ITEM METADATA RECORD
Title: Nicotine-induced dystonic arousal complex in a mouse line harboring a human autosomal-dominant nocturnal frontal lobe epilepsy mutation
Authors: Teper, Yaroslav ×
Whyte, Douglas
Cahir, Elizabeth
Lester, Henry A
Grady, Sharon R
Marks, Michael J
Cohen, Bruce N
Fonck, Carlos
McClure-Begley, Tristan
McIntosh, J. Michael
Labarca, Cesar
Lawrence, Andrew
Chen, Feng
Gantois, Ilse
Davies, Philip J
Petrou, Steven
Murphy, Mark
Waddington, John
Horne, Malcolm K
Berkovic, Samuel F
Drago, John #
Issue Date: Sep-2007
Publisher: Soc neuroscience
Series Title: Journal of neuroscience vol:27 issue:38 pages:10128-10142
Abstract: We generated a mouse line harboring an autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE) mutation: the alpha 4 nicotinic receptor S248F knock-in strain. In this mouse, modest nicotine doses (1-2 mg/kg) elicit a novel behavior termed the dystonic arousal complex (DAC). The DAC includes stereotypical head movements, body jerking, and forelimb dystonia; these behaviors resemble some core features of ADNFLE. A marked Straub tail is an additional component of the DAC. Similar to attacks in ADNFLE, the DAC can be partially suppressed by the sodium channel blocker carbamazepine or by pre-exposure to a very low dose of nicotine (0.1 mg/kg). The DAC is centrally mediated, genetically highly penetrant, and, surprisingly, not associated with overt ictal electrical activity as assessed by (1) epidural or frontal lobe depth-electrode electroencephalography or (2) hippocampal c-fos-regulated gene expression. Heterozygous knock-in mice are partially protected from nicotine-induced seizures. The noncompetitive antagonist mecamylamine does not suppress the DAC, although it suppresses high-dose nicotine-induced wild-type-like seizures. Experiments on agonist-induced Rb-86(+) and neurotransmitter efflux from synaptosomes and on alpha 4S248F beta 2 receptors expressed in oocytes confirm that the S248F mutation confers resistance to mecamylamine blockade. Genetic background, gender, and mutant gene expression levels modulate expression of the DAC phenotype in mice. The S248F mouse thus appears to provide a model for the paroxysmal dystonic element of ADNFLE semiology. Our model complements what is seen in other ADNFLE animal models. Together, these mice cover the spectrum of behavioral and electrographic events seen in the human condition.
URI: 
ISSN: 0270-6474
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory for Biological Psychology
Radiology
Theragnostic Laboratory (+)
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy

 




All items in Lirias are protected by copyright, with all rights reserved.

© Web of science