Analysis of neurological disease in four dimensions: insight from ALS- PDC epidemiology and animal models.
The causal factor(s) responsible for sporadic neurological diseases are unknown and the stages of disease progression remain undefined and poorly understood. We have developed an animal model of amyotrophic lateral sclerosis-parkinsonism dementia complex which mimics all the essential features of the disease with the initial neurological insult arising from neurotoxins contained in washed cycad seeds. Animals fed washed cycad develop deficits in motor, cognitive, and sensory behaviors that correlate with the loss of neurons in specific regions of the central nervous system. The ability to recreate the disease by exposure to cycad allows us to extend the model in multiple dimensions by analyzing behavioral, cellular, and biochemical changes over time. In addition, the ability to induce toxin-based neurodegeneration allows us to probe the interactions between genetic and epigenetic factors. Our results show that the impact of both genetic causal and susceptibility factors with the cycad neurotoxins are complex. The article describes the features of the model and suggests ways that our understanding of cycad-induced neurodegeneration can be used to decipher and identify the early events in various human neurological diseases.[1]References
- Analysis of neurological disease in four dimensions: insight from ALS-PDC epidemiology and animal models. Shaw, C.A., Wilson, J.M. Neuroscience and biobehavioral reviews. (2003) [Pubmed]
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