Down syndrome is a well known cause of mental retardation and other medical problems, including early onset of Alzheimer disease. It has long been known that Down syndrome is associated with an individual having an additional copy of chromosome 21. Research findings reported in the July 18 advanced online publication of Nature Neuroscience have narrowed down the critical genetic elements responsible for some aspects of Down syndrome.
A team of scientists from the Uniformed Services University of the Health Sciences (USU) and Children's National Medical Center (CNMC), led by Zygmunt Galdzicki, Ph.D., associate professor of Anatomy, Physiology and Genetics, USU, and Tarik F. Haydar, Ph.D., CNMC, now associate professor, Department of Anatomy and Neurobiology, Boston University School of Medicine, and corresponding author on the study), were able to identify Olig1 and Olig2 as two genes specific to the critical region of chromosome 21 associated with Down syndrome by using a specifically-engineered modification of the golden standard Down syndrome mouse model, Ts65Dn.
Previous studies including those by co-author Tyler Best, Ph.D., while a graduate student at USU, suggested that inhibitory activity is stronger in the Ts65Dn brain. This led researchers at USU and Children's to hypothesize that genes controlling the inhibitory tone of the brain contribute to the cognitive changes associated with Down syndrome. By manipulating Olig1 and Olig2, genes present on the extra chromosome 21, the researchers were able to normalize key aspects of the inhibitory tone in brain regions involved in learning and memory. Thus, the balance of excitatory to inhibitory neurons is critically regulated by extra copies of these genes and they can drastically modify neurological development in Down syndrome.