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Updated: May 1, 2026
Primary Microglia Isolation from Mixed Glial Cell Cultures of Neonatal Rat Brain Tissue
Published on: August 15, 2012
FGF-2 released from degenerating neurons exerts microglial-induced neuroprotection via FGFR3-ERK signaling pathway
Mariko Noda, Kento Takii, Bijay Parajuli
1Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. tmizuno@riem.nagoya-u.ac.jp.
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.
Insights
Damaged neurons release fibroblast growth factor-2 (FGF-2), which signals microglia to migrate and clear debris. This FGF-2 mediated pathway offers neuroprotection against excitotoxicity via FGFR3-ERK signaling.
Area of Science:
- Neuroscience
- Cell Biology
- Neuroimmunology
Background:
- Activated microglia accumulate in neurodegenerative diseases, exhibiting dual protective and toxic roles.
- Microglial migration to lesions is mediated by chemokines, with fibroblast growth factor-2 (FGF-2) known as a migratory factor in zebrafish.
- The role of FGF-2 in mammalian central nervous system (CNS) microglial function remains largely unexplored.
Purpose of the Study:
- To investigate the influence of FGF-2 on microglial function in the mammalian CNS.
- To elucidate the signaling pathways involved in FGF-2-mediated microglial responses.
- To determine the neuroprotective potential of FGF-2 in neuronal injury models.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) for FGF-2 release.
- Immunocytochemistry for receptor expression, neuronal survival, and microglial phagocytosis.
- Fluorescence-activated cell sorting (FACS) for microglial migration assessment.
- Western blotting and promoter assays for downstream signaling pathway analysis.
Main Results:
- Neurons release FGF-2 upon damage from glutamate or amyloid-β.
- FGF-2 promotes microglial migration and phagocytosis of neuronal debris.
- FGF-2 confers neuroprotection against glutamate toxicity via the FGFR3-ERK signaling pathway.
- Wnt signaling directly regulates FGF-2-induced downstream signaling in microglia.
Conclusions:
- FGF-2 released by degenerating neurons acts as a 'help-me' signal to microglia.
- This signaling induces microglial migration and phagocytosis of cellular debris.
- FGF-2 plays a crucial role in neuroprotection and debris clearance in the CNS.
