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.