Evidence map›Paper›PMID 37566090›Full record

ArticleCells2023

Unveiling the Role of Cholesterol in Subnanomolar Ouabain Rescue of Cortical Neurons from Calcium Overload Caused by Excitotoxic Insults.

Dmitry A Sibarov, Zoia D Zhuravleva, Margarita A Ilina, Sergei I Boikov, Yulia D Stepanenko, Tatiana V Karelina, Sergei M Antonov

Open access · goldAbstract read
In one paragraph

Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.3field-weighted citation impact, top 21% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 9 citations in OpenAlex.

  1. Article
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  4. Review
  5. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 1 institution in 1 country.

Dmitry A SibarovSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Torez pr. 44, 194223 Saint-Petersburg, Russia.ORCID 0000-0002-2224-2145
Zoia D ZhuravlevaSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Torez pr. 44, 194223 Saint-Petersburg, Russia.
Margarita A IlinaSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Torez pr. 44, 194223 Saint-Petersburg, Russia.
Sergei I BoikovSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Torez pr. 44, 194223 Saint-Petersburg, Russia.ORCID 0000-0001-6231-6914
Yulia D StepanenkoSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Torez pr. 44, 194223 Saint-Petersburg, Russia.
Tatiana V KarelinaSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Torez pr. 44, 194223 Saint-Petersburg, Russia.
Sergei M AntonovSechenov Institute of Evolutionary Physiology and Biochemistry of the Russian Academy of Sciences, Torez pr. 44, 194223 Saint-Petersburg, Russia.ORCID 0000-0002-0644-9330
Institute of Evolutionary Physiology and Biochemistry · RU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Na/K-ATPase maintains transmembrane ionic gradients and acts as a signal transducer when bound to endogenous cardiotonic steroids. At subnanomolar concentrations, ouabain induces neuroprotection against calcium overload and apoptosis of neurons during excitotoxic stress. Here, the role of lipid rafts in interactions between Na/K-ATPase, sodium-calcium exchanger (NCX), and N-methy-D-aspartate receptors (NMDARs) was investigated. We analyzed 0.5-1-nanometer ouabain's effects on calcium responses and miniature post-synaptic current (mEPSCs) frequencies of cortical neurons during the action of NMDA in rat primary culture and brain slices. In both objects, ouabain attenuated NMDA-evoked calcium responses and prevented an increase in mEPSC frequency, while the cholesterol extraction by methyl-β-cyclodextrin prevented the effects. The data support the conclusions that (i) ouabain-induced inhibition of NMDA-elicited calcium response involves both pre- and post-synapse, (ii) the presence of astrocytes in the tripartite synapse is not critical for the ouabain effects, which are found to be similar in cell cultures and brain slices, and (iii) ouabain action requires the integrity of cholesterol-rich membrane microdomains in which the colocalization and functional interaction of NMDAR-transferred calcium influx, calcium extrusion by NCX, and Na/K-ATPase modulation of the exchanger occur. This regulation of the molecules by cardiotonic steroids may influence synaptic transmission, prevent excitotoxic neuronal death, and interfere with the pharmacological actions of neurological medicines.

Indexed as

CalciumOuabainAdenosine TriphosphatasesAnimalsCholesterolNeuronsN-MethylaspartateRatsAdenosine TriphosphatasesCalciumCholesterolN-MethylaspartateOuabaincalciumcholesterolNa/Ca exchangerNa/K-ATPaseneuronsNMDA receptor

Identifiers

PMID37566090
PMCPMC10417153
OpenAlexW4385611105

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.