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Endogenous FGF-2 is important for cholinergic sprouting in the denervated hippocampus
A M Fagan1, S T Suhr, C A Lucidi-Phillipi
1Laboratory of Genetics, The Salk Institute, La Jolla, California 92037, USA.
Summary
Fibroblast growth factor-2 (FGF-2) promotes cholinergic axonal sprouting in the injured adult brain. This occurs via direct action on basal forebrain cholinergic neurons, suggesting a novel therapeutic target for brain injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Cholinergic sprouting in the hippocampus is crucial for cognitive function after injury.
- Nerve growth factor (NGF) was previously thought to mediate this response, but evidence was lacking.
Purpose of the Study:
- To investigate the molecular mechanisms underlying cholinergic sprouting in the hippocampus following entorhinal cortex removal.
- To determine the role of fibroblast growth factor-2 (FGF-2) in this process.
Main Methods:
- Evaluated trophic factor gene expression in the denervated hippocampus.
- Measured FGF-2 mRNA and protein levels post-lesion.
- Used neutralizing antibodies against FGF-2 to assess its functional significance.
- Localized FGF-2 receptors (FGFR1) on basal forebrain cholinergic neurons.
Main Results:
- FGF-2 mRNA levels significantly increased within 16 hours post-lesion, unlike NGF.
- FGF-2 immunoreactivity was observed in hypertrophic astrocytes in the denervated area.
- Infusion of FGF-2 antibodies markedly reduced cholinergic sprouting.
- FGFR1 was localized on basal forebrain cholinergic neurons, indicating a direct signaling pathway.
Conclusions:
- Endogenous FGF-2 actively promotes cholinergic axonal sprouting in the injured adult brain.
- FGF-2 likely acts directly on basal forebrain cholinergic neurons to mediate this sprouting response.
- These findings identify FGF-2 as a key mediator of neural repair and a potential therapeutic target.