title: Running-Induced Systemic Cathepsin B Secretion Is Associated with Memory Function.
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.
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA.
authors.forename: Hyo Youl
authors.initials: HY
authors.lastname: Moon
authors.affiliation: Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Becke
authors.affiliation: Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Berron
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Becker
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA.
authors.forename: Nirnath
authors.initials: N
authors.lastname: Sah
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA.
authors.forename: Galit
authors.initials: G
authors.lastname: Benoni
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA.
authors.forename: Emma
authors.initials: E
authors.lastname: Janke
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA.
authors.forename: Susan T
authors.initials: ST
authors.lastname: Lubejko
authors.affiliation: Drug Design and Development Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA.
authors.forename: Nigel H
authors.initials: NH
authors.lastname: Greig
authors.affiliation: Non-human Primate Core, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD 21224, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Mattison
authors.affiliation: Institute of Cognitive Neurology and Dementia Research, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Emrah
authors.initials: E
authors.lastname: Duzel
authors.affiliation: Neuroplasticity and Behavior Unit, Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD 21224, USA. Electronic address: vanpraag17@gmail.com.
authors.forename: Henriette
authors.initials: H
authors.lastname: van Praag
mesh_terms: D000328:Adult; D000339:Affect; D000375:Aging / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D002401:Cathepsin B / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D003071:Cognition; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D005080:Exercise Test; D005260:Female; D006624:Hippocampus / Q000502:physiology; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D008568:Memory / Q000502:physiology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009043:Motor Activity; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism; D010805:Physical Conditioning, Animal; D015203:Reproducibility of Results; D012420:Running / Q000502:physiology*; D057185:Sedentary Behavior; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C000714328:DCX protein, human; C000714847:Dcx protein, mouse; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D002401:Cathepsin B
keywords: cathepsin B; exercise; hippocampus; humans; memory; mice; muscle