The effect of exercise on kainic acid induced seizures
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Studies have demonstrated that exercise decreases the symptoms of a variety of neurological disorders. Research in our laboratory has revealed that exercise up-regulates prepro-galanin messenger RNA levels in the locus coeruleus after 3 weeks of physical activity in rats. Several other studies have demonstrated that galanin decreases neuronal hyperexcitability both in vivo and in vitro. These findings support the hypothesis that exercise may diminish neural hyperexcitability, possibly through a galaninergic mechanism. The first two experiments (Chapter 3) tested whether voluntary activity wheel running would protect against kainic acid-evoked seizures and whether galaninergic signaling is a necessary factor. The third experiment (chapter 4) used in-vivo voltammetry during kainic acid-induced seizures to compare glutamate release in the hippocampus of rats allowed free access to an activity wheel or sedentary housing. In the first experiment, rats remained sedentary or were given access to running wheels for 3 weeks. After this period, rats received an intraperitoneal (IP) injection of 0, 7 10 or 14 mg/kg kainic acid. Activity wheel running decreased the severity of or eliminated the seizure behaviors and hippocampal c-fos activation induced by kainic acid. In the second experiment rats were injected intracerebroventriculary (ICV) with .2 or .4 µg of kainic acid following either an injection of M-40 (a galanin antagonist) or saline. Activity wheel running decreased the severity of the behavioral reactions to kainic acid at the .2 µg dose, and M-40 injection decreased this effect. In contrast, there were no detectable differences in behavior or cell loss at the .4 µg dose between exercising and sedentary rats. In the third experiment extracellular hippocampal glutamate was significantly reduced for 30 minutes post injection in exercising compared to sedentary subjects. These findings indicate that exercise induced up-regulation of galanin is a necessary factor in exercise-induced reduction in seizures. Exercise may also reduce excitability by modulating glutamate release.