Here are 5 articles about the Impact & Inheritance of Epigenetic Changes:
Why can’t your friend “just get over” her upbringing by an angry, distant mother? Why can’t she “just snap out of it”? The reason may well be due to methyl groups that were added in childhood to genes in her brain, thereby handcuffing her mood to feelings of fear and despair.
According to the new insights of behavioral epigenetics, traumatic experiences in our past, or in our recent ancestors’ past, leave molecular scars adhering to our DNA.
Jews whose great-grandparents were chased from their Russian shtetls; Chinese whose grandparents lived through the ravages of the Cultural Revolution; young immigrants from Africa whose parents survived massacres; adults of every ethnicity who grew up with alcoholic or abusive parents — all carry with them more than just memories.
Our experiences, and those of our forebears, are never gone, even if they have been forgotten. They become a part of us, a molecular residue holding fast to our genetic scaffolding.
The DNA remains the same, but psychological and behavioral tendencies are inherited.
You might have inherited not just your grandmother’s knobby knees, but also her predisposition toward depression caused by the neglect she suffered as a newborn.
Or not. If your grandmother was adopted by nurturing parents, you might be enjoying the boost she received thanks to their love and support.
The mechanisms of behavioral epigenetics underlie not only deficits and weaknesses but strengths and resiliencies, too. And for those unlucky enough to descend from miserable or withholding grandparents, emerging drug treatments could reset not just mood, but the epigenetic changes themselves.
Methylation just gums up the works. So the less the better when it comes to transcribing the affected gene. In this case, methylation associated with miserable mothering prevented the normal number of glucocorticoid receptors from being transcribed in the baby’s hippocampus. And so for want of sufficient glucocorticoid receptors, the rats grew up to be nervous wrecks.
Mount Sinai study establishes mechanism by which an early window of exposure defines the response to stress in adulthood
#I’ve always bristled at being told “what doesn’t kill you will make you stronger”. With a chronic condition, this is absolutely NOT true.
Early life stress encodes lifelong susceptibility to stress through long-lasting transcriptional programming in a brain reward region implicated in mood and depression
The Mount Sinai study focuses on epigenetics, the study of changes in the action of genes caused not by changes in DNA code we inherit from our parents, but instead by molecules that regulate when, where, and what degree our genetic material is activated.
Such regulation derives, in part, from the function of transcription factors — specialized proteins that bind to specific DNA sequences in our genes and either encourage or shut down the expression of a given gene.
Previous studies in humans and animals have suggested that early life stress increases the risk for depression and other psychiatric syndromes, but the neurobiology linking the two has remained elusive until now.
“We discovered that disrupting maternal care of mice produces changes in levels of hundreds of genes in the VTA that primes this brain region to be in a depression-like state, even before we detect behavioral changes. Essentially, this brain region encodes a lifelong, latent susceptibility to depression that is revealed only after encountering additional stress.”
Specifically, Mount Sinai investigators identified a role for the developmental transcription factor orthodenticle homeobox 2 (Otx2) as a master regulator of these enduring gene changes.
The research team showed that baby mice that were stressed in a sensitive period (from postnatal day 10-20) had suppressed Otx2 in the VTA. While Otx2 levels ultimately recovered by adulthood, the suppression had already set in motion gene alterations that lasted into adulthood, indicating that early life stress disrupts age-specific developmental programming orchestrated by Otx2.
Furthermore, the mice stressed during the early-life sensitive time period were more likely to succumb to depression-like behavior in adulthood, but only after additional adult stress. All mice acted normally before additional adult social stress, but a “second hit” of stress was more likely to trigger depression-like behavior for mice stressed during the sensitive time period.
While early-life critical periods have been understood for processes such as language learning, little is known about whether there are sensitive periods in childhood when stress and adversity most impacts brain development and particularly emotion-regulation systems.
“The ultimate translational goal of this research is to aid treatment discoveries relevant to individuals who experienced childhood stress and trauma.”
The idea that organisms can stably inherit characteristics they acquire during their lifetimes was discarded a long time ago; the fact that it doesn’t seem to happen was a big strike against the pre-Darwinian idea about evolution. But over the last few decades, that idea has been making a bit of a comeback.
We’ve identified a few forms of epigenetic inheritance—primarily chemical modifications of DNA—that can be changed during the life of an organism but can still be passed down to its progeny.
There’s clear evidence that this sort of inheritance is used in plants, and there are a few hints that it could influence significant traits in animals.
Yesterday, Nature Neuroscience published a paper that provides the strongest evidence yet that an acquired trait can be passed down for several generations in mice.
Animals that were trained to associate a specific smell with pain produced progeny that also were sensitive to the smell—even when their entire role in producing the next generation was limited to being a sperm donor.
The authors chose their odorant (acetophenone) very carefully, because it was one where the receptor that perceives its presence had been identified. So they looked in the olfactory nerve cells and found that the sensitive mice had more neurons that expressed this receptor. In other words, the parental exposure and training seemed to prime offspring to be able to perceive the odor much more easily.
Looking at the gene itself, the authors found that the training process resulted in changes to the chemical modifications of the DNA nearby that were present in the sperm of the animals. (They also checked for changes in the proteins that package the DNA, but they found none.)
Thus, they conclude that epigenetic inheritance is indeed passing the fears of the father onto at least two generations of offspring.
Are these at the root of the Biblical sins of the father?
the initial results seem solid and very, very interesting
Our results delineate for the first time a transcriptomic signature in the prefrontal cortex resulting from peripheral injury six months prior. Interestingly, both coding and non-coding transcripts are altered.
Peripheral nerve injury is accompanied by chronic transcriptome-wide changes in the mouse prefrontal cortex
Peripheral nerve injury can have long-term consequences including pain-related manifestations, such as hypersensitivity to cutaneous stimuli, as well as affective and cognitive disturbances, suggesting the involvement of supraspinal mechanisms.
Changes in brain structure and cortical function associated with many chronic pain conditions have been reported in the prefrontal cortex (PFC).
The PFC is implicated in pain-related co-morbidities such as depression, anxiety and impaired emotional decision-making ability.
We recently reported that this region is subject to significant epigenetic reprogramming following peripheral nerve injury, and normalization of pain-related structural, functional and epigenetic abnormalities in the PFC are all associated with effective pain reduction.
hypothesis that peripheral nerve injury triggers persistent long-lasting changes in gene expression in the PFC, which alter functional gene networks, thus providing a possible explanation for chronic pain associated behaviors.
Genes involved in chronic injury and altered neuronal growth and proliferation in the PFC
Significantly altered biological processes included neurological disease, skeletal muscular disorders, behavior, and psychological disorders.
Several of the changes detected by RNAseq were validated by RT-QPCR and included transcripts with known roles in chronic pain and/or neuronal plasticity including the NMDA receptor (glutamate receptor, ionotropic, NMDA; grin1), neurite outgrowth (roundabout 3; robo3), gliosis (glial fibrillary acidic protein; gfap), vesicular release (synaptotagmin 2; syt2), and neuronal excitability (voltage-gated sodium channel, type I; scn1a).
Peripheral injury is accompanied by behavioral signs of neuropathic pain six months post-injury
Mutations in sodium channels have been previously implicated in pain and in the modulation of neuropathic and inflammatory pain
Peripheral injury is accompanied transcriptomic changes in the prefrontal cortex six months post-injury
This is the first demonstration of long-term overexpression of scn1a in the prefrontal cortex following peripheral injury.
One of the functional gene pathways that is highly enriched by genes that are differentially expressed six months after nerve injury is the pathway involved in nervous system development and functions
Molecular transport and neurological disease
Chronic pain changes the brain at various levels:
- cortical grey matter,
- white matter, and
- overall cortical excitability
have all been reported
Nervous system development and function
We demonstrate broad changes in gene expression in the mouse prefrontal cortex six months after peripheral nerve injury, illustrating a long-term impact of a peripheral injury on brain genome function
Noradrenaline goes nuclear: epigenetic modifications during long-lasting synaptic potentiation triggered by activation of β-adrenergic receptors – Maity – Dec 2015 – The Journal of Physiology – Wiley Online Library
- Transcription is recruited by noradrenaline in the hippocampus.
- Epigenetic mechanisms are recruited by hippocampal noradrenergic receptor activation.
- Epigenetic regulation by noradrenaline offers a novel mechanism for long-term potentiation
Noradrenaline (NA) is a neuromodulator that can effect long-lasting changes in synaptic strengthsuch as long-term potentiation (LTP), a putative cellular mechanism for memory formation in the mammalian brain
Persistent LTP requires alterations in gene expression that may involve epigenetic mechanisms such as DNA methylation, histone acetylation and histone phosphorylation.
It is known that β-adrenergic receptors and NA can boost LTP maintenance by regulating translation. However, it is unclear whether NA can additionally engage epigenetic mechanisms to regulate transcription and boost LTP endurance
To address this issue, we probed NA-treated mouse hippocampal slices with pharmacological inhibitors targeting epigenetic regulatory pathways and discovered that NA activates β-adrenergic receptors to boost LTP maintenance in area CA1 through DNA methylation and post-translational histone modifications.
Specifically, NA paired with 100 Hz stimulation enhanced histone H3 acetylation and phosphorylation, both of which were required for NA-induced boosting of LTP maintenance
Together, our findings identify NA as a neuromodulatory transmitter capable of triggering epigenetic, transcriptional control of genes required for establishing persistent LTP in the mouse hippocampus
These modifications may contribute to the stabilization of memory.