Characterizing the multiple roles of FGF-2 in SOD1G93A ALS mice in vivo and in vitro

被引:6
|
作者
Kefalakes, Ekaterini [1 ,2 ]
Boeselt, Sebastian [1 ]
Sarikidi, Anastasia [1 ]
Ettcheto, Miren [3 ,4 ,5 ,6 ]
Bursch, Franziska [1 ,2 ]
Naujock, Maximilian [1 ,2 ]
Stanslowsky, Nancy [1 ,2 ]
Schmuck, Martin [7 ]
Barenys, Marta [8 ,9 ]
Wegner, Florian [1 ,2 ]
Grothe, Claudia [2 ,10 ]
Petri, Susanne [1 ,2 ]
机构
[1] Hannover Med Sch, Dept Neurol, Carl Neuberg Str 1, D-30625 Hannover, Germany
[2] Ctr Syst Neurosci ZSN, Hannover, Germany
[3] Univ Barcelona, Fac Pharm & Food Sci, Dept Pharmacol Toxicol & Therapeut Chem, Barcelona, Spain
[4] Biomed Res Networking Ctr Neurodegenerat Dis CIBE, Madrid, Spain
[5] Univ Barcelona, Inst Neurosci, Barcelona, Spain
[6] Univ Rovira & Virgili, Fac Med & Life Sci, Dept Biochem, Reus, Spain
[7] Univ Calif Davis, Davis Sch Vet Med, Davis, CA 95616 USA
[8] Univ Barcelona, INSA UB, GRET, Barcelona, Spain
[9] Univ Barcelona, Fac Pharm, Pharmacol Toxicol & Therapeut Chem Dept, Toxicol Unit, Barcelona, Spain
[10] Hannover Med Sch, Inst Neuroanat & Cell Biol, Hannover, Germany
关键词
AKT; amyotrophic lateral sclerosis (ALS); astrocytes; extracellular-signal-regulated kinase (ERK); fibroblast growth factor-2 (FGF-2); glial-cell-line-derived neurotrophic factor (GDNF); motor neurons; superoxide dismutase 1 (SOD1); FIBROBLAST-GROWTH-FACTOR; FACTOR BFGF INJECTION; SPINAL-CORD; MOUSE MODEL; CELL-PROLIFERATION; SKELETAL-MUSCLE; MOTOR-NEURONS; FACTOR-2; SURVIVAL; EXPRESSION;
D O I
10.1002/jcp.27498
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 SOD1(G93A) 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.
引用
收藏
页码:7395 / 7410
页数:16
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