title: Differential proteomic and behavioral effects of long-term voluntary exercise in wild-type and APP-overexpressing transgenics.
abstract: Physical exercise may provide protection against the cognitive decline and neuropathology associated with Alzheimer's disease, although the mechanisms are not clear. In the present study, APP/PSEN1 double-transgenic and wild-type mice were allowed unlimited voluntary exercise for 7months. Consistent with previous reports, wheel-running improved cognition in the double-transgenic mice. Interestingly, the average daily distance run was strongly correlated with spatial memory in the water maze in wild-type mice (r(2)=.959), but uncorrelated in transgenics (r(2)=.013). Proteomics analysis showed that sedentary transgenic mice differed significantly from sedentary wild-types with respect to proteins involved in synaptic transmission, cytoskeletal regulation, and neurogenesis. When given an opportunity to exercise, the transgenics' deficiencies in cytoskeletal regulation and neurogenesis largely normalized, but abnormal synaptic proteins did not change. In contrast, exercise enhanced proteins associated with cytoskeletal regulation, oxidative phosphorylation, and synaptic transmission in wild-type mice. Soluble and insoluble Aβ40 and Aβ42 levels were significantly decreased in both cortex and hippocampus of active transgenics, suggesting that this may have played a role in the cognitive improvement in APP/PSEN1 mice. β-secretase was significantly reduced in active APP/PSEN1 mice compared to sedentary controls, suggesting a mechanism for reduced Aβ. Taken together, these data illustrate that exercise improves memory in wild-type and APP-overexpressing mice in fundamentally different ways.
authors.affiliation: Departments of Neurology and Anatomy & Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Shailaja Kishan
authors.initials: SK
authors.lastname: Rao
authors.affiliation: Departments of Neurology and Anatomy & Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Ross
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN 37204, USA; Program in Neuroscience, Vanderbilt University, Nashville, TN 37204, USA.
authors.forename: Fiona E
authors.initials: FE
authors.lastname: Harrison
authors.affiliation: Program in Neuroscience, Vanderbilt University, Nashville, TN 37204, USA; Institute of Neurobiology, Medical Sciences Campus University of Puerto Rico, Old San Juan, PR 00901, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Bernardo
authors.affiliation: Program in Neuroscience, Vanderbilt University, Nashville, TN 37204, USA.
authors.forename: Randall S
authors.initials: RS
authors.lastname: Reiserer
authors.affiliation: Vanderbilt Institute for Integrative Biosystems Research and Education, Vanderbilt University, Nashville, TN 37204, USA.
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Reiserer
authors.affiliation: Department of Surgery, University of Alabama, Birmingham, AL 35294, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Mobley
authors.affiliation: Departments of Neurology and Anatomy & Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38163, USA. Electronic address: mike@tennessee.edu.
authors.forename: Michael P
authors.initials: MP
authors.lastname: McDonald
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000523:psychology; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism; D001522:Behavior, Animal; D006624:Hippocampus / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity; D053764:Presenilin-1 / Q000235:genetics / Q000378:metabolism; D040901:Proteomics; D065852:Spatial Memory / Q000502:physiology*
chemical_list: D016564:Amyloid beta-Protein Precursor; C508853:PSEN1 protein, human; D053764:Presenilin-1; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509282:Bace1 protein, mouse
keywords: Alzheimer's disease; Amyloid; Behavior; Cognition; Exercise; Memory
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