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NMDAR Helps You Think, So Please Reconsider That Extra Drink
Author(s) -
Sampe David,
Block Gavin,
Davis TJ,
Dong Nancy,
Freuler Jonah,
Mietkowski Mitchell,
Rowney Toni Jo,
Stoehr Noel,
Peoples Robert W.
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.lb269
Subject(s) - nmda receptor , glutamate receptor , amino acid , ethanol , chemistry , protein subunit , ion channel , neurotransmission , neuroscience , excitatory postsynaptic potential , glutamic acid , domain (mathematical analysis) , receptor , biophysics , biochemistry , psychology , biology , mathematical analysis , mathematics , gene
According to the U.S. Centers for Disease Control and Prevention, each year 88,000 people die from alcohol‐related causes in the United States. Ethanol misuse, a deadly and expensive societal problem, cost the United States $249 billion in 2010 (1). Ethanol targets many proteins in the brain. Specifically, it acts as an inhibitor of the N‐Methyl‐D‐aspartate receptor (NMDAR), which mediates much of the excitatory synaptic transmission in the brain. Normally, the NMDAR is activated when glutamic acid binds to it allowing positive ions to flow through the cell membrane; this facilitates learning and memory in the brain. However, ethanol inhibits the activity of the NMDAR, interfering with synaptic transmission. A type of glutamate ion channel receptor found in neurons, NMDAR, has four domains: the amino terminal domain, the ligand binding domain, the membrane‐associated (M) domains, and the carboxy terminal domain. NMDAR is a heterotetrameric protein with two GluN1 and two GluN2 subunits. Ethanol interacts with NMDAR in the M domains with specific amino acids including Gly638 in the GluN1 subunit as well as Phe637 and Gly826 in the GluN2B subunit (2,3). Researchers are determining the location of the strongest NMDAR‐ethanol interactions using amino acid substitutions. The Brown Deer High School SMART (Students Modeling A Research Topic) Team has designed a model of NMDAR using 3D printing technology to visualize the NMDAR‐ethanol interactions. If researchers can develop molecules to help minimize the effect of ethanol on the brain, it could reduce the cost of alcoholism to society. Support or Funding Information This work was supported by the National Institutes of of Health Science Education Partnership Award (NIH‐SEPA 1R25OD010505‐01) and the National Institutes of Health Clinical and Translational Science Award (NIH‐CTSA UL1RR031973).