Adenoviral gene transfer of aspartoacylase into the tremor rat, a genetic model of epilepsy, as a trial of gene therapy for inherited epileptic disorder.
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.
Seki
Takahiro
T
Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, 1-2-3 Kasumi, 734-8551, Hiroshima, Japan. tseki@hiroshima-u.ac.jp
Matsubayashi
Hiroaki
H
Amano
Taku
T
Kitada
Kazuhiro
K
Serikawa
Tadao
T
Sakai
Norio
N
Sasa
Masashi
M
D000256:Adenoviridae / Q000235:genetics; D000581:Amidohydrolases / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D004832:Epilepsy, Absence / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D008297:Male; D051381:Rats; D013997:Time Factors; D014202:Tremor / Q000235:genetics* / Q000628:therapy*
D000581:Amidohydrolases; C019751:aspartoacylase