Elevation of brain GABA levels with vigabatrin (γ-vinylGABA) differentially affects GAD65 and GAD67 expression in various regions of rat brain
✍ Scribed by Sabina N. Sheikh; David L. Martin
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- English
- Weight
- 111 KB
- Volume
- 52
- Category
- Article
- ISSN
- 0360-4012
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✦ Synopsis
Previous studies have demonstrated that the expression of one of the isoforms of glutamate decarboxylase, GAD 67 , is selectively reduced in cultured cortical neurons and in rat cerebral cortex when the concentration of GABA is elevated. We asked whether the expression of GAD 67 was similarly affected by elevated GABA throughout the brain. The concentration of GABA in rat brain was increased by inhibiting GABA transaminase (GABA-T) with vigabatrin (␥-vinylGABA, GVG), an antiepileptic drug and selective inhibitor of GABA-T. Rats were injected with saline or vigabatrin (150 mg/kg) daily for 5 days, and the effects of accumulated GABA on total GAD activity and the expression of GAD 65 and GAD 67 proteins were determined in twelve brain regions. The GABA concentration was significantly elevated in all regions except amygdala and olfactory bulb after vigabatrin treatment. Total GAD activity was significantly lower than controls in six regions: cerebellum, frontal cortex, thalamus, substantia nigra, ventral tegmentum, and the remaining midbrain. The decrease in GAD activity was largest in cerebellum and thalamus (33% and 29%), while the changes in the other four areas were 15-18%. Vigabatrin treatment significantly reduced GAD 67 protein in all regions except olfactory bulb, whereas GAD 65 protein decreased significantly only in cerebellum. The failure to detect significant changes in GAD activity in regions having a significant change in GAD 67 levels is attributable to the small contribution of GAD 67 to total GAD in those regions. It is evident that there are marked regional differences in the effects of tissue GABA levels on the expression of GAD 67 .