| Title : The alpha4 Nicotinic Acetylcholine Receptor Is Necessary for the Initiation of Organophosphate-Induced Neuronal Hyperexcitability - Andrew_2024_Toxics_12_ |
| Author(s) : Andrew PM , Feng W , Calsbeek JJ , Antrobus SP , Cherednychenko GA , MacMahon JA , Bernardino PN , Liu X , Harvey DJ , Lein PJ , Pessah IN |
| Ref : Toxics , 12 : , 2024 |
| Abstract : Acute intoxication with organophosphorus (OP) cholinesterase inhibitors can produce seizures that rapidly progress to life-threatening status epilepticus. Significant research effort has been focused on investigating the involvement of muscarinic acetylcholine receptors (mAChRs) in OP-induced seizure activity. In contrast, there has been far less attention on nicotinic AChRs (nAChRs) in this context. Here, we address this data gap using a combination of in vitro and in vivo models. Pharmacological antagonism and genetic deletion of alpha4, but not alpha7, nAChR subunits prevented or significantly attenuated OP-induced electrical spike activity in acute hippocampal slices and seizure activity in mice, indicating that alpha4 nAChR activation is necessary for neuronal hyperexcitability triggered by acute OP exposures. These findings not only suggest that therapeutic strategies for inhibiting the alpha4 nAChR subunit warrant further investigation as prophylactic and immediate treatments for acute OP-induced seizures, but also provide mechanistic insight into the role of the nicotinic cholinergic system in seizure generation. |
| ESTHER : Andrew_2024_Toxics_12_ |
| PubMedSearch : Andrew_2024_Toxics_12_ |
| PubMedID: 38668486 |
Andrew PM, Feng W, Calsbeek JJ, Antrobus SP, Cherednychenko GA, MacMahon JA, Bernardino PN, Liu X, Harvey DJ, Lein PJ, Pessah IN (2024)
The alpha4 Nicotinic Acetylcholine Receptor Is Necessary for the Initiation of Organophosphate-Induced Neuronal Hyperexcitability
Toxics
12 :
Andrew PM, Feng W, Calsbeek JJ, Antrobus SP, Cherednychenko GA, MacMahon JA, Bernardino PN, Liu X, Harvey DJ, Lein PJ, Pessah IN (2024)
Toxics
12 :