Epilepsy, Autism, Ketogenic Diet
The major goal of our laboratory is to elucidate the molecular and cellular mechanisms underlying the clinical anti-seizure effects of the ketogenic diet (KD), an effective non-pharmacological treatment for medically refractory epilepsy. We are also attempting to validate the neuroprotective (and potentially) disease-modifying effects of the KD. Recent published studies have focused on the antioxidant properties of ketone bodies – which are produced during KD treatment – and fatty acids (particularly, polyunsaturated fatty acids). Our laboratory utilizes state-of-the-art cellular in vitro electrophysiological techniques (i.e., single-channel and whole-cell patch-clamp, and IR-DIC slice recordings), combined with molecular-genetic approaches, behavioral assessments (e.g., continuous video-EEG monitoring, high-density multi-electrode recordings of brain slices, behavioral assays), and cellular fluorescence imaging. The principal animal model of epilepsy studied in our laboratory is the epileptic Kcna1-null mouse, which develops spontaneous recurrent seizures early in post-natal development. Additionally, our laboratory has recently been investigating pathophysiological mechanisms and therapeutic strategies (notably, metabolism-based) in animal models of autism spectrum disorder (specifically, the prenatal valproic acid rat model, and the BTBR mouse model).