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

Jian Luo, Fiona Elwood, Markus Britschgi, Saul Villeda, Hui Zhang, Zhaoqing Ding, Liyin Zhu, Haitham Alabsi, Ruth Getachew, Ramya Narasimhan, Rafael Wabl, Nina Fainberg, Michelle L James, Gordon Wong, Jane Relton, Sanjiv S Gambhir, Jeffrey W Pollard, Tony Wyss-Coray

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)157-72
Number of pages16
JournalJournal of Experimental Medicine
Volume210
Issue number1
DOIs
Publication statusPublished - 14 Jan 2013

Keywords

  • Amyloid beta-Protein Precursor
  • Animals
  • Base Sequence
  • Cell Survival
  • Cognition
  • Cyclic AMP Response Element-Binding Protein
  • Disease Models, Animal
  • Humans
  • Interleukins
  • Kainic Acid
  • Macrophage Colony-Stimulating Factor
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Molecular Sequence Data
  • Neurodegenerative Diseases
  • Neurons
  • Neuroprotective Agents
  • Phosphorylation
  • Prosencephalon
  • Receptor, Macrophage Colony-Stimulating Factor
  • Recombinant Proteins
  • Signal Transduction

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