Cholesterol-dependent balance between evoked and spontaneous synaptic vesicle recycling
| Autor: | Ege T. Kavalali, Xinran Liu, Mert Ertunc, Catherine R. Wasser |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
medicine.medical_specialty
Physiology Cholesterol Vesicle Neurotransmission Hippocampal formation Biology Synaptic vesicle Horseradish peroxidase chemistry.chemical_compound Mevastatin Endocrinology chemistry Internal medicine medicine biology.protein Synaptic vesicle recycling lipids (amino acids peptides and proteins) medicine.drug |
| Zdroj: | The Journal of Physiology. 579:413-429 |
| ISSN: | 0022-3751 |
| Popis: | Cholesterol is a prominent component of nerve terminals. To examine cholesterol's role in central neurotransmission, we treated hippocampal cultures with methyl-β-cyclodextrin, which reversibly binds cholesterol, or mevastatin, an inhibitor of cholesterol biosynthesis, to deplete cholesterol. We also used hippocampal cultures from Niemann-Pick type C1-deficient mice defective in intracellular cholesterol trafficking. These conditions revealed an augmentation in spontaneous neurotransmission detected electrically and an increase in spontaneous vesicle endocytosis judged by horseradish peroxidase uptake after cholesterol depletion by methyl-β-cyclodextrin. In contrast, responses evoked by action potentials and hypertonicity were severely impaired after the same treatments. The increase in spontaneous vesicle recycling and the decrease in evoked neurotransmission were reversible upon cholesterol addition. Cholesterol removal did not impact on the low level of evoked neurotransmission seen in the absence of synaptic vesicle SNARE protein synaptobrevin-2 whereas the increase in spontaneous fusion remained. These results suggest that synaptic cholesterol balances evoked and spontaneous neurotransmission by hindering spontaneous synaptic vesicle turnover and sustaining evoked exo-endocytosis. |
| Databáze: | OpenAIRE |
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