title: Retroviral induction of GSK-3β expression blocks the stimulatory action of physical exercise on the maturation of newborn neurons.
abstract: Adult hippocampal neurogenesis (AHN) is a key process for certain types of hippocampal-dependent learning. Alzheimer's disease (AD) is accompanied by memory deficits related to alterations in AHN. Given that the increased activity of GSK-3β has been related to alterations in the population of hippocampal granule neurons in AD patients, we designed a novel methodology by which to induce selective GSK-3β overexpression exclusively in newborn granule neurons. To this end, we injected an rtTA-IRES-EGFP-expressing retrovirus into the hippocampus of tTO-GSK-3β mice. Using this novel retroviral strategy, we found that GSK-3β caused a cell-autonomous impairment of the morphological and synaptic maturation of newborn neurons. In addition, we examined whether GSK-3β overexpression in newborn neurons limits the effects of physical activity. While physical exercise increased the number of dendritic spines, the percentage of mushroom spines, and the head diameter of the same in tet-OFF cells, these effects were not triggered in tet-ON cells. This observation suggests that GSK-3β blocks the stimulatory actions of exercise. Given that the activity of GSK-3β is increased in the brains of individuals with AD, these data may be relevant for non-pharmacological therapies for AD.
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, c/Nicolás Cabrera 1, 28049, Madrid, Spain. m.llorens@csic.es.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), c/Valderrebollo 5, Madrid, Spain. m.llorens@csic.es.
authors.forename: María
authors.initials: M
authors.lastname: Llorens-Martín
authors.affiliation: Emotional Brain Institute, Nathan Kline Institute, New York, NY, USA.
authors.forename: Catia M
authors.initials: CM
authors.lastname: Teixeira
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, c/Nicolás Cabrera 1, 28049, Madrid, Spain.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), c/Valderrebollo 5, Madrid, Spain.
authors.forename: Jerónimo
authors.initials: J
authors.lastname: Jurado-Arjona
authors.affiliation: Faculty of Health and Sport Sciences and Tsukuba International Academy for Sport Studies (TIAS), University of Tsukuba, Tsukuba, Ibaraki, 305-8574, Japan.|Global Research Center for Innovative Life Science, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Shinagawa, Tokyo, 142-8501, Japan.
authors.forename: Randeep
authors.initials: R
authors.lastname: Rakwal
authors.affiliation: Global Research Center for Innovative Life Science, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, Shinagawa, Tokyo, 142-8501, Japan.|Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8574, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Shibato
authors.affiliation: Laboratory of Exercise Biochemistry and Neuroendocrinology, Faculty of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki, 305-8574, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Soya
authors.affiliation: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, c/Nicolás Cabrera 1, 28049, Madrid, Spain. javila@cbm.csic.es.|Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, ISCIII), c/Valderrebollo 5, Madrid, Spain. javila@cbm.csic.es.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ávila
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism / Q000473:pathology; D005260:Female; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D055495:Neurogenesis; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D012190:Retroviridae / Q000235:genetics; D013131:Spine / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta
keywords: Adult neurogenesis; GSK-3β; Hippocampus; Physical exercise; Retrovirus; rtTA