With the aid of a four-year, $2.7 million grant from the National Institute of Mental Health, part of the National Institutes of Health (NIH), Vanderbilt University Medical Center pharmacologist Jerod Denton, PhD, and his team will pave the way for potential treatments for schizophrenia and autism spectrum disorder (ASD).
Higher ratios of excitatory-to-inhibitory synaptic transmission are seen in both ASD and schizophrenia. Correcting this imbalance could be key to treating these disorders. Denton works on potassium channels, which are found in cell membranes of virtually all organisms. Normal nerve transmission relies on the transfer of potassium ions across nerve cell membranes via these channels.
At the heart of the study is a type of inhibitory neuron called GABAergic interneurons, which connect brain regions, playing vital roles in coordinating high-frequency brain activity. As a potential source of the excitatory/inhibitory imbalance in ASD and schizophrenia, evidence now points to malfunction of a type of potassium channel, Kv3.1, special to GABAergic interneurons. Denton and his team will aim to develop Kv3.1 enhancers and test their efficacy in restoring the balance of neural activity in a mouse model of ASD. In latter stages of this work, they’ll focus on key brain areas, using various lab techniques to carefully fill in neurological details surrounding any targeted drug effects.
“This grant creates opportunities for developing critically needed tool compounds to explore the role of Kv3.1 potassium channels in autism spectrum disorder and schizophrenia,” said Denton, professor of Anesthesiology and Pharmacology. “These are some of the most challenging and costly disorders going, and we’re excited to have this opportunity to take this work forward.”
Denton’s co-investigators on the grant include Craig Lindsley, PhD, University Distinguished Professor of Pharmacology, and Brad Grueter, PhD, associate professor of Anesthesiology. The study is supported by NIH grant MH131721.