Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival.
Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival.
复制标题
DOI：
10.1084/jem.20120412
复制
发表时间：
2013-01-14
期刊：
影响因子：
--
通讯作者：
Wyss-Coray T
中科院分区：
文献类型：
--
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
集落刺激因子1和IL-34通过促进CREB信号传导来预防和部分逆转小鼠神经退行性变。集落刺激因子1 （CSF1）和白细胞介素-34 （IL-34）是CSF1受体（CSF1R）的功能性配体，因此是单核细胞/巨噬细胞谱系的关键调节因子。我们发现，在阿尔茨海默病转基因小鼠模型中，系统给药人重组CSF1可改善记忆缺陷。CSF1和IL-34在损伤前或损伤后6小时内给药，可显著减少兴奋毒素诱导的神经细胞损失和神经胶质瘤。这些影响伴随着cAMP响应元件结合蛋白（CREB）信号在神经元而不是小胶质细胞中的维持。通过谱系示踪实验，我们发现在生理条件下，海马和皮层中有少量神经元表达CSF1R， kainic酸诱导的兴奋性损伤导致神经元受体表达显著增加。小鼠前脑神经元CSF1R的选择性缺失加重了兴奋毒素诱导的死亡和神经变性。我们得出结论，CSF1和IL-34在脑损伤和神经退行性变中提供强大的神经保护和生存信号，涉及神经元上CSF1R的表达。
Colony-stimulating factor 1 and IL-34 protect against and partially reverse neurodegeneration in mice in part via promoting CREB signaling. Colony-stimulating factor 1 (CSF1) and interleukin-34 (IL-34) are functional ligands of the CSF1 receptor (CSF1R) and thus are key regulators of the monocyte/macrophage lineage. We discovered that systemic administration of human recombinant CSF1 ameliorates memory deficits in a transgenic mouse model of Alzheimer’s disease. CSF1 and IL-34 strongly reduced excitotoxin-induced neuronal cell loss and gliosis in wild-type mice when administered systemically before or up to 6 h after injury. These effects were accompanied by maintenance of cAMP responsive element–binding protein (CREB) signaling in neurons rather than in microglia. Using lineage-tracing experiments, we discovered that a small number of neurons in the hippocampus and cortex express CSF1R under physiological conditions and that kainic acid–induced excitotoxic injury results in a profound increase in neuronal receptor expression. Selective deletion of CSF1R in forebrain neurons in mice exacerbated excitotoxin-induced death and neurodegeneration. We conclude that CSF1 and IL-34 provide powerful neuroprotective and survival signals in brain injury and neurodegeneration involving CSF1R expression on neurons.
登录
查看更多内容
影响因子：
5.3
作者：
Adlard, PA;Perreau, VM;Cotman, CW
通讯作者：
Cotman, CW
影响因子：
5.4
作者：
Casals-Casas, Cristina;Alvarez, Eva;Celada, Antonio
通讯作者：
Celada, Antonio
影响因子：
6.2
作者：
Imai, Y;Kohsaka, S
通讯作者：
Kohsaka, S
影响因子：
14.5
作者：
Boissonneault, Vincent;Filali, Mohammed;Rivest, Serge
通讯作者：
Rivest, Serge
影响因子：
7
作者：
Britschgi, Markus;Rufibach, Kaspar;Wyss-Coray, Tony
通讯作者：
Wyss-Coray, Tony