New Research Illustrates the Impact of Gene MutationNeuropsychiatric disorders such as intellectual disability, autism, schizophrenia and epilepsy affect high numbers of people in intricate and highly individual ways. And their causes are equally complex and in some cases mysterious. Scientists established that genetic mutations, specifically in the CNTNAP2 gene, can cause such conditions in humans, but the reason why remained unclear. According to new research from Northwestern Medicine, the answer may lie in the synapses of cells.
When functioning properly, the CNTNAP2 gene encodes Caspr2 proteins, which in turn send molecules called AMPA glutamate receptors into the synapses, sites where communication between brain cells occurs. This process helps keep the synapses large and healthy.
The Northwestern Medicine team, led by Peter Penzes, PhD, professor of Physiology and Psychiatry and Behavioral Sciences at Northwestern University Feinberg School of Medicine, studied neurons from mice that were missing the Caspr2 protein. The scientists found that the synapses in these neurons were smaller and weaker. Furthermore, they discovered that that the key molecules were stuck inside the cells rather than having been sent to the synapses. The findings suggest that when CNTNAP2 is mutated and less of the protein is produced, human cells, much like those in the mice neurons, do not receive the benefits to keep the synapses large and strong.
The research also established that the absence of the protein had no effect on young, developing neurons. The scientists determined that the protein is only expressed and required by the cell later. Penzes and his team hypothesize that this could explain why so many of these neuropsychiatric disorders, like schizophrenia, for example, do not emerge until later in life when the cells are mature.
Notably, this type of abnormality has never been reported for a gene involved in neuropsychiatric conditions. The team hopes the study will pave the way for future research on how genes that cause these diseases can affect brain function in other ways.