Endosomal NHE6 in Long-Range Connectivity and Autism

Human mutations in NHE6 represent a novel autism-related developmental brain disorder. Such syndromic forms of autism have provided critical traction for discerning disease mechanisms and identifying potential treatment targets. Dr. Morrow’s group investigated an interesting and novel cellular mechanism, namely modulation of endosomal signaling through regulation of intra-endosomal proton concentration. The hope was that they would link this mechanism to points of convergence for gene mechanism in autism, namely development of long-range circuitry, axonal branching and relevant signaling pathways. In addition, they tested a link between NHE6 and fever. Many parental reports have strongly suggested improvements in autism symptoms with fever, and neuronal pH has been pinpointed as one mediator of the effects of systemic fever on neuronal excitability. Dr. Morrow’s group sought to reverse the cellular defects observed via addition of exogenous signaling molecules. Finally, they attempted to develop a model for autistic regression in response to stress. The research on this project was primarily led in Dr. Morrow’s lab. Dr. Morrow worked in the setting of the Institute for Brain Science at Brown University. He  collaborated with Dr. Julie Kauer, an electrophysiologist with over 20 years of experience in synaptic physiology and plasticity, and Dr. Pietro DeCamilli, a renowned neuronal cell biologist in the area of endocytosis. The hope was that this pilot project would have broad impact in the field of autism because it would identify novel cellular mechanisms that are tightly linked to potential therapeutic strategies.