Research

Research in the Naegele Laboratory aims to understand at a mechanistic level, how neurodegenerative changes, axonal sprouting, and aberrant neurogenesis contribute to epileptogenesis and spontaneous seizures in temporal lobe epilepsy.

Stem Cell Therapy for treating temporal lobe epilepsy. We are studying the survival, migration, and integration of transplanted murine and human ES cell-derived neural stem cells in the dentate gyrus of mice following kainic acid or pilocarpine-induced seizures (in collaboration with Laura Grabel and Gloster Aaron’s labs). We also study fetal neural stem cells harvested from the ganglionic eminence, a region of the forebrain giving rise to GABAergic interneurons and oligodendrocytes. For this work, we are utilizing several lines of transgenic mice that express fluorescent reporter constructs to allow us to track transplanted cells and determine cell fates. We assess the disease-modifying effects of GABAergic progenitor grafts by long-term video-EEG recordings of mice with recurrent spontaneous seizures and are measuring seizure suppression. Our research combines molecular and cellular approaches to understand how transplanted cells integrate and modify host brain circuits. Some of the experimental approaches in the laboratory include hippocampal and cortical cultures, in utero electroporation, fluorescent in situ hybridization, BrdU birthdating, stains for apoptosis and neurodegeneration (TUNEL, active caspase-3, FluoroJade-B), immunohistochemistry, confocal microscopy, and gene knock-ins and knock-downs.

Striatal Enriched Phosphatase (STEP) and Seizure thresholds (in collaboration with the labs of Paul Lombroso (Yale University) and Gloster Aaron (Wesleyan University). The mechanisms leading to recurrent seizures and epilepsy are not well understood. Recent work in the lab has identified a role for STriatal Enriched Phosphatase in reducing seizure thresholds. STEP regulates NMDA receptors and extracellular regulated kinase (ERK). Both of these proteins play critical roles in neuronal survival and excitability. Studies are exploring the mechanisms for seizure resistance in STEP knockout mice, hippocampal slices, and neuronal cell cultures derived from the hippocampus of these mice.

If you are interested in learning more about our work or in applying for a position in the laboratory, please contact Dr. Janice Naegele (Email jnaegele@wesleyan.edu; Telephone 860 685-3232).