| Title : Protective effects of N-methyl-D-aspartate receptor antagonism on VX-induced neuronal cell death in cultured rat cortical neurons - Wang_2008_Neurotox.Res_13_163 |
| Author(s) : Wang Y , Weiss MT , Yin J , Tenn CC , Nelson PD , Mikler JR |
| Ref : Neurotox Res , 13 :163 , 2008 |
| Abstract : Exposure of the central nervous system to organophosphorus (OP) nerve agents induces seizures and neuronal cell death. Here we report that the OP nerve agent, VX, induces apoptotic-like cell death in cultured rat cortical neurons. The VX effects on neurons were concentration-dependent, with an IC(50) of approximately 30 microM. Blockade of N-methyl-D-aspartate receptors (NMDAR) with 50 microM. D-2-amino-5-phosphonovalerate (APV) diminished 30 microM VX-induced total cell death, as assessed by alamarBlue assay and Hoechst staining. In contrast, neither antagonists of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) nor metabotropic glutamate receptors (mGluRs) had any effect on VX-induced neurotoxicity. VX-induced neuronal cell death could not be solely attributed to acetylcholinesterase (AChE) inhibition, since neither the reversible pharmacological cholinesterase inhibitor, physostigmine, nor the muscarinic receptor antagonist, atropine, affected VX-induced cell death. Importantly, APV was found to be therapeutically effective against VX-induced cell death up to 2 h post VX exposure. These results suggest that NMDARs, but not AMPARs or mGluRs, play important roles in VX-induced cell death in cultured rat cortical neurons. Based on their therapeutic effects, NMDAR antagonists may be beneficial in the treatment of VX-induced neurotoxicities. |
| ESTHER : Wang_2008_Neurotox.Res_13_163 |
| PubMedSearch : Wang_2008_Neurotox.Res_13_163 |
| PubMedID: 18522896 |
Wang Y, Weiss MT, Yin J, Tenn CC, Nelson PD, Mikler JR (2008)
Protective effects of N-methyl-D-aspartate receptor antagonism on VX-induced neuronal cell death in cultured rat cortical neurons
Neurotox Res
13 :163
Wang Y, Weiss MT, Yin J, Tenn CC, Nelson PD, Mikler JR (2008)
Neurotox Res
13 :163