Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF
Background: Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug cand...
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| Hauptverfasser: | , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
20 January 2015
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| In: |
Frontiers in cellular neuroscience
Year: 2015, Jahrgang: 8 |
| ISSN: | 1662-5102 |
| DOI: | 10.3389/fncel.2014.00464 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: http://dx.doi.org/10.3389/fncel.2014.00464 Verlag, kostenfrei, Volltext: http://journal.frontiersin.org/article/10.3389/fncel.2014.00464/full 
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| Verfasserangaben: | Alexandre Henriques, Stefan Kastner, Eva Chatzikonstantinou, Claudia Pitzer, Christian Plaas, Friederike Kirsch, Oliver Wafzig, Carola Krüger, Robert Spoelgen, Jose-Luis Gonzalez De Aguilar, Norbert Gretz and Armin Schneider |
| Zusammenfassung: | Background: Amyotrophic lateral sclerosis (ALS) is an incurable fatal motoneuron disease with a lifetime risk of approximately 1:400. It is characterized by progressive weakness, muscle wasting, and death ensuing 3-5 years after diagnosis. Granulocyte-colony stimulating factor (G-CSF) is a drug candidate for ALS, with evidence for efficacy from animal studies and interesting data from pilot clinical trials. To gain insight into the disease mechanisms and mode of action of G-CSF, we performed gene expression profiling on isolated lumbar motoneurons from SOD1G93A mice, the most frequently studied animal model for ALS, with and without G-CSF treatment. Results: Motoneurons from SOD1G93A mice present a distinct gene expression profile in comparison to controls already at an early disease stage (11 weeks of age), when treatment was initiated. The degree of deregulation increases at a time where motor symptoms are obvious (15 weeks of age). Upon G-CSF treatment, transcriptomic deregulations of SOD1G93A motoneurons were notably restored. Discriminant analysis revealed that SOD1 mice treated with G-CSF has a transcriptom close to presymptomatic SOD1 mice or wild type mice. Some interesting genes modulated by G-CSF treatment relate to neuromuscular function such as CCR4-NOT or Prss12. Conclusions: Our data suggest that G-CSF is able to re-adjust gene expression in symptomatic SOD1G93A motoneurons. This provides further arguments for G-CSF as a promising drug candidate for ALS. |
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| Beschreibung: | Gesehen am 29.08.2017 Volume 8 erstreckt sich über die beiden Jahre 2014 und 2015 Im Titel ist "G93A" hochgestellt |
| Beschreibung: | Online Resource |
| ISSN: | 1662-5102 |
| DOI: | 10.3389/fncel.2014.00464 |