AUTHOR=Henriques Alexandre , Kastner Stefan , Chatzikonstantinou Eva , Pitzer Claudia , Plaas Christian , Kirsch Friederike , Wafzig Oliver , Krüger Carola , Spoelgen Robert , Gonzalez De Aguilar Jose-Luis , Gretz Norbert , Schneider Armin
TITLE=Gene expression changes in spinal motoneurons of the SOD1G93A transgenic model for ALS after treatment with G-CSF
JOURNAL=Frontiers in Cellular Neuroscience
VOLUME=8
YEAR=2015
URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2014.00464
DOI=10.3389/fncel.2014.00464
ISSN=1662-5102
ABSTRACT=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.