Early Exposure to Environmental Toxin Contributes to Neuronal Vulnerability and Axonal Pathology in a Model of Familial ALS.docVIP

Neuroscience Medicine, 2012, 3, 404-417 /10.4236/nm.2012.34050 Published Online December 2012 (http://www.SciRP.org/journal/nm) Early Exposure to Environmental Toxin Contributes to Neuronal Vulnerability and Axonal Pathology in a Model of Familial ALS Grace Lee , Christopher A. Shaw 1,2 1,2,3 1 Department of Experimental Medicine, University of British Columbia, Vancouver, Canada; 2 Department of Ophthalmology and Visual Sciences, University of British Columbia, Vancouver, Canada; Vancouver, Canada. 3 Department of Neuroscience, University of British Columbia, Email: cashawlab@ Received September 13 , 2012; revised October 18 , 2012; accepted November 4 , 2012 th th th ABSTRACT Adult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the cen- tral nervous system, specifically the loss of motor neurons. Sporadic ALS causality is not well understood, but is almost certainly of multifactorial origin involving a combination of genetic and environmental factors. The discovery of en- demic ALS in the native Chamorro population of Guam during the 1950s and the co-occurrence of Parkinsonism and dementia in some patients led to searches for environmental toxins that could be responsible. In the present paper, we report that an environmental neurotoxin enhances mutant superoxide dismutase (SOD)-induced spinal motor neuron death and pathology and induces motor axon abnormalities. These results cumulatively confirm earlier findings that exposure to an environmental toxin is sufficient to produce the disease phenotype and indicate a role for gene-envi- ronment interaction in some forms of the disease. Keywords: SOD1; ALS; Neurotoxin; Axonopathy; NMJ; Gliosis; Toxicity 1. Introducti