| Project/Area Number |
14370436
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cerebral neurosurgery
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| Research Institution | Kagawa University |
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Principal Investigator |
MATSIUNOTO Yoshihito Kagawa University, Department of neurological Surgery, Assistant Professor, 医学部附属病院, 助手 (80311827)
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| Co-Investigator(Kenkyū-buntansha) |
NAGAO Seigo Kagawa University, Department of neurological Surgery, Professor, 医学部附属病院, 教授 (60100947)
KAWAI Nobuyuki Kagawa University, Department of neurological Surgery, Associate Professor, 医学部附属病院, 講師 (40294756)
國塩 勝三 香川医科大学, 医学部, 助教授 (50273983)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥4,200,000 (Direct Cost: ¥4,200,000)
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| Keywords | ES cell / cholinergic neuron / neural stem cell / Alzheimer's disease / transplantation / medial septum / epilepsy / GABA / コリン作動性神経細胞 / アルツハイマー病 / 移植治療 / コリン作動性細胞 / ChAT / 海馬 |
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| Research Abstract |
Objective. The goal of this study was to elucidate the effect of neurospheres (NS) on dementia and epilepsy in the mouse models.
Methods. Dementia model ; Mouse embryonic stem cell (ES) derived neurospheres were transplanted into the frontal association cortex and barrel field of S1 cortex of C57BL/6 mice 4 weeks after including a lesion of NBM by ibotenic acid, while other healthy mice that received ES cells served as control. Behavioral tests by water maze or 8-arm radial maze were conducted 8 weeks after transplantation, and double staining of choline acetyltransferase (ChAT), and green fluorescent protein (GFP) 12 weeks after transplantation. Epilepsy model ; A total of 14 kindled mice were used in this experiment. The response of kindling consisted of progressively more clinical seizures as described by Racine. Following stage 5 kindling, the mice were divided into two groups. In group 1, the NS cells derived from the ES cells were transplanted into the dorsal hippocampal area (n=7
… More
). Group 2 received microinjections of cell-free medium only (n=7). After transplantation, the severity of seizures was classified by the score of Racine again. All the mice were perfused and fixed for immunohistological analysis after finishing the kindling experiment. Moreover, the transplants were stained for green fluorescent protein (GFP) because GFP gene was inserted in the ES cells so as to distinguish the transplants from the host cells.
Results : Dementia model ; We found that the neurospheres transplanted into the mouse cortex survived and produced many ChAT-positive neurons in and around the grafts. The working memory error decreased significantly in the mice grafted with neurospheres. In contrast, the ES cells developed into teratomas in all of the control mice and expressed no neurons, and the working memory deteriorated remarkably. Epilepsy model ; In group 1, one mouse was classified as stage 0, five mice were stage 3, and one mouse was stage 4 recovering from stage 5 at six weeks after transplantation. No such alteration was seen in group 2. The transplants were stained with neuronal (Hu) and GABAergic (GAD 67) markers, indicating that these cells differentiated into GABAergic neurons. Less
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