Oxysterol modulates neurotransmission via liver-X receptor/NO synthase-dependent pathway at the mouse neuromuscular junctions.
Neuropharmacology
; 150: 70-79, 2019 05 15.
Article
em En
| MEDLINE
| ID: mdl-30898570
ABSTRACT
Elimination of brain cholesterol occurs in the form of 24S-hydroxycholesterol (24S-HCh) that may modulate physiological processes outside the brain. Here, using microelectrode recording of postsynaptic responses (end-plate potentials, EPPs) and fluorescent marker (FM1-43) for endo-exocytosis we studied the effects of prolonged application of 24S-HCh (2.5â¯h, 0.4⯵M) on the neurotransmission in the mice diaphragm. 24S-HCh enhanced the depression of EPP amplitude (indicator of neurotransmitter release) and suppressed the FM1-43 dye unloading from nerve terminals (indicator of exocytosis) during electrical nerve stimulation at 20â¯Hz, without affecting miniature EPP amplitude and frequency. Comparison of the rates of neurotransmitter and FM1-43 releases suggested an increase in time required for the synaptic vesicle reuse. Additionally, 24S-HCh potentiated an increase in DAF-FM fluorescence (a NO-sensitive marker) in response to 20â¯Hz stimulation. All effects of 24S-HCh were completely prevented by liver X receptor antagonist. Either inhibitors of NO synthases (TRIM, cavtratin) or protein synthesis blocker counteracted the 24S-HCh-mediated enhancement in DAF-FM fluorescence, while inhibition of NO production with l-NAME or cavtratin and extracellular NO chelation suppressed the effect of 24S-HCh on FM1-43 dye loss during 20â¯Hz activity. Pretreatment for 5 days with inhibitor of 24S-HCh synthesis (voriconazole) had opposite effects on the FM1-43 unloading and NO synthesis. These data suggest that prolonged exposure to 24S-HCh attenuates recruitment of synaptic vesicle to exocytosis during 20â¯Hz stimulation acting via liver Ð¥ receptor/NO-dependent signaling.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
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Transmissão Sináptica
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Óxido Nítrico Sintase
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Receptores X do Fígado
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Hidroxicolesteróis
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Junção Neuromuscular
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article