Exercise Promotes Cathepsin B Expression, Neurogenesis, and Memory Function

Researchers have recently investigated one of the numerous mechanisms by which regular exercise acts to improve brain function over the long term. In this case, there is a chain of interactions that leads via cathepsin B to the better known brain-derived neurotrophic factor (BDNF) that then boosts neurogenesis, the creation of new brain cells. Neurogenesis declines in adult life, but is essential to neural plasticity, the ability of the brain to adapt and, to a limited degree, heal itself. Cathepsin B is also involved in lysosomal function, a part of the cellular maintenance systems responsible for clearing out damaged proteins and cell structures. Down that path, if you look back in the Fight Aging! archives, you'll find an interesting study on increased cathepsin B levels in flies, in which improved lysosomal function cleared more unwanted cellular debris as a result.

A protein called cathepsin B, produced and secreted by muscle during exercise, is required for exercise-induced memory improvement and brain cell production in mice. Researchers also showed that levels of cathepsin B are positively correlated with fitness and memory in humans. "This is a super exciting area. Exercise has so many health benefits, yet we know so little about many of these effects at a molecular level. This paper provides a convincing mechanism that involves running-induced increases in a particular protein - cathepsin B - that appears to promote neurogenesis by enhancing expression of a growth factor - BDNF - in the brain. This is a long chain of events, from exercise to muscle to brain to cognition, but the authors do a great job at demonstrating each of the links."

Running has been shown in animals to have a variety of effects on the brain, including enhanced memory function and increased production of new brain cells (neurogenesis). In humans, a correlation between exercise and memory function has also been observed. But how muscle activity might be mechanistically linked to memory has been somewhat of a mystery. To hunt for mucle-produced factors called myokines that might modulate brain function, researchers treated rat muscle cells in culture with the drug AICAR - "an exercise mimetic," meaning it boosts the cells' metabolic activities. Among the proteins upregulated in the treated cells was a secreted factor, small enough to traverse the blood-brain barrier, that had previously been shown to be upregulated in muscle during exercise: cathepsin B.

In mice that exercised for two to four weeks, plasma levels of cathepsin B were significantly increased, and the animals showed improved memory as well as increased neurogenesis in their hippocampi - a brain region involved in learning and memory. Mice that were genetically engineered to lack cathepsin B, on the other hand, did not show these exercise-related effects. The team also showed that cathepsin B treatment of murine adult hippocampal progenitor cells in culture induced the expression of two key nerve growth factors - brain-derived neurotrophic factor (BDNF) and doublecortin - which may explain how the myokine induces neurogenesis. In rhesus monkeys and humans, four months of treadmill training increased blood levels of cathepsin B, the team showed, and this increase was correlated with improved memory recall in the human study participants.

Link: http://www.the-scientist.com/?articles.view/articleNo/46397/title/Exercise-Induced-Muscle-Factor-Promotes-Memory/

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