Scripps Florida scientists pinpoint how genetic mutation causes early brain damage

June 23, 2014

Scientists from the Florida campus of The Scripps Research Institute (TSRI) have shed light on how a specific kind of genetic mutation can cause damage during early brain development that results in lifelong learning and behavioral disabilities. The study, which focuses on the role of a gene known as Syngap1, was published online ahead of print by the journal Neuron. In humans, mutations in Syngap1 are known to cause devastating forms of intellectual disability and epilepsy.

“We found a sensitive cell type that is both necessary and sufficient to account for the bulk of the behavioral problems resulting from this mutation,” says Gavin Rumbaugh, PhD, who led the study. “Because we found the root biological cause of this genetic brain disorder, we can now shift our research toward developing tailor-made therapies for people affected by Syngap1 mutations.”

In the study, Rumbaugh and his colleagues used a mouse model to show that mutations in Syngap1 damage the development of glutamatergic neurons in the young forebrain, leading to intellectual disability. Higher cognitive processes, such as language, reasoning, and memory, arise in children as the forebrain develops. Repairing damaging Syngap1 mutations in these specific neurons during development prevented cognitive abnormalities, while repairing the gene in other kinds of neurons and in other locations had no effect.

“Our research suggests that if Syngap1 function can be fixed very early in development, this should protect the brain from damage and permanently improve cognitive function,” says Emin Ozkan, PhD, a first author of the study. “In theory, patients then wouldn't have to be subjected to a lifetime of therapies and worry that the drugs might stop working or have side effects from chronic use.” Read the article.

Read more