Research out of the George Washington University (GW), published in the journal Proceedings of the National Academy of Sciences (PNAS), indicates for the first time that genetic lesions identified with autism and other behavioral diseases disturb cellular and molecular mechanisms that confirm typical development of a key type of cortical neuron: the interneuron.
Anthony-Samuel LaMantia, Ph.D., professor of pharmacology and physiology at the GW School of Medicine and Health Sciences (SMHS) and director of the GW Institute for Neuroscience, along with post-doctoral fellow Daniel Meechan, Ph.D. and Thomas Maynard, Ph.D., associate research professor of pharmacology and physiology at GW SMHS, authored the study titled “Cxcr4 regulation of interneuron migration is disrupted in 22q11.2 deletion syndrome.”
LaMantia and his co-researchers found that interneurons are unable to appropriately shift into the cortex where they are required to manage cortical circuit action. The key cause for this as shown by the research was due to diminished expression of movement of a critical regulatory passageway for migration, the Cxcr4 cytokine receptor.
This reveals another piece of the puzzle in a genetic developmental disorder that causes behavioral diseases such as autism. For nine years, LaMantia and his colleagues have been investigating how behavioral disorders such as autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia occur all through early brain development. Said LaMantia, “These two pieces tell us that in very early development, those with 22q11.2 deletion syndrome do not make enough cells in one case, and do not put the other cells in the right place. This occurs not because of some degenerative change, but because the mechanisms that make these cells and put them in the right place during the first step of development have gone awry due to mutation.”
LaMantia’s next research step is to further explore the molecular mechanisms that disturb the increase of projection neurons and migration of interneurons. “If we understand that better and understand its consequences, we can go about fixing it,” said LaMantia. “We want to understand why cortical circuits don’t get built properly due to the genetic deletion of chromosome 22.”