A tiny RNA appears to play a role in producing major depression, the mental disorder that affects as many as 250 million people a year worldwide.
Major depression, formally known as major depressive disorder, or MDD, brings increased risk of suicide and is reported to cause the second-most years of disability after low-back pain.
University of Alabama at Birmingham researchers have found that amounts of this microRNA are significantly elevated in the brains of experimental rats with induced depression from corticosterone treatment, in the post-death brains of humans diagnosed with MDD and in peripheral blood serum from living patients with MDD, according to a study by led by Yogesh Dwivedi, Ph.D., the Elesabeth Ridgely Shook Endowed Professor and director of Translational Research, UAB Mood Disorders Program, Department of Psychiatry.
This microRNA -- miR-124-3p -- is thus a potential therapeutic target for novel drug development, and it can serve as a putative biomarker for MDD pathogenesis.
Micro RNAs, or miRNAs, interact with messenger RNA after the miRNA is exported from the cell nucleus and processed by a team of enzymes. MiRNAs are robust players of gene regulation in cells, and there are more than 1,300 different miRNAs at work in the brain.
In previous work, Dwivedi and colleagues had seen that a set of miRNAs were coordinately regulated in the prefrontal cortex of the brains of MDD subjects. The prefrontal cortex, known for controlling the executive function of the brain, is critically involved in the response to stress, by regulating the endocrine glands known as the hypothalamic-pituitary-adrenal axis. The adrenal gland produces the stress hormone cortisol in humans and corticosterone in rodents.
To see if stress plays a role in the coordinated regulation of prefrontal cortex miRNAs, the UAB researchers then turned to a rat depression model. They found that rats treated with corticosterone to induce depression-like behavior showed coordinated dysregulation of miRNAs in the prefrontal cortex, and the most significantly affected miRNA was miR-124-3p.
Their current paper, previewed in the journal Neuropsychopharmacology, examined the relevance of miR-124-3p in MDD pathogenesis.
Using computer analysis of genome sequences, the researchers:
In neuroblastoma cells grown in culture:
In prefrontal cortex neurons from depression-model rats treated with corticosterone:
"Altogether," the UAB researchers conclude, "this is the first comprehensive and mechanistic study at in-vitro and in-vivo levels which demonstrates that, not only are there consistent depression-associated changes in the expression of miR-124-3p across different species, but also the genes that are targets of this miRNA are highly dysregulated, showing altered response at functional level."
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