Introducing the brain; increased exercise reprograms (Introduction)

by David Turell @, Tuesday, November 06, 2018, 18:26 (40 days ago) @ dhw

Rodent research makes the point that mental ability is increased by vigorous exercise:

"Researchers have long recognized that exercise sharpens certain cognitive skills. Indeed, Maejima and his colleagues have found that regular physical activity improves mice’s ability to distinguish new objects from ones they’ve seen before. Over the past 20 years, researchers have begun to get at the root of these benefits, with studies pointing to increases in the volume of the hippocampus, development of new neurons, and infiltration of blood vessels into the brain. Now, Maejima and others are starting to home in on the epigenetic mechanisms that drive the neurological changes brought on by physical activity.

'In October, Maejima’s team reported that the brains of rodents that ran had greater than normal histone acetylation in the hippocampus, the brain region considered the seat of learning and memory.1 ,The epigenetic marks resulted in higher expression of Bdnf, the gene for brain-derived neurotrophic factor (BDNF). By supporting the growth and maturation of new nerve cells, BDNF is thought to promote brain health, and higher levels of it correlate with improved cognitive performance in mice and humans.

"Over the past two decades, researchers have identified many molecular mechanisms underlying exercise’s influence on cognition. Exercise, studies have shown, leads to the release of proteins and other molecules from muscle, fat, and liver tissue that can affect levels of BDNF and other agents that spur neurogenesis, speed new-neuron maturation, promote brain vascularization, and even increase the volume of the hippocampus in humans.


"Exercise influences levels of neurotrophins, proteins that promote the proliferation of neurons and support their function. Physical activity enhances DNA demethylation in the promoter region of the Bdnf gene, increasing the expression of the neurogenesis-boosting signaling factor. Moreover, histone acetylation appears to loosen chromatin to bolster Bdnf transcription.

"Exercise leads to the secretion of molecules by muscle and fat cells that affect levels of growth factors in the brain, influencing the shape and function of the hippocampus by accelerating new neuron growth and increasing the volume of the brain region.

"In the sperm of male mice that exercise, the abundance of certain microRNAs associated with learning and memory increases. The mice’s offspring show slight cognitive advantages compared with offspring of sedentary mice.


"Since Reul’s study, at least two dozen others have reported acetylation and other epigenetic changes that link exercise to the brain in rodents. Moses Chao, a molecular neurobiologist at the New York University School of Medicine, and colleagues recently found that mice that ran frequently on wheels had higher levels of BDNF and of a ketone that’s a byproduct of fat metabolism released from the liver. Injecting the ketone into the brains of mice that did not run helped to inhibit histone deacetylases and increased Bdnf expression in the hippocampus. The finding shows how molecules can travel through the blood, cross the blood-brain barrier, and activate or inhibit epigenetic markers in the brain.

"While some researchers probe the epigenetic connection between exercise and cognitive prowess, others continue to unveil previously unknown links. In 2016, for example, van Praag, now at the Florida Atlantic University Brain Institute, and colleagues found that a protein called cathepsin B, which is secreted by muscle cells during physical activity, was required for exercise to spur neurogenesis in mice. In tissue cultures of adult hippocampal neural progenitor cells, cathepsin B boosted the expression of Bdnf and the levels of its protein and enhanced the expression of a gene called doublecortin (DCX), which encodes a protein needed for neural migration. Cathepsin B knockout mice had no change in neurogenesis following exercise.


"Van Praag’s team also found that nonhuman primates and humans who ran on treadmills had elevated blood serum levels of cathepsin B after exercising. Following four months of running on the treadmill three days per week for 45 minutes or more, participants drew more-accurate pictures from memory than at the beginning of the study, before they started exercising.


"Since the 1980s, studies of humans have pointed to a link between exercise and gains in cognitive performance. Understanding this relationship is of particular importance to patients with neurological diseases. University of Southern California neuroscientist Giselle Petzinger has been treating patients with Parkinson’s disease for decades and has observed that those who exercise can improve their balance and gait. Such an observation hinted that the brain retains some plasticity after disease symptoms set in, she says, with neural connections forming to support the gains in motor skills."

Comment: From our knowledge of human evolution through a stage of hunter-gatherers, who had lots of exercise and a large brain they needed to learn to use, this connection makes lots of sense.

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