Biology and MB&B

Graduate Student Career Retreat 2008

Name:  S. W. Briggs, D. Austin, G. Aaron, S. L. Lin, P.J. Lombroso, Y.S. Choi,

            K. Obrietan, J.R. Naegele

   Lab:  Jan Naegele [Biology]

Abstract

Role of STEP in Hippocampal GABAergic Interneuron Death

 in Pilocarpine-Induced Status Epilepticus

Epilepsy is a common neurological disorder, affecting about 1% of the population. Mesial temporal lobe epilepsy (MTLE) is characterized by complex partial seizures that result in excitotoxic damage to the hippocampus, particularly in the hilus or polymorphic region of the dentate gyrus. In this region, GABAergic interneurons are selectively depleted by seizures, and loss of this important inhibitory neuronal population is thought to remove the "brakes" that limit runaway excitation in temporal lobe structures, leading to epileptogenesis. In the mouse pilocarpine model of MTLE, we showed that GABAergic neurons expressing high levels of STriatal Enriched Phosphatase (STEP), within the hilus and CA1 molecular layer, undergo rapid cell death following seizure-induced damage. Moreover, we demonstrated that STEP sensitizes these neurons to excitotoxicity by suppressing neuroprotective signaling through the MAP kinase pathway (Choi et al. 2007). To extend these findings, we have now examined the role of STEP in seizure generation and secondary damage. We have not found any significant difference in cell death, which may reflect either no difference in death or just be an artifact from using pilocarpine, a very severe seizure model.  However, we have found a significant resistance to pilocarpine in mice that lack STEP. The mice also demonstrate resistance to an electrical model of seizure in acute hippocampal slices.