Exercise is considered beneficial to overall health and may enhance the resiliency of the body to insult. Here, we investigated the ability of exercise to modulate neurotoxicity caused by kainic acid in male C57Bl/6J mice. Forced walking was achieved in a motorized exercise wheel (10 s/rev., 30 min., 4:00 P.M.). Mice were trained for three days, then exercised for 14 days prior to kainate treatment. On day 14 of exercise, mice received an injection of saline or kainic acid (20 mg/kg, intraperitoneal, at 12:00 P.M.). Additional non-exercised mice received similar injections for a total of four groups: saline, kainate, wheel saline, wheel kainate. Seizure severity was scored according to the Racine scale. At 24 hours post-injection, mice were decapitated, the brain was removed and bisected; the left hippocampus was dissected for analysis of GFAP by ELISA while the right hemisphere was immersion fixed for histological analysis of neurodegeneration by Fluoro-Jade B staining. Body, thymus, and spleen weights were recorded, and plasma was prepared for analysis of corticosterone levels. The 24 hour time point for sacrifice was selected based on previous experimentation evaluating kainate-induced neurodegeneration, but preceded the peak of induction of GFAP. Kainic acid treatment caused minimal seizures (mouth and facial movements). Fluoro-Jade B staining revealed fluorescent pyramidal cells in kainate-treated animals indicating neuronal damage; no fluorescent neurons were observed in any exercised mice. GFAP levels were not significantly different between groups, but protein levels were slightly elevated in kainate treated mice, and attenuated in exercised animals. Additional time points will be examined which correlate with the peak of reactive gliosis. No differences in body or organ weights were observed; however, there was a trend of decreasing thymus weight in exercised animals. These data suggest exercise may be protective against kainate-induced excitotoxicity. The generality of these findings for other types of brain insults will be the topic of future investigations.
The Toxicologist. Society of Toxicology 44th Annual Meeting and ToxExpo, March 6-10, 2005, New Orleans, Louisiana