American scientists have moved a step closer to unravelling how abnormal microRNAs, molecules that regulate expression of numerous genes, may contribute to the behavioural and neuronal deficits related to schizophrenia and other brain disorders.
Working with mouse models at Columbia University Medical Center, the researchers discovered a previously unknown alteration in the production of microRNAs that may give rise to such deficits.
AdvertisementFor their study, the researchers had modelled the animal subjects to have the same chromosome deletions that were found deleted in schizophrenia patients in previous studies.
"We've known for some time that individuals with 22q11.2 microdeletions are at high risk of developing schizophrenia," Nature Genetics quoted Dr. Maria Karayiorgou, who was instrumental in identifying deletions of 22q11.2 as a primary risk factor for schizophrenia in humans several years earlier, as saying.
"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 behavioural and cognitive deficits associated with the disease," the researcher added.
The researchers examined what effects the genetic deletion could have on the expression of over 30,000 genes in specific areas of the brain, and found that it indeed affected the gene family of microRNAs.
The team was suspicious that a gene called Dgcr8 might be fundamental to such effects, and so they produced a mouse deficient for the Dgcr8 gene.
When tested the animal on a variety of cognitive, behavioural and neuroanatomical tests, they observed the same deficits often observed in people with schizophrenia.
"Our studies show that alterations in microRNA processing result in synaptic and behavioral deficits," said Dr. Joseph A. Gogos, associate professor of physiology and neuroscience at Columbia University Medical Center.
With this work, the researchers claim to have moved a step closer to understanding the biological mechanisms responsible for schizophrenia.
"Our hope is that the more we know about the genes involved in schizophrenia, the more targeted treatment can be," said Dr. Gogos.
"Much in the way that cancer patients who have tested for a particular gene, such as BRAC1, can be tested and then treated with protocols designed specifically for them, we want to be able to know enough about the schizophrenic brain to target treatments to individual patients," he added.
The next step for the researchers is to find the many genes whose expression is controlled by the identified deficient microRNAs, which could in turn be involved in the pathogenesis of schizophrenia.
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