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Effect of Cholesterol on Membrane Fluidity and Association of Aβ Oligomers and Subsequent Neuronal Damage: A Double-Edged Sword

Overview of attention for article published in Frontiers in Aging Neuroscience, August 2018
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (82nd percentile)
  • Good Attention Score compared to outputs of the same age and source (73rd percentile)

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Citations

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65 Dimensions

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113 Mendeley
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Title
Effect of Cholesterol on Membrane Fluidity and Association of Aβ Oligomers and Subsequent Neuronal Damage: A Double-Edged Sword
Published in
Frontiers in Aging Neuroscience, August 2018
DOI 10.3389/fnagi.2018.00226
Pubmed ID
Authors

Eduardo J. Fernández-Pérez, Fernando J. Sepúlveda, Christian Peters, Denisse Bascuñán, Nicolás O. Riffo-Lepe, Juliana González-Sanmiguel, Susana A. Sánchez, Robert W. Peoples, Benjamín Vicente, Luis G. Aguayo

Abstract

Background: The beta-amyloid peptide (Aβ) involved in Alzheimer's disease (AD) has been described to associate/aggregate on the cell surface disrupting the membrane through pore formation and breakage. However, molecular determinants involved for this interaction (e.g., some physicochemical properties of the cell membrane) are largely unknown. Since cholesterol is an important molecule for membrane structure and fluidity, we examined the effect of varying cholesterol content with the association and membrane perforation by Aβ in cultured hippocampal neurons. Methods: To decrease or increase the levels of cholesterol in the membrane we used methyl-β-cyclodextrin (MβCD) and MβCD/cholesterol, respectively. We analyzed if membrane fluidity was affected using generalized polarization (GP) imaging and the fluorescent dye di-4-ANEPPDHQ. Additionally membrane association and perforation was assessed using immunocytochemistry and electrophysiological techniques, respectively. Results: The results showed that cholesterol removal decreased the macroscopic association of Aβ to neuronal membranes (fluorescent-puncta/20 μm: control = 18 ± 2 vs. MβCD = 10 ± 1, p < 0.05) and induced a facilitation of the membrane perforation by Aβ with respect to control cells (half-time for maximal charge transferred: control = 7.2 vs. MβCD = 4.4). Under this condition, we found an increase in membrane fluidity (46 ± 3.3% decrease in GP value, p < 0.001). On the contrary, increasing cholesterol levels incremented membrane rigidity (38 ± 2.7% increase in GP value, p < 0.001) and enhanced the association and clustering of Aβ (fluorescent-puncta/20 μm: control = 18 ± 2 vs. MβCD = 10 ± 1, p < 0.01), but inhibited membrane disruption. Conclusion: Our results strongly support the significance of plasma membrane organization in the toxic effects of Aβ in hippocampal neurons, since fluidity can regulate distribution and insertion of the Aβ peptide in the neuronal membrane.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 113 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 113 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 27 24%
Student > Master 15 13%
Student > Bachelor 13 12%
Researcher 10 9%
Student > Doctoral Student 7 6%
Other 16 14%
Unknown 25 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 28 25%
Agricultural and Biological Sciences 11 10%
Chemistry 8 7%
Neuroscience 8 7%
Medicine and Dentistry 7 6%
Other 25 22%
Unknown 26 23%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 12. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 24 August 2018.
All research outputs
#3,048,883
of 25,375,376 outputs
Outputs from Frontiers in Aging Neuroscience
#1,176
of 5,481 outputs
Outputs of similar age
#57,432
of 337,823 outputs
Outputs of similar age from Frontiers in Aging Neuroscience
#24
of 87 outputs
Altmetric has tracked 25,375,376 research outputs across all sources so far. Compared to these this one has done well and is in the 87th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 5,481 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 14.4. This one has done well, scoring higher than 78% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 337,823 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 82% of its contemporaries.
We're also able to compare this research output to 87 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 73% of its contemporaries.