Increased recruitment of bone marrow-derived cells into the brain associated with altered brain cytokine profile in senescence-accelerated mice
Increased recruitment of bone marrow-derived cells into the brain associated with altered brain cytokine profile in senescence-accelerated mice
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DOI：
10.1007/s00429-014-0987-2
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发表时间：
2016-04-01
影响因子：
3.1
通讯作者：
Shimada, Atsuyoshi
中科院分区：
文献类型：
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作者：
Hasegawa-Ishii, Sanae;Inaba, Muneo;Shimada, Atsuyoshi
骨髓来源的细胞在非炎症条件下通过脉络丛的附着进入大脑，并分化为分支状的髓样细胞。神经退行性疾病可能与免疫 - 大脑相互作用的改变有关。快速老化小鼠易感10（SAMP10）比C57BL/6（B6）品系更早出现神经退行性变。我们假设在SAMP10小鼠中，从骨髓迁移到大脑的免疫细胞动力学受到干扰。我们使用2月龄（2 mo）和10月龄的SAMP10和B6小鼠作为受体，以绿色荧光蛋白转基因B6小鼠作为供体，通过骨髓内 - 骨髓移植创建了4组辐射嵌合体，并在4个月后进行组织学分析。在[B6 -> 10 mo SAMP10]嵌合体中，比其他嵌合体有更多分支状的骨髓来源细胞分布在更多离散的大脑区域，特别是在间脑。对未经处理的3月龄和12月龄SAMP10和B6小鼠制备的间脑进行多重细胞因子检测显示，12月龄SAMP10小鼠比其他组表现出更高的CXCL1、CCL11、粒细胞集落刺激因子（G - CSF）、CXCL10和白细胞介素 - 6（IL - 6）组织浓度。免疫组织学显示，脉络丛上皮和室管膜产生CXCL1，而脉络丛附着处的星形胶质细胞突起表达CCL11和G - CSF。正中隆起产生CXCL10，下丘脑神经元产生G - CSF，伸长细胞产生CCL11和G - CSF。12月龄SAMP10小鼠的这些大脑细胞因子谱变化可能有助于加速骨髓来源细胞向间脑的动态迁移。对分支状骨髓来源髓样细胞功能的进一步研究将增进我们对脑 - 骨髓相互作用的理解。
Bone marrow-derived cells enter the brain in a non-inflammatory condition through the attachments of choroid plexus and differentiate into ramified myeloid cells. Neurodegenerative conditions may be associated with altered immune-brain interaction. The senescence-accelerated mouse prone 10 (SAMP10) undergoes earlier onset neurodegeneration than C57BL/6 (B6) strain. We hypothesized that the dynamics of immune cells migrating from the bone marrow to the brain is perturbed in SAMP10 mice. We created 4 groups of radiation chimeras by intra-bone marrow-bone marrow transplantation using 2-month-old (2 mo) and 10 mo SAMP10 and B6 mice as recipients with GFP transgenic B6 mice as donors, and analyzed histologically 4 months later. In the [B6 -> 10 mo SAMP10] chimeras, more ramified marrow-derived cells populated a larger number of discrete brain regions than the other chimeras, especially in the diencephalon. Multiplex cytokine assays of the diencephalon prepared from non-treated 3 mo and 12 mo SAMP10 and B6 mice revealed that 12 mo SAMP10 mice exhibited higher tissue concentrations of CXCL1, CCL11, G-CSF, CXCL10 and IL-6 than the other groups. Immunohistologically, choroid plexus epithelium and ependyma produced CXCL1, while astrocytic processes in the attachments of choroid plexus expressed CCL11 and G-CSF. The median eminence produced CXCL10, hypothalamic neurons G-CSF and tanycytes CCL11 and G-CSF. These brain cytokine profile changes in 12 mo SAMP10 mice were likely to contribute to acceleration of the dynamics of marrow-derived cells to the diencephalon. Further studies on the functions of ramified marrow-derived myeloid cells would enhance our understanding of the brain-bone marrow interaction.