000 02235caa a22002898i 4500
001 5jlr8vqgm630-en
003 FR-PaOEC
005 20210419165835.0
006 a o d i
007 cr || |||m|n||
008 171201s2016 ||| o i|0| 0 eng d
035 _a(FR-PaOEC)
040 _aFR-PaOEC
100 1 _aSachana, Magdalini.
245 1 0 _aAdverse Outcome Pathway on binding of agonists to ionotropic glutamate receptors in adult brain leading to excitotoxicity that mediates neuronal cell death, contributing to learning and memory impairment
_h[electronic resource] /
_cMagdalini Sachana, Sharon Munn and Anna Bal-Price
260 _aParis :
_bOECD Publishing,
_c2016.
300 _a118 p. ;
_c21 x 29.7cm.
490 1 _aOECD Series on Adverse Outcome Pathways,
_x2415170X ;
_vno.6
520 3 _aUnder physiological conditions activation of glutamate ionotropic receptors such as N-methyl-D-aspartate (NMDARs), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPARs) and kainate (KARs) is responsible for basal excitatory synaptic transmission and synaptic plasticity. However, sustained over-activation of these receptors can induce excitotoxic neuronal cell death. Increased Ca2+ influx through NMDARs promotes many pathways of toxicity due to generation of free radical species, reduced ATP production, endoplasmic reticulum (ER) stress and protein aggregation. Neuronal injury induced by over-activation of these receptors and the excessive Ca2+ influx is considered an early key event of excitotoxicity. The proposed AOP is relevant to adult neurotoxicity. The MIE has been defined as a direct binding of agonists to NMDARs or indirect, through prior activation of AMPARs and/or KARs resulting in sustained NMDARs over-activation causing excitotoxic neuronal cell death, mainly in hippocampus and cortex, two brain structures fundamental for learning and memory processes.
650 4 _aEnvironment
650 4 _aSocial Issues/Migration/Health
700 1 _aMunn, Sharon.
700 1 _aBal-Price, Anna.
830 0 _aOECD Series on Adverse Outcome Pathways,
_x2415170X ;
_vno.6.
856 4 0 _aoecd-ilibrary.org
_uhttps://s443-doi-org.br.lsproxy.net/10.1787/5jlr8vqgm630-en
942 _2ddc
_cW-PAPER
999 _c358808
_d317370