The role of muscarinic acetylcholine receptor-mediated activation of extracellular signal-regulated kinase 1/2 in pilocarpine-induced seizures
Version of Record online: 25 JUN 2002
Journal of Neurochemistry
Volume 82, Issue 1, pages 192–201, July 2002
How to Cite
Berkeley, J. L., Decker, M. J. and Levey, A. I. (2002), The role of muscarinic acetylcholine receptor-mediated activation of extracellular signal-regulated kinase 1/2 in pilocarpine-induced seizures. Journal of Neurochemistry, 82: 192–201. doi: 10.1046/j.1471-4159.2002.00977.x
- Issue online: 25 JUN 2002
- Version of Record online: 25 JUN 2002
- Received February 18, 2002; revised manuscript received April 15, 2002; accepted April 16, 2002.
Pilocarpine-induced seizures are mediated by the M1 subtype of muscarinic acetylcholine receptor (mAChR), but little is known about the signaling mechanisms linking the receptor to seizures. The extracellular signal-regulated kinase (ERK) signaling cascade is activated by M1 mAChR and is elevated during status epilepticus. Yet, the role of ERK activation prior to seizure has not been evaluated. Here, we examine the role of pilocarpine-induced ERK activation in the induction of seizures in mice by pharmacological and behavioral approaches. We show that pilocarpine induces ERK activation prior to the induction of seizures by both western blot and immunocytochemistry with an antibody to phosphorylated ERK. In addition, we show that the ERK pathway inhibitor SL327 effectively blocks the pilocarpine-induced ERK activation. However, SL327 pretreatment has no effect on the initiation of seizures. In fact, animals treated with SL327 had higher seizure-related mortality than vehicle-treated animals, suggesting activated ERK may serve a protective role during seizures. In addition, ERK inhibition had no effect on the development of the long-term sequelae of status epilepticus (SE), including mossy fiber sprouting, neuronal death and spontaneous recurrent seizures.