title: Exercise during pregnancy mitigates Alzheimer-like pathology in mouse offspring.
abstract: Physical activity protects brain function in healthy individuals and those with Alzheimer's disease (AD). Evidence for beneficial effects of parental exercise on the health status of their progeny is sparse and limited to nondiseased individuals. Here, we questioned whether maternal running interferes with offspring's AD-like pathology and sought to decipher the underlying mechanisms in TgCRND8 mice. Maternal stimulation was provided by voluntary wheel running vs. standard housing during pregnancy. Following 5 mo of standard housing of transgenic and wild-type offspring, their brains were examined for AD-related pathology and/or plasticity changes. Running during pregnancy reduced β-amyloid (Aβ) plaque burden (-35%, P=0.017) and amyloidogenic APP processing in transgenic offspring and further improved the neurovascular function by orchestrating different Aβ transporters and increasing angiogenesis (+29%, P=0.022). This effect was accompanied by diminished inflammation, as indicated by reduced microgliosis (-20%, P=0.002) and down-regulation of other proinflammatory mediators, and resulted in less oxidative stress, as nitrotyrosine levels declined (-28%, P=0.029). Moreover, plasticity changes (in terms of up-regulation of reelin, synaptophysin, and ARC) were found not only in transgenic but also in wild-type offspring. We conclude that exercise during pregnancy provides long-lasting protection from neurodegeneration and improves brain plasticity in the otherwise unstimulated progeny.
authors.affiliation: Institute of Pathology and Neuropathology, University Hospital Essen, Essen, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Herring
authors.forename: Anja
authors.initials: A
authors.lastname: Donath
authors.forename: Maksym
authors.initials: M
authors.lastname: Yarmolenko
authors.forename: Ellen
authors.initials: E
authors.lastname: Uslar
authors.forename: Catharina
authors.initials: C
authors.lastname: Conzen
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Kanakis
authors.forename: Claudius
authors.initials: C
authors.lastname: Bosma
authors.forename: Karl
authors.initials: K
authors.lastname: Worm
authors.forename: Werner
authors.initials: W
authors.lastname: Paulus
authors.forename: Kathy
authors.initials: K
authors.lastname: Keyvani
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D016657:Cerebral Amyloid Angiopathy / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D004660:Encephalitis / Q000503:physiopathology / Q000517:prevention & control; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018919:Neovascularization, Physiologic / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D010805:Physical Conditioning, Animal / Q000502:physiology*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D000091042:Reelin Protein; D012420:Running / Q000502:physiology; D012697:Serine Endopeptidases / Q000378:metabolism
chemical_list: D016564:Amyloid beta-Protein Precursor; D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717127:RELN protein, human; C000717128:Reln protein, mouse; D012697:Serine Endopeptidases