Abstracts

Rationale: Alterations in the mRNA expression of GABA transporters (GATs) 1 and 3, and the osmolyte transporter sodium-myoinositol co-transporter (SMIT) have been shown to occur in epilepsy and seizure models. However, the influence of seizure activity on expression of the betaine/GABA transporter, BGT1, is unknown. BGT1 may be susceptible to regulation similar to other osmolyte-related genes, other GABA transporters, or both. Therefore, this study compared the expression of BGT1 to that of osmolyte-related genes SMIT, taurine transporter (TauT), aldose reductase (AR), and GATs 1 and 3 following status epilepticus (SE). The possible contributory role of dehydration or an inflammatory insult on gene expression was also investigated. Methods: Pilocarpine status was induced in male C57/B6 mice. Hippocampi were collected for gene expression determinations at 8 hours (h), 24 h, 72 h, one week, and four weeks post-SE. Hippocampal mRNA levels from SE animals were compared to those from hippocampi obtained from animals experiencing either an inflammatory insult (LPS, 4 mg/kg, i.p.) or 24 h water withdrawal to determine if either inflammation or dehydration could contribute to the results observed post-SE. Results: Twenty-four hours post-SE, BGT1, SMIT, and TauT mRNA expression were significantly increased. At the 72 h and 4-week time-points, BGT1, GAT1, and GAT 3 were significantly decreased. Hence, the expression of BGT1 switched from being similar to that of the osmolyte transporters at an early time-point to being more like the GABA transporters. Following SE, animals are dehydrated to a similar extent to animals that have had water withheld for 24 hours. However, the mRNA values for BGT1, TauT, and SMIT following 24-hour water withdrawal were significantly lower than the values obtained following SE. This result suggests that dehydration does not fully account for the upregulation of the osmolyte transporters following SE. Following an inflammatory insult, GAT1 and GAT3 values were not significantly different from SE animals, supporting the hypothesis that inflammation may contribute to GAT downregulation post-SE. BGT1 values, however, showed a significantly smaller decrease following LPS compared to that seen post-SE, which suggests that inflammation does not significantly contribute to the downregulation of this transporter post-SE. Conclusions: Neither plasma osmolality nor inflammation appear to fully account for the changes seen in BGT1 mRNA expression post-SE. The mediator(s) of BGT1 mRNA regulation in the brain remain(s) undetermined.