Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation

Area of Science:

• Neuroscience
• Toxicology
• Molecular Biology

Background:

• Infrasound exposure causes central nervous system (CNS) injury, linked to astrocyte activation and neuroinflammation.
• The molecular mechanisms of infrasound-induced CNS injury remain unclear.
• The Fibroblast growth factor 2 (FGF2)/Fibroblast growth factor receptor 1 (FGFR1) pathway is implicated in anti-inflammation within the CNS.

Purpose of the Study:

• To investigate the role of the FGF2/FGFR1 pathway in mitigating infrasound-induced CNS injury.
• To explore the effects of FGF2 on infrasound-induced astrocyte activation and neuroinflammation.
• To elucidate the molecular mechanisms underlying FGF2's protective effects.

Main Methods:

• Exposure of Sprague-Dawley rats and cultured astrocytes to 16 Hz, 150 dB infrasound.
• Utilized Western blotting, immunofluorescence, and liquid chip assays.
• Administered FGF2 pretreatment and FGFR1 antagonist PD173074.

Main Results:

• Infrasound downregulated astrocyte-expressed FGFR1 in vivo and in vitro.
• FGF2 pretreatment inhibited infrasound-induced astrocyte activation and reduced pro-inflammatory cytokines (TNF-α, IL-1β, IL-18, IL-6, IFN-γ).
• FGF2 upregulated FGFR1, attenuated NF-κB signaling, and protected against neuronal loss; PD173074 reversed these effects.

Conclusions:

• The FGF2/FGFR1 pathway plays a protective role against infrasound-induced CNS injury.
• FGF2/FGFR1 activation inhibits astrocyte-mediated neuroinflammation by suppressing NF-κB signaling.
• Targeting the FGF2/FGFR1 pathway may offer a therapeutic strategy for infrasound-related CNS disorders.