Back to Search
Start Over
Characterizing the multiple roles of FGF‐2 in SOD1 G93A ALS mice in vivo and in vitro
- Source :
- Journal of Cellular Physiology. 234:7395-7410
- Publication Year :
- 2018
- Publisher :
- Wiley, 2018.
-
Abstract
- We have previously shown that knockout of fibroblast growth factor-2 (FGF-2) and potential compensatory effects of other growth factors result in amelioration of disease symptoms in a transgenic mouse model of amyotrophic lateral sclerosis (ALS). ALS is a rapidly progressive neurological disorder leading to degeneration of cortical, brain stem, and spinal motor neurons followed by subsequent denervation and muscle wasting. Mutations in the superoxide dismutase 1 (SOD1) gene are responsible for approximately 20% of familial ALS cases and SOD1 mutant mice still are among the models best mimicking clinical and neuropathological characteristics of ALS. The aim of the present study was a thorough characterization of FGF-2 and other growth factors and signaling effectors in vivo in the SOD1G93A mouse model. We observed tissue-specific opposing gene regulation of FGF-2 and overall dysregulation of other growth factors, which in the gastrocnemius muscle was associated with reduced downstream extracellular-signal-regulated kinases (ERK) and protein kinase B (AKT) activation. To further investigate whether the effects of FGF-2 on motor neuron death are mediated by glial cells, astrocytes lacking FGF-2 were cocultured together with mutant SOD1 G93A motor neurons. FGF-2 had an impact on motor neuron maturation indicating that astrocytic FGF-2 affects motor neurons at a developmental stage. Moreover, neuronal gene expression patterns showed FGF-2- and SOD1 G93A -dependent changes in ciliary neurotrophic factor, glial-cell-line-derived neurotrophic factor, and ERK2, implying a potential involvement in ALS pathogenesis before the onset of clinical symptoms.
- Subjects :
- 0301 basic medicine
Denervation
Genetically modified mouse
Physiology
Clinical Biochemistry
SOD1
Cell Biology
Biology
Ciliary neurotrophic factor
Motor neuron
Fibroblast growth factor
medicine.disease
Cell biology
03 medical and health sciences
030104 developmental biology
0302 clinical medicine
medicine.anatomical_structure
Neurotrophic factors
030220 oncology & carcinogenesis
medicine
biology.protein
Amyotrophic lateral sclerosis
Subjects
Details
- ISSN :
- 10974652 and 00219541
- Volume :
- 234
- Database :
- OpenAIRE
- Journal :
- Journal of Cellular Physiology
- Accession number :
- edsair.doi...........197e3fd6cd555be7849a8e8189ca24a5