1992 Fiscal Year Final Research Report Summary
Development of murine models for aging brain, Senescence-Accelerated Mouse (SAM)
| Project/Area Number |
02507002
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| Research Category |
Grant-in-Aid for Developmental Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
Experimental pathology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
TAKEDA Toshio Chest Dis. Res. Inst., Kyoto Univ., Dept. of Senescence Biology, Professor, 胸部疾患研究所, 教授 (00027088)
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| Co-Investigator(Kenkyū-buntansha) |
HIGUCHI Keiichi Chest Dis. Res. Inst.,Kyoto Univ., Dept. of Senescence Biology, Lecturer, 胸部疾患研究所, 講師 (20173156)
HOSOKAWA Masanori Chest Dis. Red. Inst.,Kyoto Univ., Dept. of Senesce. Biology, Assoc. Prof., 胸部疾患研究所, 助教授 (00127135)
AKIGCHI Ichiro Faculty of Med.,Kyoto Univ.,Dept. of Neurology, Assoc. Professor, 医学部, 助教授 (30115779)
MIYAMOTO Masaomi Takeda Chem. Ing.,LTD.,Dept. I, Pharmaceutical Res.Labs.I., Chief, 第1創薬研究所, 主任研究員
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| Project Period (FY) |
1990 – 1992
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| Keywords | Senescence-Accelerated Mouse (SAM) / Animal model / Senescence / Deficits in learning & memory / Brain atrophy / 脳萎縮 |
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| Research Abstract |
1. Neuroaxonal dystrophic changes were observed in the nuclei fasciculi dorsalis of medulla oblongata in SAM-P/8 mice. The changes appeared earlier and progressed more rapidly in SAM-P/8 than did in SAM-R/U. beta/A4 protein-like immunoreactivity was observed in the form of granular structures(beta-LIGS) in various regions,including the medial septum, cerebral cortex, hippocampu and so on. beta-LIGS increased in number with aging, predominantly in SAM-P/8 with deficits in learning and memory.
2. The vacuolization in SAM-P/8 was marked in magnocellular reticula formation (MGRF). The severity of deficits in learning and memory closely correlated with the total area and number of vacuoles in MGRF of brain stem. Furthermore, MGRF lesioned SAM-R/1 mice showed a severe deterioration in passive avoidance tasks and an impairment in the acquisition stage of active avoidance performance. These results strongly suggest that a pathogenic role of the spongiform degeneration in brain stem in deficits in learning and memory in SAM-P/8.
3. An inbred SAM-P/10 strain has been established as a model of agerelated brain atrophy. Morphometrical studies showed that frontal cortex including prefrontal cortex, other neocortical regions, posterior piriform cortex, entorhinal cortex anterior olfactory nucleus, amygdala, and caudate putamen were atrophy-prone regions Shrinkage of the neuronal somata and loss of large neurons with age are unique for SAM-P/10, both of which bring about age-relate atrophy in cerebral cortex in SAM-P/10.
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