Researchers illuminated a window into how abnormalities in miRNAs may contribute to the behavioral and neuronal deficits associated with schizophrenia and possibly other brain disorders.
“We’ve known for some time that individuals with 22q11.2 microdeletions are at high risk of developing schizophrenia,” says Maria Karayiorgou, M.D., professor of psychiatry at Columbia University Medical Center. “By digging further into this chromosome, we have been able to see at the gene-expression level that abnormalities in microRNAs can be linked to the behavioral and cognitive deficits associated with the disease.”
The investigators modeled mice to have the same genetic deletion as the one observed in some individuals with schizophrenia and examined what happens in the expression of over 30,000 genes in specific areas of the brain. They discovered that the gene family of miRNAs was affected.
The Dgcr8 gene is one of the 27 included in the 22q11.2 microdeletion and has a critical role in miRNA production. When the investigators produced a mouse deficient for the Dgcr8 gene and tested it on a variety of cognitive, behavioral, and neuroanatomical tests, they observed the same deficits often observed in people with schizophrenia.
Aside from Columbia University Medical Center, researchers from Cold Spring Harbor Laboratory and University of British Columbia were also involved. The paper was published in the May 11 issue of Nature Genetics.