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

Moon, HY; Becke, A; Berron, D; Becker, B; Sah, N; Benoni, G; Janke, E; ... van Praag, H; + view all (2016) Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function. Cell Metabolism , 24 (2) pp. 332-340. 10.1016/j.cmet.2016.05.025. Green open access

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Abstract

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 the cognitive and neurogenic 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. Furthermore, recombinant CTSB application enhanced expression of brain-derived neurotrophic factor (BDNF) and doublecortin (DCX) in adult hippocampal progenitor cells through a mechanism dependent on the multifunctional protein P11. In vivo, in CTSB knockout (KO) mice, running did not enhance adult hippocampal neurogenesis and spatial memory function. Interestingly, in Rhesus monkeys and humans, treadmill exercise elevated CTSB in plasma. In humans, changes in CTSB levels correlated with fitness and hippocampus-dependent memory function. Our findings suggest CTSB as a mediator of effects of exercise on cognition.

Type: Article
Title: Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.cmet.2016.05.025
Publisher version: http://doi.org/10.1016/j.cmet.2016.05.025
Language: English
Additional information: Published by Elsevier Inc. This manuscript version is made available under a Creative Commons Attribution Non-commercial Non-derivative 4.0 International license (CC BY-NC-ND 4.0). This license allows you to share, copy, distribute and transmit the work for personal and non-commercial use providing author and publisher attribution is clearly stated. Further details about CC BY licenses are available at http://creativecommons.org/ licenses/by/4.0. Access may be initially restricted by the publisher.
Keywords: Cathepsin B, exercise, hippocampus, humans, memory, mice, muscle
UCL classification: UCL
UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Div of Psychology and Lang Sciences > Institute of Cognitive Neuroscience
URI: https://discovery.ucl.ac.uk/id/eprint/1503642
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