Author Seki T, Matsubayashi H, Amano T, Kitada K, Serikawa T, Sakai N, Sasa M.
Title Adenoviral gene transfer of aspartoacylase into the tremor rat, a genetic model of epilepsy, as a trial of gene therapy for inherited epileptic disorder.
Journal Neurosci. Lett.
Abstract The tremor rat (tm/tm) is a genetic model of epilepsy that exhibits absence-like seizures characterized by 5-7 Hz spike-wave-like complexes in cortical and hippocampal electroencephalograms (EEGs). A deletion of the aspartoacylase (ASPA) gene and resultant high levels of N-acetyl-aspartate (NAA) in the brain have been found in tremor rats. We attempted to determine whether gene transfer of ASPA inhibited absence-like seizures in tremor rats using recombinant adenovirus. Recombinant adenovirus (5x10(7) pfu) carrying the rat ASPA gene (AxASPA) or beta-galactosidase gene (AxLacZ), as a control virus, was intracerebroventricularly administered to premature tremor rats aged 7 weeks. Cortical and hippocampal EEG were recorded with chronically implanted electrodes before and after viral administration. The absence-like seizures were increased in AxLacZ-administered control rats with age. However, the increase was significantly inhibited in AxASPA-administered rats at 1 week after treatment. These results suggest that gene transfer of ASPA is effective in inhibiting the generation of absence-like seizures, probably by reducing the NAA level.
Volume 328(3)
Pages 249-52
Published 2002-8-16
PII S0304394002005220
PMID 12147318
MeSH Adenoviridae / genetics Amidohydrolases / genetics* Animals Disease Models, Animal Epilepsy, Absence / genetics Female Gene Transfer Techniques Genetic Therapy* Male Rats Time Factors Tremor / genetics* Tremor / therapy*
IF 2.173
Times Cited 14
Rats SER/Kyo(strainID=28)