TY  - GEN
AU  - Sachana,Magdalini
AU  - Munn,Sharon
AU  - Bal-Price,Anna
TI  - Adverse 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
T2  - OECD Series on Adverse Outcome Pathways,
PY  - 2016///
CY  - Paris
PB  - OECD Publishing
KW  - Environment
KW  - Social Issues/Migration/Health
N2  - Under 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
UR  - https://s443-doi-org.br.lsproxy.net/10.1787/5jlr8vqgm630-en
ER  -