Deleted DNA segment linked to ventricular enlargement in schizophrenia
Patients may suffer from what is known as “auditory hallucinations” in schizophrenia – they hear often distressing and distracting “voices” due to enlarged cerebral ventricles, which afflicts nearly 80% of schizophrenic individuals.
Uncovering the biological origins of auditory hallucinations is the first step to reducing the overall disease burden of schizophrenia – developmental neurobiologists at St. Jude Children’s Research Hospital (St. Jude) in Tennessee, US, have recently implicated two microRNAs in the biological processes that result in ventricular enlargement, as observed in a mouse models of schizophrenia. Apparently, deletion of a region on chromosome 22 (22q11.2-deletion syndrome) increases the risk of developing schizophrenia as much as 30-fold in humans, with individuals exhibiting ventricular enlargement as well.
Dr. Stanislav Zakharenkoof the St. Jude Department of Developmental Neurobiology, explains, “Schizophrenia itself is polygenic; there is no single gene that can explain all of the symptoms of this complex disease. But the 22q11-deletion syndrome model gives us an opportunity to identify the gene that contributes to ventricular enlargement.”
It was noticed that deletion of gene Dgcr8 – found within the region of DNA that is missing in 22q11-deletion syndrome – reduces two select microRNAs and subsequently increases a specific receptor on the surface of motile cilia lining the ventricle walls.When this mechanism is active, it triggers subtle changes in the ventricles: the motile cilia move more slowly, and the brain ventricles are enlarged.
“In our model, we were able to remove the microRNAs and get this effect,” Zakharenko said, and – most importantly – “we were also able to reintroduce these microRNAs and see that the ventricles and cilia return to normal.”
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