Abstract
AbstractAdult onset amyotrophic lateral sclerosis (ALS) arises due to progressive and irreversible functional deficits to the central 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 endemic 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 an 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-environment interaction in some forms of the disease.
Highlights
While studies that focus on putative environmental toxins are relatively few, to date those that seek to find the link between toxins and genetic susceptibility are rarer[12]
While steryl glucosides (SG)-fed female wild types showed a decline in latency to fall compared to controls, this effect started after 40 weeks of age and was not significant (F = 1.86, p = 0.17)
The results of the present study demonstrate the contribution of an identified neurotoxin linked to some forms of amyotrophic lateral sclerosis (ALS) to the progression of motor deficits and neurodegenerative processes of a mouse model of ALS
Summary
While studies that focus on putative environmental toxins are relatively few, to date those that seek to find the link between toxins and genetic susceptibility are rarer[12]. Following 70 days of cycad feeding, quantitative magnetic resonance imaging in adult CD-1 mice showed decreased volumes in lumbar cord grey matter, substantia nigra, striatum, motor cortex, and basal nuclei[26] These studies indicated a primarily neurotoxic etiology to ALS-PDC. Based on the above studies using cycad seed flour or the derived toxins, we tested the hypothesis that similar toxins could modify the onset and progression of disease symptoms in SOD1 transgenic mice. To explore this hypothesis, the current study distinguished between the pathological consequences of either genetic predisposition to neurodegeneration or neurotoxin acting alone on motor axons, and the site of primary pathogenesis when both stressors act in combination
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