Project/Area Number |
20300129
|
Research Category |
Grant-in-Aid for Scientific Research (B)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Neurochemistry/Neuropharmacology
|
Research Institution | Kumamoto University |
Principal Investigator |
KAGAWA Tetsushi Kumamoto University, 難治疾患研究所, 准教授 (50270484)
|
Co-Investigator(Renkei-kenkyūsha) |
KASHIWAGI Taichi 東京医科歯科大学, 難治疾患研究所, 特任助教 (10398232)
|
Project Period (FY) |
2008 – 2010
|
Project Status |
Completed (Fiscal Year 2010)
|
Budget Amount *help |
¥19,630,000 (Direct Cost: ¥15,100,000、Indirect Cost: ¥4,530,000)
Fiscal Year 2010: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2009: ¥6,630,000 (Direct Cost: ¥5,100,000、Indirect Cost: ¥1,530,000)
Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
|
Keywords | グリア細胞 / シナプス形成 / 神経回路網 / 発生 / アストロサイト |
Research Abstract |
In the vertebrate central nervous system (CNS), astrocytes perform multiple functions to support neural activities: including provision of neutrients to neurons, recycling of neurotransmitters and formation of blood brain barrier. In addition to their classical roles, recent studies have demonstrated that glial cells are widely involved in the regulation of synaptogenesis and synaptic activities. However, it has been poorly understood whether astrocytes can be classified into widely divergent cell lineages with their specific functions. If so, the mechanisms and timing of astrocyte sub-lineage commitments are interesting subjects. Alternatively, astrocytes may be a homogeneous cell population and adopt to change their functions according to their local environment. To challenge this question, we established a GFAP/Cre-reporter mouse line that carries the "loxP-nlacZ-loxP-GAP43GFP" cassette in glial fibrillary acidic protein (GFAP) gene locus. In this mouse CNS, only a sub-lineage of astrocytes, whose ancestral progenitor cells express cre recombinase, express GAP43GFP. As a first step, the GFAP/loxP-reporter mice were crossbred with Emx1-Cre KI Δneo mice (provided by Drs. Iwasato and Itohara) to label Emx1-positive pallial progenitors-derived astorocytes as GFP+ cells. Most astrocytes in cortical plate were βGal-/GFP+, while a subpopulation of midline glia that guided corpus callosum formation were βGal+/GFP-, suggesting that functionally different cortical astrocytes and midline glia were generated from different origins. To further investigate unique functions, if any, for the cortical and hippocampal GFAP+ cells, they were isolated using cell sorter and subjected for gene expression microarray analysis. Hippocampal GFAP+ cells expressed several genes characteristic of neural progenitor cells and immature neurons.
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