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Systemic Overexpression of the α 1B ‐Adrenergic Receptor in Mice: An Animal Model of Epilepsy
Author(s) -
Kunieda Takeharu,
Zuscik Michael J.,
Boongird Atthaporn,
Perez Dianne M.,
Lüders Hans O.,
Najm Imad M.
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.2002.13202.x
Subject(s) - ictal , epilepsy , mutant , wild type , medicine , endocrinology , alpha (finance) , receptor , genetically modified mouse , transgene , biology , neuroscience , biochemistry , gene , surgery , construct validity , patient satisfaction
Summary: Purpose: A lack of selective α 1 ‐adrenergic receptor (α 1 ‐ARs) agonists and antagonists has made it difficult to clarify the precise function of these receptors in the CNS. We recently generated transgenic mice that overexpress either wild‐type or a constitutively active mutant α 1B ‐AR in tissues that normally express the receptor. Both wild‐type and mutant mice showed an age‐progressive neurodegeneration with locomotor impairment and probable stress‐induced motor events, which can be partially reversed by α 1 ‐AR antagonists. We hypothesized that the wild‐type and mutant mice may exhibit spontaneous epileptogenicity as compared with normal (nontransgenic) mice. Methods: Normal, wild‐type, and mutant mice were studied. Twenty mice (1 year old) underwent prolonged video‐EEG monitoring over a 4‐week period. Raw EEG data were blindly analyzed by visual inspection for the presence of interictal and ictal epileptic activities. Results: During the acute postoperative period (≤3 days), both wild‐type (26.1 ± 8.07 spikes/day) and mutant mice (116.87 ± 55.13) exhibited more frequent interictal spikes than did normal mice (2.17 ± 0.75; p value, <0.05), but all three groups showed EEG and clinical seizures. During the later monitoring periods (>3 days), wild‐type and mutant mice showed more frequent interictal spikes (15.44 ± 4.07; p < 0.01; and 6.05 ± 2.46; p < 0.05, respectively) as compared with normal mice (0.41 ± 0.41), but only mutant mice had spontaneous clinical seizures (means ± SEM). Conclusions: The selective overexpression of the α 1B ‐AR is associated with increased in vivo spontaneous interictal epileptogenicity and EEG/behavioral seizures. These results suggest a possible role (direct or indirect) for the α 1B ‐ARs in the development and expression of epileptogenicity.