Role of Exercise in Increasing Newly-Born Granule Cells and Reducing Seizure Susceptibility

Epilepsy is a lifelong disorder characterized by hyperexcitability of neurons resulting in seizures. Although no cure is known, exercise can ameliorate symptoms by reducing seizure susceptibility. The exact mechanisms of which are unclear. Interestingly, hippocampal dentate gyrus (DG) granule cells (GCs), the principal excitatory cell type in the DG, increase in proportion to the amount of exercise performed, suggesting a role in reducing seizure susceptibility. Our hypothesis is that the exercise-induced generation of newly-born DGGCs underlies the reduced seizure susceptibility. To test this, comparisons of the effects of exercise on seizure severity in wild-type and DNMT mice, which do not produce newly-born DGGCs, will be made. Both wild-type and DNMT mice will be divided into 2 groups, one of which will be given running wheels. After two weeks, all groups will be injected intraperitoneally with kainate to trigger status epilepticus. Seizure severity will then be quantified for 4 hours using the Racine scale. The animals will then be sacrificed and newly-born DGGC numbers will be determined using a BrdU stain. Next, correlations between amount of exercise, increased DGGC count, and racine scores will be made. For wild-type mice, exercise is expected to have a positive correlation with DGGC count but an inverse correlation with number of seizures. DNMT mice are not expected to benefit from exercise due to their lack of newly-born DGGCs. This experiment will help determine the role, if any, that immature DGGCs have on epileptic attacks.