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:
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.
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:
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.
For humans:
In 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 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.”
the fact that once a year we just put the clocks forward an hour and say that’s how it’s gonna be for 6 months, and then put it back an hour and say that’s how it’s gonna be now is actual proof that time does not exist and is purely a social construct that means literally nothing
it breaks my heart when i see survivors of emotional abuse who were so harshly invalidated, punished and tortured for their own emotions they now don’t dare to feel, they have to ask someone else for every single feeling if it’s okay, if it’s overreacting, if it’s logical, if it’s acceptable for them to feel it, if they have a good enough reason to feel the way they do, it’s fucking devastating, to suffer abuse that makes them doubt their every emotion and makes it unsafe for them to feel it, they can’t even think about expressing it because even just feeling it makes them guilty! they’re scared of their own emotions and consider every emotion that isn’t super convenient to everyone around them to be a burden and a proof of their failure to control themselves and be a proper person
feelings aren’t illogical, they aren’t wrong, they aren’t here for no reason, they aren’t a failure of self control, they aren’t a burden, they are not an inconvenience! emotions are generated from actual things that happened, they are normal reactions to things that actually happened! if you feel scared, anxious, hurt, overwhelmed, terrified, panicked, even if it seems illogical there’s a very good reason you feel this way. you aren’t supposed to control how you feel, you aren’t supposed to doubt your emotions, they are always just a reaction, they do not come from you! they’re not your failure, feeling all this is normal and logical under unbearable circumstances of abuse and torture, feeling all these as a symptom after being exposed to trauma and abuse is normal and humane.
the only reason anyone ever told you that the way you feel is wrong is because they wanted to dismiss and deny what’s happening to you. they didn’t want you to see the truth. they didn’t want to show basic human decency to you and acknowledge that something horrible happened to you and caused this shitstorm of emotions you’re going through. it’s a part of global agenda to deny abuse and oppression is happening and forcing people to act “socially acceptable” while they’re going through torture. your feelings were right all along. your feelings don’t have to be socially acceptable. nothing about you has to be socially acceptable. you’re not impossible to handle, or too much to deal with, or a burden to others, you already spent so much energy protecting everyone from what is going on inside of you, it’s been enough of doubt, enough of guilt, it’s not you who is fucked up, it’s the world who denies validation to your reality.
"Autumn.
The season of flannel shirts
With the buttons undone
And the smell of pumpkin spice wafting through homes.
The season of oversized sweaters
And leggings skin tight
With an apple pie baking in the oven
And a book held tightly between lax fingertips.
The season of crisp mornings
With leaves crunching beneath heavy boots
A scarf pinned around a bare neck
Hands shoved into large pockets.
The season of chilly evenings
And nights spent by the fireplace
With a blanket thrown over a body searching for comfort
And a soft dog cuddled in cold arms.
A season of death, or perhaps, a new beginning
When days grow shorter
And nights grow lonelier
When leaves stray too far from their branches.
A season of depression
And a tired mind
Searching for the motivation to wait for the light and the warmth
To return."
Hi guys, I hope you arent here because you feel this way, but I am assuming you are. If you don’t feel you can talk to me or are in some type of danger I am sure these resources can help.
Nothing will last forever and this is true. Please rethink any decision you are thinking about making right now. Just stop and think and see what matters and what doesnt. I really hope you have a goodnight♥ be strong and love yourself.
Have you ever thought about just walking out into traffic and letting a car hit you but then you think “well that would make the driver upset” or “man that’d be an ugly mess for someone to clean” or “my sister would be sad” so you don’t because it’d just be a big inconvenience for everyone
