Investigation of the mechanisms of the degeneration and death of neuronal cells using a culture model.
| Project/Area Number |
14570186
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Institute for Developmental Research, Aichi Human Service Center |
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Principal Investigator |
HOSOKAWA Masanori Inst.for Developmental Research, Aichi Human Service Cent., Department of Pathology, Department Head, 病理学部, 部長 (00127135)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Hyper oxidative Stress / Cell Culture / Reactive Oxygen Species / Mitochondria / Anti Oxidants Enzymes / Model Mice / Neuronal Cells / Fibroblast-like Cells |
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| Research Abstract |
The SAM strains are consisting of a series of SAMP and SAMR strains. When compared with the SAMR strains, the SAMP strains of mice show a more accelerated senescence process, shorter lifespan, and an earlier onset and more rapid progress of age-associated pathological phenotypes. The higher oxidative status and mitochondrial dysfunction were observed in various organs in SAMP strains of mice.
The senescence acceleration is also observed during senescence in cultures of isolated dermal fibroblast-like cells from SAMP11 mice, and was associated with a higher oxidative status. The quantity of reactive oxygen species (ROS) was greater than that in the SAMR1 cells, a control cells, after the 7th day in culture. Enzymatic activity and mRNA quantity of the antioxidant enzymes could not account for the difference in ROS production. Mitochondria with degenerated ultrastructures and low membrane potential were increased in the SAMP11 cells with time. We observed these dysfunctional mitochondria having an abnormal appearance in various tissues from old SAMP mice.
The SAMP10 mice developed diffuse atrophy in the cerebral neocortex, especially frontal cortex, with advancing age. The Number of neurons in the cortex decreased with aging. TUNEL assays revealed an age-related increase in the number of TUNEL-positive cells with aging and these cells were interpreted to undergo DNA damage through a mechanism other than apoptosis. There were also intra neuronal inclusions in aged SAMP10 mice.
We have developed a culture system of neuronal cells and astroglia from these SAMP and SAMR strains including SAMP10 mice. Purity of the cells in each culture was over 99%. Now we are investigating the molecular basis of the neuronal degeneration under intrinsic hyperoxidative status in SAMP10 mice.
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Report
(3 results)
Research Products
(20 results)
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[Publications] Y.Chiba, Y.Yamashita, K.Hirayoshi, M.Ueno, H.Fujisawa, I.Akiguchi, T.Matsushita, K.Kogishi, M.Satoh, A.Shimada, M.Hosokawa: "Mitochondrial alterations and a higher oxidative status in cultured fibroblast-like cells from senescence-accelerated mice."ibid. 255-258
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