Počet záznamů: 1
Cholesterol modulates presynaptic and postsynaptic properties of excitatory synaptic transmission
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SYSNO ASEP 0531929 Druh ASEP J - Článek v odborném periodiku Zařazení RIV J - Článek v odborném periodiku Poddruh J Článek ve WOS Název Cholesterol modulates presynaptic and postsynaptic properties of excitatory synaptic transmission Tvůrce(i) Kořínek, Miloslav (FGU-C) RID, ORCID
González-González, I. M. (GB)
Smejkalová, Tereza (FGU-C) RID, ORCID
Hajduković, Dragana (FGU-C)
Skřenková, Kristýna (FGU-C) ORCID, RID
Krůšek, Jan (FGU-C) RID, ORCID
Horák, Martin (FGU-C) RID, ORCID
Vyklický ml., Ladislav (FGU-C) RID, ORCID, SAIČíslo článku 12651 Zdroj.dok. Scientific Reports. - : Nature Publishing Group - ISSN 2045-2322
Roč. 10, č. 1 (2020)Poč.str. 18 s. Jazyk dok. eng - angličtina Země vyd. GB - Velká Británie Klíč. slova synaptic transmission ; cholesterol ; NMDA receptor ; NMDA receptor ; neuroprotection ; synapse ; membrane Vědní obor RIV FH - Neurologie, neurochirurgie, neurovědy Obor OECD Neurosciences (including psychophysiology CEP GA17-02300S GA ČR - Grantová agentura ČR GJ16-03913Y GA ČR - Grantová agentura ČR TN01000013 GA TA ČR - Technologická agentura ČR LQ1604 GA MŠMT - Ministerstvo školství, mládeže a tělovýchovy Způsob publikování Open access Institucionální podpora FGU-C - RVO:67985823 UT WOS 000556400100041 EID SCOPUS 85088649214 DOI https://doi.org/10.1038/s41598-020-69454-5 Anotace Cholesterol is a structural component of cellular membranes particularly enriched in synapses but its role in synaptic transmission remains poorly understood. We used rat hippocampal cultures and their acute cholesterol depletion by methyl-beta-cyclodextrin as a tool to describe the physiological role of cholesterol in glutamatergic synaptic transmission. Cholesterol proved to be a key molecule for the function of synapses as its depletion resulted in a significant reduction of both NMDA receptor (NMDAR) and AMPA/kainate receptor-mediated evoked excitatory postsynaptic currents (eEPSCs), by 94% and 72%, respectively. We identified two presynaptic and two postsynaptic steps of synaptic transmission which are modulated by cholesterol and explain together the above-mentioned reduction of eEPSCs. In the postsynapse, we show that physiological levels of cholesterol are important for maintaining the normal probability of opening of NMDARs and for keeping NMDARs localized in synapses. In the presynapse, our results favour the hypothesis of a role of cholesterol in the propagation of axonal action potentials. Finally, cholesterol is a negative modulator of spontaneous presynaptic glutamate release. Our study identifies cholesterol as an important endogenous regulator of synaptic transmission and provides insight into molecular mechanisms underlying the neurological manifestation of diseases associated with impaired cholesterol synthesis or decomposition. Pracoviště Fyziologický ústav Kontakt Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Rok sběru 2021 Elektronická adresa https://www.nature.com/articles/s41598-020-69454-5
Počet záznamů: 1