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A control system analysis of the dynamic response of N-methyl-D-aspartate glutamate receptors to alcoholism and alcohol withdrawal

Overview of attention for article published in Theoretical Biology and Medical Modelling, May 2015
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Title
A control system analysis of the dynamic response of N-methyl-D-aspartate glutamate receptors to alcoholism and alcohol withdrawal
Published in
Theoretical Biology and Medical Modelling, May 2015
DOI 10.1186/s12976-015-0004-3
Pubmed ID
Authors

Carlos A Gutierrez, Mary M Staehle

Abstract

N-methyl-D-Aspartate (NMDA) and its receptors (NMDAR) play a critical role in glutamatergic neurotransmission. Ethanol molecules inhibit these receptors, and if the brain is exposed to ethanol chronically, NMDA-induced glutamatergic changes can result in physical dependence to ethanol in order to sustain normal brain function. In these cases, removal of ethanol from the system results in excitotoxic withdrawal. One compensatory mechanism the brain uses to regulate extracellular glutamate concentration is modulating the number of NMDARs at the synapse. Previous work has shown that the number of functional NMDARs at the synapse can be changed by three mechanisms: additional receptors can be synthesized and inserted, receptors can be recruited to the synapse from extrasynaptic regions, or the functionality of existing receptors can be modified. In this study, we consider the dynamic relocation control of NMDARs in response to chronic alcoholism and withdrawal. Specifically, we (1) propose and construct a mathematical model of the relocation control as a negative feedback system with an explicit set point, (2) investigate the effect of various ethanol consumption and withdrawal profiles on the NMDAR population, and (3) propose and calculate quantitative measures for the extent of withdrawal based on modeled NMDAR populations. A relocation-only model with an explicit set point was developed. The model was shown to apply across a wide range of controller parameters. The results suggest that withdrawal severity does not depend upon the dynamics involved in the development of dependence, and that regulating the blood alcohol level throughout the progression of withdrawal can minimize excitotoxic withdrawal symptoms. The negative feedback control system produced characteristic behaviors of NMDAR populations in response to simulations of alcohol dependence and abrupt withdrawal. The model can also predict the severity of excitotoxic withdrawal following various alcohol consumption and/or withdrawal patterns in order to generate testable hypotheses regarding ameliorating withdrawal.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 10 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 10 100%

Demographic breakdown

Readers by professional status Count As %
Student > Doctoral Student 2 20%
Researcher 2 20%
Student > Ph. D. Student 1 10%
Student > Bachelor 1 10%
Professor > Associate Professor 1 10%
Other 1 10%
Unknown 2 20%
Readers by discipline Count As %
Medicine and Dentistry 3 30%
Neuroscience 2 20%
Biochemistry, Genetics and Molecular Biology 1 10%
Agricultural and Biological Sciences 1 10%
Unknown 3 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 20 May 2015.
All research outputs
#15,333,503
of 22,805,349 outputs
Outputs from Theoretical Biology and Medical Modelling
#171
of 287 outputs
Outputs of similar age
#156,680
of 265,295 outputs
Outputs of similar age from Theoretical Biology and Medical Modelling
#7
of 7 outputs
Altmetric has tracked 22,805,349 research outputs across all sources so far. This one is in the 22nd percentile – i.e., 22% of other outputs scored the same or lower than it.
So far Altmetric has tracked 287 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 7.4. This one is in the 27th percentile – i.e., 27% of its peers scored the same or lower than it.
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 265,295 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 32nd percentile – i.e., 32% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 7 others from the same source and published within six weeks on either side of this one.