title: Short-term treadmill exercise increased tau insolubility and neuroinflammation in tauopathy model mice.
abstract: Physical exercise has been identified as a preventive measure for Alzheimer's disease (AD), one of the neuropathological hallmarks of which, neurofibrillary tangles, consist of hyperphosphorylated insoluble tau. Previous studies demonstrated that long-term treadmill exercise reduced tau hyperphosphorylation and insolubility; however, whether short-term treadmill exercise (STE) alters tau modifications currently remains unknown. In the present study, we attempted to characterize the effects of STE on tau solubility and determine its relationship with neuroinflammation using tauopathy model mice (Tg601), which express wild-type human tau. The results obtained showed that 3 weeks of non-shock treadmill exercise in Tg601 and non-transgenic female mice markedly increased insoluble tau. An analysis of phosphorylation patterns indicated that changes in tau solubility were related to an increase in phosphorylation at the tau C-terminal end. The results of immunohistochemical analyses revealed that STE increased the number of Iba-1-positive microglial cells in the hippocampus. Elevations in the levels of the lipid peroxidation markers, 4-hydroxy-trans-2-noneal and malondialdehyde, indicated the presence of oxidative stress. Moreover, higher levels of cytokines, IL-1β and IL-18, and chemokines, CXCL-1 and CXCL-12, supported neuroinflammation.
authors.affiliation: Sportology Center, Juntendo University Graduate of Medicine, Japan; Department of Diagnosis, Prevention and Treatment of Dementia, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Montasir
authors.initials: M
authors.lastname: Elahi
authors.affiliation: Sportology Center, Juntendo University Graduate of Medicine, Japan; Department of Diagnosis, Prevention and Treatment of Dementia, Juntendo University Graduate School of Medicine, Japan; Department of Neurology, Juntendo University Graduate School of Medicine, Japan. Electronic address: motoi@juntendo.ac.jp.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Motoi
authors.affiliation: Department of Diagnosis, Prevention and Treatment of Dementia, Juntendo University Graduate School of Medicine, Japan; Department of Neurology, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Shin-Ei
authors.initials: SE
authors.lastname: Matsumoto
authors.affiliation: Sportology Center, Juntendo University Graduate of Medicine, Japan.
authors.forename: Zafrul
authors.initials: Z
authors.lastname: Hasan
authors.affiliation: Department of Neurology, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Ishiguro
authors.affiliation: Department of Diagnosis, Prevention and Treatment of Dementia, Juntendo University Graduate School of Medicine, Japan; Department of Neurology, Juntendo University Graduate School of Medicine, Japan.
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Hattori
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D015227:Lipid Peroxidation; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress; D010766:Phosphorylation; D010805:Physical Conditioning, Animal; D012995:Solubility; D024801:Tauopathies / Q000378:metabolism* / Q000473:pathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D016875:tau Proteins
keywords: Alzheimer’s disease; Chemokines; Cytokines; Immunohistochemistry; Microglia