Microglial reduction of colony stimulating factor-1 receptor expression is sufficient to confer adult onset leukodystrophy.
Microglial reduction of colony stimulating factor-1 receptor expression is sufficient to confer adult onset leukodystrophy.
复制标题
小胶质细胞减少集落刺激因子-1受体的表达足以导致成人发病的脑白质营养不良。
作者：
Biundo F;Chitu V;Shlager GGL;Park ES;Gulinello ME;Saha K;Ketchum HC;Fernandes C;Gökhan Ş;Mehler MF;Stanley ER
伴有轴突球体和色素胶质细胞的成人型白质脑病（ALSP）是一种显性遗传性CSF 1 R失活突变引起的痴呆。Csf 1 r +/−小鼠模拟ALSP症状和病理。Csf 1 r主要在小胶质细胞中表达，但也在皮质V层神经元中表达，这些神经元在Csf 1 r +/−小鼠中随着年龄的增长而逐渐丢失。因此，我们研究了小胶质细胞或神经元Csf 1 r缺失是否会导致Csf 1 r +/−小鼠的神经退行性变。先前在Csf 1 r +/− ALSP小鼠中描述的导致疾病的行为缺陷、病理和Csf 2表达升高通过小胶质细胞缺失（MCsf 1 rht小鼠）重现，但不能通过神经缺失重现。此外，在Csf 1 r +/−小鼠中观察到胼胝体星形胶质细胞、少突胶质细胞和小胶质细胞表达Csf 2增加，在MCsf 1 rht小鼠中，这三种细胞类型的密度在显示激活的小胶质细胞（疾病病理学的早期部位）的室上斑中增加。这些数据证实了ALSP是一种原发性小胶质细胞病，并为未来的治疗和实验方法提供了信息。
Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a dementia resulting from dominantly inherited CSF1R inactivating mutations. The Csf1r+/− mouse mimics ALSP symptoms and pathology. Csf1r is mainly expressed in microglia, but also in cortical layer V neurons that are gradually lost in Csf1r+/− mice with age. We therefore examined whether microglial or neuronal Csf1r loss caused neurodegeneration in Csf1r+/− mice. The behavioral deficits, pathologies and elevation of Csf2 expression contributing to disease, previously described in the Csf1r+/− ALSP mouse, were reproduced by microglial deletion (MCsf1rhet mice), but not by neural deletion. Furthermore, increased Csf2 expression by callosal astrocytes, oligodendrocytes, and microglia was observed in Csf1r+/− mice and, in MCsf1rhet mice, the densities of these three cell types were increased in supraventricular patches displaying activated microglia, an early site of disease pathology. These data confirm that ALSP is a primary microgliopathy and inform future therapeutic and experimental approaches.
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影响因子：
14.5
作者：
Gelfand, Jeffrey M.;Greenfield, Ariele L.;Mannis, Gabriel N.
通讯作者：
Mannis, Gabriel N.
影响因子：
6.4
作者：
Dziedzic, Tomasz;Metz, Imke;Brueck, Wolfgang
通讯作者：
Brueck, Wolfgang
DOI：
10.1084/jem.20120412
发表时间：
2013-01-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Luo J;Elwood F;Britschgi M;Villeda S;Zhang H;Ding Z;Zhu L;Alabsi H;Getachew R;Narasimhan R;Wabl R;Fainberg N;James ML;Wong G;Relton J;Gambhir SS;Pollard JW;Wyss-Coray T
通讯作者：
Wyss-Coray T
影响因子：
20.3
作者：
Dai, XM;Ryan, GR;Stanley, ER
通讯作者：
Stanley, ER
影响因子：
6.4
作者：
Hoffmann, Sarah;Murrell, Jill;Stenzel, Werner
通讯作者：
Stenzel, Werner