Evidence map›Paper›PMID 25982851›Full record

ArticleTheoretical biology & medical modelling2015

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

Carlos A Gutierrez, Mary M Staehle

Open access · hybridAbstract read
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Article in Theoretical biology & medical modelling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
0.1field-weighted citation impact, top 52% of its field
1 · What the graph read from it

What it found

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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

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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

2 citing papers in PubMed, 2 citations in OpenAlex.

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4 · The record

Corrections and comments

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5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Carlos A GutierrezDepartment of Chemical Engineering, Rowan University, 201 Mullica Hill Road, 08028, Glassboro, NJ, USA. gutierrec0@students.rowan.edu.
Mary M StaehleDepartment of Chemical Engineering, Rowan University, 201 Mullica Hill Road, 08028, Glassboro, NJ, USA. staehle@rowan.edu.
Rowan University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundN-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.

methodsIn 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.

resultsA 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.

conclusionsThe 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.

Indexed as

Feedback, PhysiologicalAlcohol DrinkingAlcoholismComputer SimulationHumansModels, BiologicalReceptors, N-Methyl-D-AspartateSubstance Withdrawal SyndromeReceptors, N-Methyl-D-Aspartate

Identifiers

PMID25982851
PMCPMC4455702
OpenAlexW2149928787

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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 OpenQuestion graph.