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

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• Neuronal development is crucial for brain function; its impairment can lead to neurodevelopmental disorders.
• Huntington's disease (HD) is a neurodegenerative disorder marked by neuronal structure deficits, neuronal death, and central nervous system dysfunction.
• Fibroblast growth factors (FGFs), including FGF9, have shown potential neuroprotective effects and can promote neuronal development and neurite outgrowth, but their role in HD neuronal morphology remains unclear.

Purpose of the Study:

• To investigate the effects of FGF9 on neuronal length in Huntington's disease (HD) models.
• To elucidate the underlying molecular mechanisms by which FGF9 influences neuronal morphology in HD.

Main Methods:

• Utilized striatal cell lines derived from HD knock-in mice.
• Assessed the impact of FGF9 on total neuronal length and the expression of structural and synaptic proteins.
• Investigated the role of nuclear factor kappa B (NF-kB) signaling pathway activation by FGF9.

Main Results:

• FGF9 treatment significantly increased total neuronal length in HD cell lines.
• FGF9 upregulated key structural and synaptic proteins under HD conditions.
• FGF9 activated the NF-kB signaling pathway, and blocking NF-kB suppressed FGF9-induced protein upregulation.

Conclusions:

• FGF9 enhances total neuronal length in HD models, potentially through the upregulation of NF-kB signaling.
• The activation of NF-kB signaling by FGF9 contributes to the observed increases in structural and synaptic proteins.
• This FGF9-mediated mechanism involving NF-kB activation may represent a significant pathway for neuroprotection in Huntington's disease.