Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function

Abstract

SUMMARY Peripheral processes that mediate beneficial effects of exercise on the brain remain sparsely explored. Here we show that a muscle secretory factor, Cathepsin B (CTSB) protein, is important for cognitive benefits of running. Proteomic analysis revealed elevated levels of CTSB in conditioned medium derived from skeletal muscle cell cultures treated with AMP-kinase agonist AICAR. Consistently, running increased CTSB levels in mouse gastrocnemius muscle and plasma. In addition, in male wildtype (WT), but not CTSB knockout (KO) mice running enhanced adult hippocampal neurogenesis and spatial memory. Furthermore, recombinant CTSB application enhanced expression of brain-derived neurotrophic factor (BDNF) and doublecortin (DCX) in adult hippocampal progenitor cells through a multifunctional protein, P11, dependent mechanism. Interestingly, in Rhesus monkeys and humans treadmill exercise elevated CTSB in plasma. In humans CTSB levels correlated with fitness and hippocampus-dependent memory function. Our findings suggest CTSB as a mediator of effects of exercise on cognition.

Intermittent metabolic switching, neuroplasticity and brain health

“…However, it remains to be determined whether irisin is particularly important in the enhancement of neuroplasticity and stress resistance conferred by IMS. A recent study provided evidence that the enzyme cathepsin B is an exercise-induced peripheral signal that contributes to the cognitive benefits of exercise 105 . Best known for its role as a lysosomal protease, plasma cathepsin B levels are increased in response to exercise in mice, monkeys and humans, and circulating cathepsin B levels are positively correlated with aerobic fitness and recall memory in humans 105 .…”

Muscle as a paracrine and endocrine organ

“…Endurance exercise increases the levels of circulating irisin which induces the expression of FNDC5 in the hippocampus that in turn promotes the expression of BDNF and thus neurogenesis[47]. Exercise also leads to elevated plasma levels of the myokine cathepsin-B (CTSB), which promotes BDNF expression in the hippocampus, promotes neurogenesis and increases spatial memory abilities [48]. While correlations were found between patient CTSB levels, fitness, and hippocampus-dependent memory functions, the extent to which this myokine is causative for the beneficial effects of physical activity on cognitive abilities remains to be determined.…”

A trip to brain for better performance in mathematics

“…It is over expressed in various cancers. Recently, Cathepsin B protein expression has been found to be upregulated in muscle and blood of mice, monkey and human after doing exercise [Moon HY et al, 2016]. Cathepsin B can cross blood-brain barrier and can increase the expression of molecules important for neurogenesis.…”