Fibroblast Growth Factor 9 Stimulates Neuronal Length Through NF-kB Signaling in Striatal Cell Huntington’s Disease Models
- 9 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Molecular Neurobiology
- Vol. 58 (5), 2396-2406
- https://doi.org/10.1007/s12035-020-02220-w
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.Keywords
Funding Information
- Ministry of Science and Technology, Taiwan (MOST 105-2628-B-006-015-MY3, 108-2314-B-006 -079 -MY3 and MOST 106-2320-B-006-004)
This publication has 57 references indexed in Scilit:
- Dysregulation of synaptic proteins, dendritic spine abnormalities and pathological plasticity of synapses as experience-dependent mediators of cognitive and psychiatric symptoms in Huntington’s diseaseNeuroscience, 2013
- Synapses and Dendritic Spines as Pathogenic Targets in Alzheimer’s DiseaseNeural Plasticity, 2012
- Interaction between NF-κB signaling and Notch signaling in gliogenesis of mouse mesencephalic neural crest cellsMechanisms of Development, 2011
- FGF2 gene transfer restores hippocampal functions in mouse models of Alzheimer's disease and has therapeutic implications for neurocognitive disordersProceedings of the National Academy of Sciences of the United States of America, 2011
- Regulation of miR-146a by RelA/NFkB and p53 in STHdhQ111/HdhQ111 Cells, a Cell Model of Huntington's DiseasePLOS ONE, 2011
- Regulation of neural process growth, elaboration and structural plasticity by NF-κBTrends in Neurosciences, 2011
- Dendritic vulnerability in neurodegenerative disease: insights from analyses of cortical pyramidal neurons in transgenic mouse modelsBrain Structure and Function, 2010
- Nuclear Factor κB Signaling Regulates Neuronal Morphology and Cocaine RewardJournal of Neuroscience, 2009
- Analysis of gene expression during neurite outgrowth and regenerationBMC Neuroscience, 2007
- Inhibitors of NF-κB signaling: 785 and countingOncogene, 2006