We all know that exercise is important for a strong and healthy body. Less appreciated is that exercise seems also to be important for a strong and healthy mind, boosting memory and learning, while possibly delaying age-related cognitive decline . How is this so? Researchers have assembled a growing body of evidence that suggests skeletal muscle cells secrete proteins and other factors into the blood during exercise that have a regenerative effect on the brain.
Now, an NIH-supported study has identified a new biochemical candidate to help explore the muscle-brain connection: a protein secreted by skeletal muscle cells called cathepsin B. The study found that levels of this protein rise in the blood of people who exercise regularly, in this case running on a treadmill. In mice, brain cells treated with the protein also exhibited molecular changes associated with the production of new neurons. Interestingly, the researchers found that the memory boost normally provided by exercise is diminished in mice unable to produce cathepsin B.
Caption: DNA (blue) loops around nucleosomes (gray) and is bound by transcription factors (red), proteins that switch genes on and off and act in a tissue-specific manner. When cells die, enzymes (scissors) chop up areas between the nucleosomes and transcription factors, releasing DNA fragments in unique patterns. By gathering the released DNA fragments in blood, researchers can tell which types of cells produced them. Credit: Shendure Lab/University of Washington
When cells die, scissor-like enzymes snip their DNA into tiny fragments that leak into the bloodstream and other bodily fluids. Researchers have been busy in recent years working on ways to collect these free-floating bits of DNA and explore their potential use in clinical care.
These approaches, sometimes referred to as “liquid biopsies,” hinge on the ability to distinguish specific DNA fragments from the body’s normal background of “cell-free” DNA, most of which comes from dying white blood cells. Seeking other sources for cell-free DNA in particular situations is beginning to bear fruit, however. Current applications include: 1) a test in maternal blood to look for DNA from the fetus (actually from the fetal component of the placenta), which provides a means of detecting a possible genetic abnormality; 2) a test in a cancer patient’s blood to look for cancer-specific mutations, as a way of assessing response to treatment or early signs of relapse; and 3) a test in an organ transplant recipient, where increasing abundance of DNA fragments from the donor can be an early sign of rejection.
But recent proposals have been floated about looking for cell-free DNA in healthy individuals, as an early sign of some health problems. Suppose something was found—how could you know the source? Now a team of NIH-funded researchers has devised a new method that uses distinctive features of DNA packaging to provide an additional layer of information about the origins of free-floating DNA, vastly expanding the potential uses for such tests .
COOL TOOL. See how the TALE protein (rainbow colored) recognizes the target DNA site and wraps around the double helix. When this TALE protein is fused to a nuclease (the scissors), creating a TALEN, the hybrid protein will clip the DNA at the target site. Credit: Jeffry D. Sander, Massachusetts General Hospital
If I made a spelling mistake in this blog, and you were my copy editor, you’d want to fix it quickly. You’d delete the wrong letter and insert the correct one. Well, DNA is a language too, with just four letters in its alphabet; and disease can occur with just one letter out of place if it’s in a vulnerable position (think sickle cell anemia or the premature aging disease, progeria). Wouldn’t it be great for tomorrow’s physicians to be able to do what the copy editor does? That is, if they could fix a genetic mutation quickly and efficiently, without messing up the rest of the text?