Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival

Abstract

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.

DOI: 10.1084/jem.20120412

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@inproceedings{Luo2013ColonystimulatingF1, title={Colony-stimulating factor 1 receptor (CSF1R) signaling in injured neurons facilitates protection and survival}, author={Jian Luo and Fiona Elwood and Markus Britschgi and Saul Villeda and Hui Zhang and Zhaoqing Ding and Liyin Zhu and Haitham Alabsi and Ruth Getachew and Ramya Narasimhan and Rafael Wabl and Nina Fainberg and Michelle L. James and Gordon Wong and Jane Relton and Sanjiv S. Gambhir and Jeffrey W. Pollard and Tony Wyss-Coray}, booktitle={The Journal of experimental medicine}, year={2013} }