Review
Insights into Parkinson's disease models and neurotoxicity using non-invasive imaging

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Abstract

Loss of dopamine in the nigrostriatal system causes a severe impairment in motor function in patients with Parkinson's disease and in experimental neurotoxic models of the disease. We have used non-invasive imaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (MRI) to investigate in vivo the changes in the dopamine system in neurotoxic models of Parkinson's disease. In addition to classic neurotransmitter studies, in these models, it is also possible to characterize associated and perhaps pathogenic factors, such as the contribution of microglia activation and inflammatory responses to neuronal damage. Functional imaging techniques are instrumental to our understanding and modeling of disease mechanisms, which should in turn lead to development of new therapies for Parkinson's disease and other neurodegenerative disorders.

Section snippets

Neurotoxic models of Parkinson's disease

The capacity of a number of pharmacological agents and environmental toxins to lesion specific neural populations has been used extensively to mimic the pathological and functional alterations that characterize neurodegenerative disorders. These experimental models are useful for the evaluation of therapeutic strategies directed to obtain symptomatic relief and to slow down the degenerative process (neuroprotection). On the basis of experimental and clinical findings, Parkinson's disease (PD)

In vivo functional imaging of DA neurotoxicity

Functional neuroimaging techniques such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) make it possible to evaluate in vivo specific neural circuits in the brain before and after administration of a neurotoxin. Predictive models of disease progression are required for testing disease-modifying hypothesis and for this purpose non-invasive imaging techniques can play a fundamental role (Brownell et al., 1998a, Brownell et al., 1999). Studies combining the

Conclusions

In summary, current methodology using non-invasive imaging techniques allows detailed in vivo investigation of the DA system in normal and disease states. It is possible to quantify the extent of DA neuronal loss, the development of compensatory changes, and the involvement of other (non-DA) brain regions. These studies are important to estimate biological variables like the rate of progression of the disease, in order to evaluate the impact of therapeutic and neuroprotective interventions. In

Acknowledgments

This work is supported by NIH Udall Parkinson's Disease Research Center Grant (P50 NS39793), NIH grant (R01 NS41263), USAMRMC grant (DAMD17-01-1-0762) to OI, and P51 RR00168. The support of the Kinetics Foundation, the Parkinson's Foundation National Capital Area, the Consolidated Anti-Aging Foundation, the Orchard Foundation, and the Michael Stern Foundation is also gratefully acknowledged.

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