| 現在までの達成度 (区分) |
現在までの達成度 (区分)
1: 当初の計画以上に進展している
理由
Inflammatory cytokines, IL-6 and TNF-α are increased in BTBR brains from early embryonic brain, E12, to early postnatal day 5. As the brain matures, increased inflammatory cytokines are limited to cerebellum. The spine density in the purkinje cell is found to be increased in BTBR. It is proposed that the inflammatory environment in early developmental stages will lead to hyper-connectivity in local brain regions. Primary culture of microglia, astrocyte and neuron are established to clarify which cell type is responsible for the inflammation in brain. The result suggests only microglia from BTBR shows similar change in the cytokine profiles as observed in the brain. Furthermore, PU.1, the transcription factor involving in microglia differentiation/activation, is increased in BTBR microglia. This suggests the abnormal microglia development. In addition to inflammation in brain, we also find that cytokine expression is changed in BTBR colon. Microglia and peripheral immune cells are differentiated from hematopoietic stem cells (HSC) in yolk sac and aorta-gonad mesonephros (AGM), respectively, during embryonic stage. After birth, HSC are mainly located in bone marrow. To investigate whether pathologic HSC causes impaired development of immune cells and leads to aberrant cytokine expression, B6 were exposed to sublethal dose of total body irradiation and received bone marrow from BTBR mice. The preliminary result shows the recipient B6 can partially recapitulate the inflammatory phenotypes observed in BTBR.
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