Scientists discover 'fickle' DNA changes in brain
Johns Hopkins scientists investigating chemical modifications across the genomes of adult mice have discovered that DNA modifications in non-dividing brain cells, thought to be inherently stable, instead underwent large-scale dynamic changes as a result of stimulated brain activity. Their report, in the October issue of Nature Neuroscience, has major implications for treating psychiatric diseases, neurodegenerative disorders, and for better understanding learning, memory and mood regulation.
Specifically, the researchers, who include a husband-and-wife team, found evidence of an epigenetic change called demethylation the loss of a methyl group from specific locations in the non-dividing brain cells' DNA, challenging the scientific dogma that even if the DNA in non-dividing adult neurons changes on occasion from methylated to demethylated state, it does so very infrequently.
"We provide definitive evidence suggesting that DNA demethylation happens in non-dividing neurons, and it happens on a large scale," says Hongjun Song, Ph.D., professor of neurology and neuroscience and director of the Stem Cell Program in the Institute for Cell Engineering of the Johns Hopkins University School of Medicine. "Scientists have previously underestimated how important this epigenetic mechanism can be in the adult brain, and the scope of change is dramatic."
DNA comprises the fixed chemical building blocks of each person or animal's genome, but the addition or removal of a methyl group at the specific location chemically alters DNA and regulates gene expression, enabling cells with the same genetic code to acquire and activate separate functions.
In previously published work, the same Hopkins researchers reported that electrical brain stimulation, such as that used in electroconvulsive therapy (ECT) for patients with drug resistant depression, resulted in increased brain cell growth in mice, due likely to changes in DNA methylation status.
This time, they again used electric shock to stimulate the brains of live mice. A few hours after administering the brain stimulation, the scientists analyzed two million of the same type of neurons from the brains of stimulated mice, focusing on what happens to one building block of DNA cytosine at 219,991 sites. These sites represented about one percent of all cytosines in the whole mouse genomes.
In collaboration with genomic biologist Yuan Gao, now at the Lieber Institute for Brain Development, the scientists used the latest DNA sequencing technology and compared neurons in mice with or without brain stimulation. About 1.4 percent of the cytosines measured showed rapid active demethylation or became newly methylated.
"It was mind-boggling to see that so many methylation sites thousands of sites had changed in status as a result of brain activity," Song says. "We used to think that the brain's epigenetic DNA methylation landscape was as stable as mountains and more recently realized that maybe it was a bit more subject to change, perhaps like trees occasionally bent in a storm. But now we show it is most of all like a river that reacts to storms of activity by moving and changing fast."
The majority of the sites where the methylation status of the cytosine changed as a result of the brain activity were not in the expected areas of the genome that are traditionally believed to control gene expression, Song notes. Rather, they were in regions where cytosines are low in density, in genomic regions where the function of DNA methylation is not well understood.
Because DNA demethylation can occur passively during cell division, the scientists targeted radiation to the sections of mouse brains they were studying, permanently preventing passive cell division, and still found evidence of DNA demethylation. This confirms, they say, that the DNA methylation changes they measured occurred independently of cell division.
"Our finding opens up new opportunities to figure out if these epigenetic modifications are potential drug targets for treating depression and promote regeneration, for instance," says Guo-li Ming, M.D., Ph.D., professor of neurology and neuroscience.
Provided by Johns Hopkins Medical Institutions
- Hopkins team discovers how DNA changes Apr 14, 2011 | not rated yet | 0
- Growth of new brain cells requires 'epigenetic' switch Jan 08, 2009 | not rated yet | 0
- Researchers identify new mechanism used by cells to reverse silenced genes Jun 30, 2011 | not rated yet | 0
- Study identifies a protein complex possibly crucial for triggering embryo development Jan 06, 2010 | not rated yet | 0
- Gene switch sites found mainly on 'shores,' not just 'islands' of the human genome Jan 18, 2009 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
Alcohol and acetaminophen
May 13, 2013 Edit: sorry for the typo in the title , can't edit I looked around on google quite a bit and it's very hard to find precise information on the...
Marie Curie's leukemia
May 13, 2013 Does anyone know what might be the cause of Marie Curie's cancer
- More from Physics Forums - Medical Sciences
More news stories
For combat veterans suffering from post-traumatic stress disorder, 'fear circuitry' in the brain never rests
Chronic trauma can inflict lasting damage to brain regions associated with fear and anxiety. Previous imaging studies of people with post-traumatic stress disorder, or PTSD, have shown that these brain regions can over-or ...
Neuroscience May 18, 2013 | 5 / 5 (1) | 0 |
The neural machinery underlying our olfactory sense continues to be an enigma for neuroscience. A recent review in Neuron seeks to expand traditional ideas about how neurons in the olfactory bulb might encode information about ...
Neuroscience May 17, 2013 | 4 / 5 (1) | 0 |
(Medical Xpress)—What if the quality of your work depends more on your focus on the piano keys or canvas or laptop than your musical or painting or computing skills? If target users can be convinced, they ...
Neuroscience May 17, 2013 | 3.7 / 5 (3) | 0 |
Neurological disorders can have a devastating impact on the lives of sufferers and their families.
Neuroscience May 17, 2013 | 5 / 5 (1) | 0 |
If you're a left-brain thinker, chances are you use your right hand to hold your cell phone up to your right ear, according to a newly published study from Henry Ford Hospital in Detroit.
Neuroscience May 16, 2013 | 2 / 5 (2) | 0 |
Scientists at Johns Hopkins have turned their view of osteoarthritis (OA) inside out. Literally. Instead of seeing the painful degenerative disease as a problem primarily of the cartilage that cushions joints, ...
13 hours ago | 4.8 / 5 (5) | 0 |
In their quest to learn more about the variability of cells between and within tissues, biomedical scientists have devised tools capable of simultaneously measuring dozens of characteristics of individual ...
13 hours ago | 5 / 5 (3) | 0 |
Researchers at the University of Wisconsin have identified a potential new risk factor for obstructive sleep apnea: asthma. Using data from the National Institutes of Health (Heart, Lung, and Blood Institute)-funded Wisconsin ...
12 hours ago | 5 / 5 (1) | 0 |
A new study looking at sleep-disordered breathing (SDB) and markers for Alzheimer's disease (AD) risk in cerebrospinal fluid (CSF) and neuroimaging adds to the growing body of research linking the two.
12 hours ago | 5 / 5 (2) | 0 |
The hunt for an HIV vaccine has gobbled up $8 billion in the past decade, and the failure of the most recent efficacy trial has delivered yet another setback to 26 years of efforts.
16 hours ago | not rated yet | 0
Gourmands and foodies everywhere have long recognized ginger as a great way to add a little peppery zing to both sweet and savory dishes; now, a study from researchers at Columbia University shows purified components of the ...
12 hours ago | 5 / 5 (1) | 0