Effects of FGF2/FGFR1 Pathway on Expression of A1 Astrocytes After Infrasound Exposure.

Two types of reactive astrocytes, A1 and A2 astrocytes, are induced following neuroinflammation and ischemia. In this study, we evaluated the effects of the fibroblast growth factor (FGF)2/FGF receptor (FGFR)1 pathway on A1 and A2 astrocytes in the rat hippocampus using double-labeling immunofluorescence following infrasound exposure. A1 astrocytes were induced in the CA1 region of the hippocampus after exposure to infrasound for 3 days. The number of microglial cells was also increased, and we investigated if these might be responsible for the reactivity of A1 astrocytes. Accordingly, expression levels of C3 and Iba-1, as markers of A1 astrocytes and microglial cells, respectively, were both up-regulated in rat hippocampus following infrasound exposure, as demonstrated by western blot. We also explored the effect of the FGF2/FGFR1 pathway on A1 astrocyte reactivity by pretreating rats with FGF2 or the specific FGFR1 antagonist, PD173074. A1 astrocytes were gradually down-regulated by activation of the FGF2/FGFR1 pathway and were up-regulated by inhibition of the FGF2/FGFR1 pathway after infrasound damage. These results further our understanding of the role of reactive astrocytes in infrasound-induced central nervous system injury and will thus facilitate the development of new treatments for these injuries.

Inhibitive Effects of FGF2/FGFR1 Pathway on Astrocyte-Mediated Inflammation in vivo and in vitro After Infrasound Exposure.

Infrasound, a kind of ambient noise, can cause severe disorders to various human organs, specially to central nervous system (CNS). Our previous studies have shown that infrasound-induced CNS injury was closely related with astrocytes activation and astrocytes-mediated neuroinflammation, but the underlying molecular mechanisms are still largely unclear. FGF2/FGFR1 (Fibroblast growth factor 2/Fibroblast growth factor receptor 1) pathway was reported to play an important role in anti-inflammation in CNS disorders. To further study the possible roles of FGF2/FGFR1 pathway in infrasound-induced CNS injury, here we exposed Sprague-Dawley rats or cultured astrocytes to 16 Hz, 150 dB infrasound, and explored the effects of FGF2 on infrasound-induced astrocytes activation and neuroinflammation. Western blotting, immunofluorescence and liquid chip method were used in this experiment. Our results showed that after 3- or 7-day exposure (2 h/day) of rats as well as 2 h exposure of cultured astrocytes to 16 Hz, 150 dB infrasound, astrocyte-expressed FGFR1 was downregulated in vivo and in vitro. FGF2 pretreatment not only inhibited infrasound-induced astrocyte activation in rat hippocampal CA1 region, but also reduced the levels of pro-inflammatory cytokines, such as TNF-α, IL-1ß, IL-18, IL-6, and IFN-γ in vitro and in vivo. However, FGF2 significantly upregulated the expression of FGFR1. Furthermore, we showed that FGF2 could attenuate IκBα phosphorylation, NF-κB p65 translocation, pro-inflammatory cytokines levels, and neuronal loss in the CA1 region induced by infrasound. On the contrary, PD173074, a special antagonist of FGFR1, could reverse the effects above in vitro and in vivo. Taken together, our findings showed that FGF2/FGFR1 pathway may exert inhibitive effects on astrocyte-mediated neuroinflammation in vitro and in vivo after infrasound exposure.