title: FGF-2 released from degenerating neurons exerts microglial-induced neuroprotection via FGFR3-ERK signaling pathway.
abstract: BACKGROUND
  The accumulation of activated microglia is a hallmark of various neurodegenerative diseases. Microglia may have both protective and toxic effects on neurons through the production of various soluble factors, such as chemokines. Indeed, various chemokines mediate the rapid and accurate migration of microglia to lesions. In the zebra fish, another well-known cellular migrating factor is fibroblast growth factor-2 (FGF-2). Although FGF-2 does exist in the mammalian central nervous system (CNS), it is unclear whether FGF-2 influences microglial function.
  
  
  METHODS
  The extent of FGF-2 release was determined by ELISA, and the expression of its receptors was examined by immunocytochemistry. The effect of several drug treatments on a neuron and microglia co-culture system was estimated by immunocytochemistry, and the neuronal survival rate was quantified. Microglial phagocytosis was evaluated by immunocytochemistry and quantification, and microglial migration was estimated by fluorescence-activated cell sorting (FACS). Molecular biological analyses, such as Western blotting and promoter assay, were performed to clarify the FGF-2 downstream signaling pathway in microglia.
  
  
  RESULTS
  Fibroblast growth factor-2 is secreted by neurons when damaged by glutamate or oligomeric amyloid β 1-42. FGF-2 enhances microglial migration and phagocytosis of neuronal debris, and is neuroprotective against glutamate toxicity through FGFR3-extracellular signal-regulated kinase (ERK) signaling pathway, which is directly controlled by Wnt signaling in microglia.
  
  
  CONCLUSIONS
  FGF-2 secreted from degenerating neurons may act as a 'help-me' signal toward microglia by inducing migration and phagocytosis of unwanted debris.
authors.forename: Mariko
authors.initials: M
authors.lastname: Noda
authors.forename: Kento
authors.initials: K
authors.lastname: Takii
authors.forename: Bijay
authors.initials: B
authors.lastname: Parajuli
authors.forename: Jun
authors.initials: J
authors.lastname: Kawanokuchi
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Sonobe
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takeuchi
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. tmizuno@riem.nagoya-u.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizuno
authors.forename: Akio
authors.initials: A
authors.lastname: Suzumura
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D054405:Chemokine CCL3 / Q000378:metabolism; D004622:Embryo, Mammalian; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D009410:Nerve Degeneration / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000378:metabolism*
chemical_list: D054405:Chemokine CCL3; D016222:Fibroblast Growth Factor 2; D009569:Nitric Oxide; D018698:Glutamic Acid; D051498:Receptor, Fibroblast Growth Factor, Type 3
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