Adenoviral gene transfer of aspartoacylase into the tremor rat, a genetic model of epilepsy, as a trial of gene therapy for inherited epileptic disorder.

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.

• Authors: Takahiro Seki, Hiroaki Matsubayashi, Taku Amano, Kazuhiro Kitada, Tadao Serikawa, Norio Sakai, Masashi Sasa
• Journal: Neuroscience letters (Neurosci Lett) Vol. 328 Issue 3 Pg. 249-52 (Aug 16 2002) ISSN: 0304-3940 [Print] Ireland
• PMID: 12147318 (Publication Type: Journal Article)

Chemical References

• Amidohydrolases
• aspartoacylase

Topics

• Adenoviridae (genetics)
• Amidohydrolases (genetics)
• Animals
• Disease Models, Animal
• Epilepsy, Absence (genetics)
• Female
• Gene Transfer Techniques
• Genetic Therapy
• Male
• Rats
• Time Factors
• Tremor (genetics, therapy)