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SAMP8 mice as a neuropathological model of accelerated brain aging and dementia: Toshio Takeda's legacy and future directions
Author(s) -
Akiguchi Ichiro,
Pallàs Mercè,
Budka Herbert,
Akiyama Haruhiko,
Ueno Masaki,
Han Jingxian,
Yagi Hideo,
Nishikawa Tomohumi,
Chiba Yoichi,
Sugiyama Hiroshi,
Takahashi Ryoya,
Unno Keiko,
Higuchi Keiichi,
Hosokawa Masanori
Publication year - 2017
Publication title -
neuropathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.701
H-Index - 61
eISSN - 1440-1789
pISSN - 0919-6544
DOI - 10.1111/neup.12373
Subject(s) - astrogliosis , hippocampus , senescence , neuroscience , hippocampal formation , locus coeruleus , gliosis , atrophy , medicine , pathology , biology , central nervous system
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.