NEW YORK, NY — A single genetic abnormality can cause significant problems in the brain. This colorful cross-section of a mouse brain highlights a possible way to reverse that.

In this new study, a snippet of mouse DNA was removed to partially mimic a human condition caused by an absent chunk of chromosome 22. People with this condition, called 22q11.2 deletion syndrome, have a high risk of schizophrenia and suffer from memory impairments, social difficulties and mood-related symptoms. 

These people’s neurons, when grown in the lab, produced unusually high levels of the protein EMC10, Zuckerman Institute researchers found. This caused the neurons to form misshapen branches and activate poorly. Treating mice with small DNA fragments known as antisense oligonucleotides (yellow-green) reduced EMC10 protein levels and undid this damage. This improved mice’s ability to navigate mazes and recognize other mice

“Moderate reductions in EMC10 are both effective and safe in animal models, offering hope for potential mechanism-targeted therapies in humans,” said Zuckerman Institute Principal Investigator Joseph Gogos, MD, PhD, the study’s corresponding author. Dr. Gogos is also codirector of Columbia's Stavros Niarchos Foundation Center for Precision Psychiatry and Mental Health as well as a professor of Physiology, Neuroscience and Psychiatry at Columbia’s Vagelos College of Physicians and Surgeons.

Read more in the eLife study published today, with first authors Pratibha Thakur and Martin Lackinger from the Gogos lab.