Fibroblast Growth Factor 9 Stimulates Neuronal Length Through NF-kB Signaling in Striatal Cell Huntington’s Disease Models

Abstract

Proper development of neuronal cells is important for brain functions, and impairment of neuronal development may lead to neuronal disorders, implying that improvement in neuronal development may be a therapeutic direction for these diseases. Huntington’s disease (HD) is a neurodegenerative disease characterized by impairment of neuronal structures, ultimately leading to neuronal death and dysfunctions of the central nervous system. Based on previous studies, fibroblast growth factor 9 (FGF9) may provide neuroprotective functions in HD, and FGFs may enhance neuronal development and neurite outgrowth. However, whether FGF9 can provide neuronal protective functions through improvement of neuronal morphology in HD is still unclear. Here, we study the effects of FGF9 on neuronal length in HD and attempt to understand the related working mechanisms. Taking advantage of striatal cell lines from HD knock-in mice, we found that FGF9 increases total neuronal length and upregulates several structural and synaptic proteins under HD conditions. In addition, activation of nuclear factor kappa B (NF-kB) signaling by FGF9 was observed to be significant in HD cells, and blockage of NF-kB leads to suppression of these structural and synaptic proteins induced by FGF9, suggesting the involvement of NF-kB signaling in these effects of FGF9. Taken these results together, FGF9 may enhance total neuronal length through upregulation of NF-kB signaling, and this mechanism could serve as an important mechanism for neuroprotective functions of FGF9 in HD.

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Data Availability

The datasets and materials used and/or analyzed during the current study are available from the corresponding author upon reasonable request.

Abbreviations

HD:

Huntington’s disease

FGF9:

Fibroblast growth factor 9

NF-kB:

Nuclear factor kappa B

PD:

Parkinson’s disease

Q7:

STHdhQ7/Q7

Q111:

STHdhQ111/Q111

MAP 2:

Microtubule-associated protein

GAP-43:

Growth association protein 43

FGFR:

FGF receptor

Shh:

Sonic Hedge Hog

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Authors and Contributors

IOY, HMC, PHC, and CYC handled the cellular studies and molecular analysis and analyzed the data; SJT, JIC, CCW, BMH, HSS, CMC, and SHY designed the experiments and oversaw the progress of the study. IOY, HMC, and SHY drafted the paper. All authors read and approved the final manuscript.

Funding

This work was supported by the Ministry of Science and Technology (MOST 105-2628-B-006-015-MY3, 108-2314-B-006-079-MY3, and MOST 106-2320-B-006-004).

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Correspondence to Shang-Hsun Yang.

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Supplementary Figure 1.
figure7

BAY11-7082 suppresses the expression of NF-kB in Q7 and Q111 cells with the treatment of FGF9. Q7 and Q111 cells were pretreated with BAY11-7082 for 1 h, cultured with or without FGF9 for 48 h, and then subjected to western blotting using NF-kB and γ-tubulin antibodies. γ-tubulin was used as an internal control. (PNG 116 kb)

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Yusuf, I.O., Chen, HM., Cheng, PH. et al. Fibroblast Growth Factor 9 Stimulates Neuronal Length Through NF-kB Signaling in Striatal Cell Huntington’s Disease Models. Mol Neurobiol 58, 2396–2406 (2021). https://doi.org/10.1007/s12035-020-02220-w

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Keywords

  • Fibroblast growth factor 9
  • NF-κB signaling
  • Neuronal length
  • Huntington’s disease