ALS-Linked SOD1 Mutants Enhance Neurite Outgrowth and Branching in Adult Motor Neurons
Zachary Osking,
Jacob I. Ayers,
Ryan Hildebrandt,
Kristen Skruber,
Hilda Brown,
Daniel Ryu,
Amanda R. Eukovich,
Todd E. Golde,
David R. Borchelt,
Tracy-Ann Read,
Eric A. Vitriol
Affiliations
Zachary Osking
Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA
Jacob I. Ayers
Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
Ryan Hildebrandt
Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, FL 32610, USA
Kristen Skruber
Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA
Hilda Brown
Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USA
Daniel Ryu
Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USA
Amanda R. Eukovich
Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA
Todd E. Golde
Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
David R. Borchelt
Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; Center for Translational Research in Neurodegenerative Disease, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA
Tracy-Ann Read
Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA; Corresponding author
Eric A. Vitriol
Department of Anatomy and Cell Biology, University of Florida, Gainesville, FL 32610, USA; Corresponding author
Summary: Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disease characterized by motor neuron cell death. However, not all motor neurons are equally susceptible. Most of what we know about the surviving motor neurons comes from gene expression profiling; less is known about their functional traits. We found that resistant motor neurons cultured from SOD1 ALS mouse models have enhanced axonal outgrowth and dendritic branching. They also have an increase in the number and size of actin-based structures like growth cones and filopodia. These phenotypes occur in cells cultured from presymptomatic mice and mutant SOD1 models that do not develop ALS but not in embryonic motor neurons. Enhanced outgrowth and upregulation of filopodia can be induced in wild-type adult cells by expressing mutant SOD1. These results demonstrate that mutant SOD1 can enhance the regenerative capability of ALS-resistant motor neurons. Capitalizing on this mechanism could lead to new therapeutic strategies. : Biological Sciences; Genetics; Neuroscience; Cell Biology Subject Areas: Biological Sciences, Genetics, Neuroscience, Cell Biology
