title: SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions.
abstract: Senescence accelerated mice P8 (SAMP8) show significant age-related deteriorations in memory and learning ability in accordance with early onset and rapid advancement of senescence. Brains of SAMP8 mice reveal an age-associated increase of PAS-positive granular structures in the hippocampal formation and astrogliosis in the brain stem and hippocampus. A spongy degeneration in the brain stem appears at 1 month of age and reaches a maximum at 4-8 months. In addition, clusters of activated microglia also appear around the vacuoles in the brain stem. β/A4(Aβ) protein-like immunoreactive granular structures are observed in various regions and increase in number markedly with age. Other age-associated histological changes include cortical atrophy, neuronal cell loss in locus coeruleus and lateral tegmental nuclei, intraneuronal accumulation of lipopigments in Purkinje cells and eosinophilic inclusion bodies in thalamic neurons. A blood-brain barrier dysfunction and astrogliosis are also prominent with advancing age in the hippocampus. These changes are generally similar to the pathomorphology of aging human brains and characterized by their association with some specific glioneuronal reactions. As for the hallmarks of Alzheimer brains, tau morphology has not yet been confirmed regardless of the age-related increase in phosphorylated tau in SAMP8 mice brains, but early age-related Aβ deposition in the hippocampus has recently been published. SAMP8 mice are, therefore, not only a senescence-accelerated model but also a promising model for Alzheimer's disease and other cognitive disorders.
authors.affiliation: Center of Neurological and Cerebrovascular Diseases, Koseikai Takeda Hospital, Kyoto, Japan.|Department of Health Science, Kyoto Koka Women's University, Kyoto, Japan.
authors.forename: Ichiro
authors.identifier: http://orcid.org/0000-0003-2091-2720
authors.initials: I
authors.lastname: Akiguchi
authors.affiliation: Pharmacology Section and Institute of Neuroscience, University of Barcelona, Barcelona, Spain.
authors.forename: Mercè
authors.initials: M
authors.lastname: Pallàs
authors.affiliation: Institute of Neuropathology, University Hospital Zurich, Zurich, Switzerland.
authors.forename: Herbert
authors.initials: H
authors.lastname: Budka
authors.affiliation: Department of Clinical Research, Yokohama Brain and Spine Center, Yokohama, Japan.
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Akiyama
authors.affiliation: Department of Pathology and Host Defence, Faculty of Medicine, Kagawa University, Takamatsu, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Ueno
authors.affiliation: The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
authors.forename: Jingxian
authors.initials: J
authors.lastname: Han
authors.affiliation: Center of Neurological and Cerebrovascular Diseases, Koseikai Takeda Hospital, Kyoto, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagi
authors.affiliation: Department of Health Science, Kyoto Koka Women's University, Kyoto, Japan.
authors.forename: Tomohumi
authors.initials: T
authors.lastname: Nishikawa
authors.affiliation: Department of Pathology and Host Defence, Faculty of Medicine, Kagawa University, Takamatsu, Japan.
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Chiba
authors.affiliation: National Hospital Organization Utano Hospital, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sugiyama
authors.affiliation: Department of Biochemistry, Faculty of Pharmaceutical Sciences, Toho University, Chiba, Japan.
authors.forename: Ryoya
authors.initials: R
authors.lastname: Takahashi
authors.affiliation: School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Unno
authors.affiliation: Department of Aging Biology, Institute of Pathogenesis and Disease Prevention, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Higuchi
authors.affiliation: Institute for Developmental Research, Aichi Human Service Center, Nagoya, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Hosokawa
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001921:Brain / Q000473:pathology*; D003704:Dementia / Q000473:pathology*; D004195:Disease Models, Animal; D051379:Mice; D008817:Mice, Mutant Strains
keywords: Alzheimer's disease; SAMP8; brainstem; hippocampus; senescence-accelerated model