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New Mouse Model Mimics Neuron Loss in Parkinsonís Disease
- Oct 16 2012
Scientists have developed a new mouse model for Parkinson’s disease (PD) that may allow them to better study how the disease progresses and to test new therapies. The study, funded in part by the Parkinson’s Disease Foundation, appeared in the September 25 issue of Proceedings of the National Academy of Sciences USA.
To study and understand disease, scientists create animal models that mimic the effects of diseases as they occur in people. However, due to the complexity of the human brain when compared to mice and rats, the use of animal models in PD is problematic. The animals often do not truly mimic the features of the disease.
A team led by David S. Park, Ph.D., at the University of Ottawa, may have discovered a new and more effective mouse model. They were studying an existing mouse model, a strain of mice with a mutation in the DJ-1 gene, which in people can cause an extremely rare form of early-onset PD. But the mouse model was not ideal because mice did not seem to lose dopamine neurons in their brains, a key sign of PD in people. While the researchers were studying those mice, they mated them with another strain of mice, which unexpectedly produced offspring that showed signs and symptoms of Parkinson’s disease.
- Some of the new mice showed dramatic, early-onset loss of dopaminergic neurons in a region of the brain called the substantia nigra, the same brain region affected in people with Parkinson’s disease.
- The pattern in which the mice lost neurons mimicked the pattern observed in people with Parkinson’s. Initially, the mice lost neurons on only one side of the brain. As the mice aged, they lost neurons on both sides of the brain.
- Scientists did not observe any Lewy bodies or signs of α-synuclein accumulation (a hallmark of Parkinson’s disease).
- In old age, the mice that experienced neuron loss showed mild motor symptoms similar to those of early Parkinson’s disease.
- When the researchers studied the DNA of PD-affected and unaffected mice, they found that several genetic sequences varied slightly between the two groups. This finding may explain why only some of the mice showed signs and symptoms of PD.
What Does It Mean?
Many advances in medical research in the past century were achieved by using animal models of human diseases. One of the biggest challenges of brain research is that animal models are often inadequate in imitating the human brain function and pathology.
Currently available mice models of Parkinson’s disease include mice that are treated with toxins targeting dopamine cells in the brain and genetic models, in which mice are engineered to carry mutations linked to PD. Both types of models are extremely helpful in PD research but neither one is adequate enough in imitating the disease.
The advantage of the genetic model of PD described in this study is that it represents a progressive disease, which – similar to Parkinson's disease in people – often starts in one side of the brain and progresses to the other side. A disadvantage of the model is that the typical change in brains affected by Parkinson’s disease, the Lewy bodies, are not present in this mouse model. No animal model is perfect. The affected mice showed only mild symptoms of PD, even in old age. This observation suggests differences between the mouse model and people with PD that could result, in part, from the much shorter life span of mice (about 24 months). As a result, these mice may be best suited for studying early stages of PD.
The new mouse model might help identify additional causes and treatments for PD. For example, the researchers plan to further explore the genetic differences between the mice that undergo neurodegeneration and those that do not. These studies may provide clues as to how genes interact with each other to cause PD.
Reference: Rousseaux, M. W. C., Marcogliese, P. C., Qu, D., Hewitt, S. J., Seang, S., Kim, R. H., Slack, R. S., et al. (n.d.). Progressive dopaminergic cell loss with unilateral-to-bilateral progression in a genetic model of Parkinson disease. pnas.org. doi:10.1073/pnas.1205102109
Interested in learning more about how genetics can help scientists study Parkinson's? View PDF's recent PD ExpertBriefing, "What's News in Genetics and Parkinson's Disease?"
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Source Date: Oct 16 2012