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.
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 in Neuropsychopharmacology.
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.
In previous work, researchers 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 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.
Researchers identified eight highly potential target genes for binding by miR-124-3p, genes whose function is also reported to be critical in brain physiology during stress and MDD pathogenesis. Four of these potential target genes were significantly down-regulated in the prefrontal cortex of corticosterone-treated rats, and this down-regulation inversely correlated with miR-124-3p levels.
They showed that the four genes that were significantly down-regulated have evolutionarily conserved miR-124-3p binding sites across a wide range of higher vertebrate species.
In neuroblastoma cells grown in culture overexpression of miR-124-3p caused significant down-regulation for two of the potential target genes.
In prefrontal cortex neurons from depression-model rats treated with corticosterone resulted in significant binding by miR-124-3p to two of the potential target genes was seen, as measured from immunoprecipitated RNA-induced silencing complexes.
The locus-specific origin of for mature miR-124-3p was identified at a site on chromosome 3, out of three possible chromosomal sites, and two CpG "islands" that can act as sites from epigenetic modification by DNA methylation were identified near the miR-124 gene promoter on chromosome 3.
This miR-124-3 promoter was found to be hypo-methylated in the corticosterone-treated rats, and the gene expression of one DNA methyltransferase -- Dnmt3a -- was significantly repressed.
In human post-mortem brains of 15 controls and 15 MDD subjects, the MDD group showed significant increase in the expression of miR-124-3p, and expression of three of the potential target genes was significantly lower.
The level of miR-124-3p was significantly higher in the serum of 18 antidepressant-free MDD patients, as compared with 17 healthy controls.
"Altogether," the 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."
http://www.uab.edu/news/innovation/item/7591-dwivedi-and-major-depression
A microRNA plays role in major depression
- 2,405 views
- Added
Edited
Latest News
A drug to prevent flu-induc…
By newseditor
Posted 18 Apr
New origin of deep brain waves
By newseditor
Posted 17 Apr
Starving cells hijack prote…
By newseditor
Posted 17 Apr
Miniature battery-free epid…
By newseditor
Posted 17 Apr
Molecular causes of differe…
By newseditor
Posted 16 Apr
Other Top Stories
A wireless closed-loop system for optogenetic peripheral neuromodul…
Read more
Detecting Alzheimer's disease six months before diagnosis using AI
Read more
Inhalable form of messenger RNA created!
Read more
Safer and more efficient gene editing!
Read more
LEDs to improve health, food!
Read more
Protocols
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Modular dual-color BiAD sen…
By newseditor
Posted 31 Mar
Publications
How does the microbiota con…
By newseditor
Posted 18 Apr
The integrated stress respo…
By newseditor
Posted 18 Apr
The immunobiology of herpes…
By newseditor
Posted 17 Apr
Circulating microbiome DNA…
By newseditor
Posted 17 Apr
Spindle oscillations in com…
By newseditor
Posted 17 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar