Kůdová, Hana* Dotaz Zobrazit nápovědu
- MeSH
- erytroplazie ultrastruktura MeSH
- lidé MeSH
- nádory hrtanu patologie MeSH
- Check Tag
- lidé MeSH
Neurosteroids are steroids synthesized de novo in the brain from cholesterol in an independent manner from peripheral steroid sources. The term "neuroactive steroid" includes all steroids independent of their origin, and newly synthesized analogs of neurosteroids that modify neuronal activities. In vivo application of neuroactive steroids induces potent anxiolytic, antidepressant, anticonvulsant, sedative, analgesic and amnesic effects, mainly through interaction with the γ-aminobutyric acid type-A receptor (GABAAR). However, neuroactive steroids also act as positive or negative allosteric regulators on several ligand-gated channels including N-methyl-d-aspartate receptors (NMDARs), nicotinic acetylcholine receptors (nAChRs) and ATP-gated purinergic P2X receptors. Seven different P2X subunits (P2X1-7) can assemble to form homotrimeric or heterotrimeric ion channels permeable for monovalent cations and calcium. Among them, P2X2, P2X4, and P2X7 are the most abundant within the brain and can be regulated by neurosteroids. Transmembrane domains are necessary for neurosteroid binding, however, no generic motif of amino acids can accurately predict the neurosteroid binding site for any of the ligand-gated ion channels including P2X. Here, we will review what is currently known about the modulation of rat and human P2X by neuroactive steroids and the possible structural determinants underlying neurosteroid-induced potentiation and inhibition of the P2X2 and P2X4 receptors. This article is part of the Special Issue on "Purinergic Signaling: 50 years".
- MeSH
- adenosintrifosfát metabolismus MeSH
- iontové kanály řízené ligandy * metabolismus MeSH
- krysa rodu rattus MeSH
- lidé MeSH
- mozek metabolismus MeSH
- neurosteroidy * MeSH
- purinergní receptory P2X metabolismus MeSH
- purinergní receptory P2X2 metabolismus MeSH
- vazebná místa MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Publikační typ
- abstrakt z konference MeSH
Předvakcinační a povakcinační vyšetření protilátek proti kmenům obsažených ve vakcínách pro sezónu 2021/2022 bylo zajištěno u 94 pacientů dialyzačních středisek. Hodnocení registrovaných vakcín potvrdilo jejich význam při prevenci chřipky u dialyzovaných.
Pre-vaccination and post-vaccination screening of antibodies against the strains included in the 2021/2022 vaccines was conducted in 94 dialysis patients. Evaluation of the authorized vaccines confirmed their high role in the prevention of influenza.
- MeSH
- antigeny klasifikace terapeutické užití MeSH
- chřipka lidská imunologie prevence a kontrola MeSH
- dialýza ledvin * MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- sérokonverze MeSH
- statistika jako téma MeSH
- vakcinace statistika a číselné údaje MeSH
- vakcíny proti chřipce * analýza klasifikace MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- zprávy MeSH
- Geografické názvy
- Česká republika MeSH
Pregnenolone sulfate (PS), an endogenously occurring neurosteroid, has been shown to modulate the activity of several neurotransmitter-gated channels, including the NMDA receptor (NMDAR). NMDARs are glutamate-gated ion channels involved in excitatory synaptic transmission, synaptic plasticity, and excitotoxicity. In this study, we analyzed the effects of PS on calcium signaling in cultured hippocampal neurons and HEK293 cells expressing NMDAR. The cells were loaded with the Ca(2+) sensor Fura-2. In agreement with previous electrophysiological experiments, PS potentiated the increases in intracellular Ca(2+) induced by an exogenous application of glutamate; however, PS also increased intracellular Ca(2+) in the absence of exogenous NMDA agonist. The agonist-independent effect of PS was induced in all neurons studied and in HEK293 cells expressing GluN1/GluN2A-B receptors in a neurosteroid-specific manner. We conclude that PS is an endogenous NMDA agonist that activates the GluN1/GluN2A-B receptors.
- MeSH
- gating iontového kanálu fyziologie MeSH
- HEK293 buňky MeSH
- lidé MeSH
- pregnenolon metabolismus MeSH
- receptory N-methyl-D-aspartátu metabolismus MeSH
- vápník metabolismus MeSH
- vápníková signalizace fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Postictal potentiation presented immediately after cortical seizures in immature rats might be due to imbalance between excitation and inhibition. The aim of the present study was to determine whether augmentation of inhibition mediated by GABAA receptors could also suppress the postictal potentiation. METHODS: Twelve-day old rats with implanted electrodes were used in our study. Five drugs were tested: the agonist muscimol, the positive modulator midazolam and three neurosteroids affecting GABAA receptors-allopregnanolone, pregnanolone sulphate and pregnanolone glutamate. RESULTS: None of the five drugs was able to suppress potentiation appearing immediately after cortical epileptic afterdischarges, but all of them exhibited delayed anticonvulsant action 10 (in the case of midazolam and muscimol) or 20 min (all three steroids) after cortical seizures. CONCLUSION: Our results support a role of GABA in augmentation of cortical after discharges after longer intervals, whereas immediate postictal potentiation is not affected by GABAergic drugs. Due to similar effect with GABAergic drugs, the main mechanism of action of the three steroids tested is potentiation of GABAergic inhibition.
- MeSH
- antikonvulziva farmakologie MeSH
- časové faktory MeSH
- implantované elektrody MeSH
- krysa rodu rattus MeSH
- midazolam farmakologie MeSH
- modely nemocí na zvířatech MeSH
- muscimol farmakologie MeSH
- neurosteroidy farmakologie MeSH
- potkani Wistar MeSH
- receptory GABA-A účinky léků metabolismus MeSH
- záchvaty farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
Předvakcinační a povakcinační vyšetření protilátek proti kmenům obsažených ve vakcínách pro sezónu 2022/2023 bylo zajištěno u 104 pacientů dialyzačních středisek. Hodnocení registrovaných vakcín potvrdilo jejich význam při prevenci chřipky u dialyzovaných.
Pre-vaccination and post-vaccination screening of antibodies against the strains included in the 2022/2023 vaccines was conducted in 104 dialysis patients. The evaluation of the authorized vaccines confirmed their significant role in the prevention of influenza.
- Publikační typ
- abstrakt z konference MeSH