DNA modifications measured in blood signal related changes in the brain

Johns Hopkins researchers say they have confirmed suspicions that DNA modifications found in the blood of mice exposed to high levels of stress hormone—and showing signs of anxiety—are directly related to changes found in their brain tissues.

The proof-of-concept study, reported online ahead of print in the June issue of Psychoneuroendocrinology, offers what the research team calls the first evidence that epigenetic changes that alter the way genes function without changing their underlying DNA sequence—and are detectable in —mirror alterations in tissue linked to underlying psychiatric diseases.

The new study reports only on so-called epigenetic changes to a single stress response gene called FKBP5, which has been implicated in depression, bipolar disorder and . But the researchers say they have discovered the same blood and brain matches in dozens more genes, which regulate many important processes in the brain.

"Many human studies rely on the assumption that disease-relevant epigenetic changes that occur in the brain—which is largely inaccessible and difficult to test—also occur in the blood, which is easily accessible," says study leader Richard S. Lee, Ph.D., an instructor in the Department of Psychiatry and Behavioral Sciences at the Johns Hopkins University School of Medicine. "This research on mice suggests that the blood can legitimately tell us what is going on in the brain, which is something we were just assuming before, and could lead us to better detection and treatment of mental disorders and for a more empirical way to test whether medications are working."

For the study, the Johns Hopkins team worked with mice with a rodent version of Cushing's disease, which is marked by the overproduction and release of cortisol, the primary stress hormone also called glucocorticoid. For four weeks, the mice were given different doses of in their drinking water to assess epigenetic changes to FKBP5. The researchers took blood samples weekly to measure the changes and then dissected the brains at the end of the month to study what changes were occurring in the hippocampus as a result of glucocorticoid exposure. The hippocampus, in both mice and humans, is vital to memory formation, information storage and organizational abilities.

The measurements showed that the more stress hormones the mice got, the greater the epigenetic changes in the blood and brain tissue, although the scientists say the brain changes occurred in a different part of the gene than expected. This was what made finding the blood-brain connection very challenging, Lee says.

Also, the more stress hormone, the more RNA from the FKBP5 gene was expressed in the blood and brain, and the greater the association with depression. However, it was the underlying epigenetic changes that proved to be more robust. This is important, because while RNA levels may return to normal after decrease or change due to small fluctuations in , persist, reflect overall stress hormone exposure and predict how much RNA will be made when stress hormone levels increase.

The team of researchers used an epigenetic assay previously developed in their laboratory that requires just one drop of blood to accurately assess overall exposure to stress hormone over 30 days. Elevated levels of stress hormone exposure are considered a risk factor for mental illness in humans and other mammals.

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Journal information: Psychoneuroendocrinology

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Apr 09, 2014
Now that this technique has been confirmed empirically there may be more (properly funded) cross-disciplinary research opportunities correlating epigenetic changes with brain pathology with the enticing prospect of remotely diagnosing a range of neurological conditions.

Apr 09, 2014
"...variations in the FKBP5 gene contribute to the development of opiate addiction by modulating the stress response." http://www.scienc...14001139

Now that the epigenetic landscape has been linked to the physical landscape of DNA via SNPs linked to behavior, evolutionary theorists may begin to understand why attempts have failed to link mutation-initiated natural selection to species diversity.

It has become perfectly clear that the conserved molecular mechanisms of nutrient stress and social stress epigenetically effect the hormones that affect behavior in vertebrates and invertebrates. That suggests a pattern across a continuum of ecological variations that typically result in ecological adaptations.

If you are surprised to learn about the link from ecological variation to adaptations manifested in DNA modifications found in the blood and cell type differentiation in the brain, you should learn something about molecular epigenetics.

Apr 13, 2014
Close. Original DNA sequence is replaced with the same sequence (repaired after damage) and will then be expressed by the same gene differently. The change in expression is now heritable.
For all cells, no exceptions.
Unfortunately, the focus has always been on the outcomes of faulty repair. Too bad.

All this time so close, yet only a tad off.

Apr 13, 2014
Homework assignment:
Allotted time to solve - till tomorrow.
How can this repair, implementing the exact same sequence, be read differently after repair?

Answer pending - see above.

Apr 13, 2014
Cryptic nonsense.

Stop pretending to know anything about this fact: Nutrients facilitate DNA repair, which is manifested in the amino acid substitutions that stabilize the genome.

The fixation of the substitutions exemplifies the difference between theories that involve mutations and biological facts that show mutations are not fixed in the organized genome of any species.

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