|Protein synthesis in interneurons in Fragile X mice
by Michael Tranfaglia MD, FRAXA Medical Director, 7/1/2004
Dr. Oswald Steward is Reeve-Irvine Professor of Anatomy and Neurobiology and Director of the Reeve-Irvine Research Center at the University of California at Irvine. Dr. Steward was the first scientist to demonstrate that protein synthesis could occur in dendrites in response to synaptic activity. Prior to this discovery, dogma in neuroscience held that protein was synthesized only in the body of the cell, and then transported out to the far reaches of the dendritic arbor. We now know that protein is, indeed, synthesized in dendrites -- and FMRP is intimately involved in the process. Activity-dependent protein synthesis in dendrites is now thought to be essential for most kinds of learning and memory.
This grant will enable the Steward lab to test Fragile X knockout mice for alterations in protein synthesis in response to various kinds of activity -- seizure, fear conditioning, or different kinds of chemical stimulation. They will also look closely at alterations in regulation of protein synthesis in interneurons, an important but often overlooked population of cells in the brain which helps to coordinate activity among groups of neighboring cells. Dysfunction of interneurons may cause the seizures often seen in Fragile X, but could also account for many other observed symptoms.Messenger RNA for FMRP is especially concentrated in the dendrites of interneurons, according to previous work of the Steward group, indicating that these cells may be especially hard hit by this disorder, making further study especially important.