics:
Chemistry and Pharmacology
Notes:
Abstract The effects of sialylcholesterol, a synthetic ganglioside analogue, on cholinergic synaptic functions were investigated using synaptosomes prepared from C57BL/6 mouse brain cortices. Addition of α-sialylcholesterol stimulated high K (50mm)-evoked acetylcholine (ACh) release from synaptosomes at concentrations ranging from 1 to 5 µm. The β-anomer of the sialyl compound also increased the neurotransmitter release at 5 µm, but the effect was much smaller than that of the α-anomer. Beta-sialylcholesterol appeared to increase high-affinity choline uptake and ACh synthesis, resulting in an increment in the release of ACh. On the other hand, α-sialylcholesterol did not change the synthetic rate of ACh, and instead it increased the depolarization-induced influx of calcium ions into synaptosomes, while the β-anomer did not affect the divalent cation influx. The enhanced calcium influx is thought to increase ACh release from synaptosomes treated with α-sialylcholesterol. These results imply that the two anomers of sialylcholesterol may modulate the synaptic membrane machinery differently, that is, the α-anomer may activate voltage-dependent calcium channels and the β-anomer may facilitate high-affinity choline uptake. In order to evaluate the ameliorating effect of sialylcholesterol, α-sialylcholesterol was applied to the synaptosomes from aged mice (34 months old), which have been shown to have a decreased ACh release (Tanakaet al., 1995,J Neurosci Res, in press [1]). The reduced neurotransmitter release recovered to the levels of younger animals, suggesting that sialylcholesterol might have a potential therapeutic use for restoring synaptic function that occurs in aged brains.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00731507
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