The Parkinson's-Reversing Breakthrough

Treatment for Parkinson Disease

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The incidence of neurodegenerative disorders in nonhuman animals is rare, likely due to the selective pressures to remove affected animals from the population. However, the identification of spontaneous occurrences or the induction of specific phe-notypes in a variety of animal species provides an important foundation to study neurological disorders and are critical for determining underlying disease mechanisms and developing new therapeutic modalities. In general, the utility of an animal model for a particular disease is often dependent on how closely the model replicates all or part of the human condition. In Parkinson's disease (PD) and related parkinsonian disorders, there now exists a variety of animal models, each of which makes a unique contribution to our understanding of the human condition. These models have been derived in a variety of species (i.e., pig, nonhuman primate, rodent, and cat) using multiple techniques, including pharmacological manipulation, administration of neurotoxicants, genetic models, and surgical lesioning. Although these models are not identical to the human condition with respect to behavioral characteristics, brain anatomy, or disease progression, they have provided significant advancements in our understanding of the underlying mechanisms and treatment of movement disorders, such as PD.

PD is characterized by bradykinesia, rigidity, postural instability, and resting tremor. The primary pathological and biochemical features of PD are the loss of nigrostriatal dopaminergic neurons in the substantia nigra pars compacta (SNpc), the appearance of intracellular inclusions called Lewy bodies, and the depletion of striatal dopamine. Clinical features are apparent when striatal dopamine depletion reaches 80% despite the fact that 45% to 60% of nigrostriatal dopaminergic neurons still remain (1). Other regions of the brain and other nondopaminergic neurotrans-mitter systems are also affected in PD, which must be taken into consideration in animal model development. Since the destruction of the nigrostriatal system and consequent depletion of striatal dopamine are key features in the human condition, attempts have been made in animal models to disrupt an analogous anatomical area through surgical, pharmacological, or neurotoxicant manipulation.

The purpose of this chapter is to introduce the many different animal models utilized in PD research. Despite the fact that many of the animal models used are generated through acute intervention, although PD is a progressive neurode-generative disorder, should not diminish their importance and potential impact. Recently, several toxin-induced, spontaneous, and transgenic models have been shown to display progressive motor deficits and/or degeneration. In this chapter, the most common models are discussed with respect to development, behavioral profile, biochemical and neuropathological alterations, and contribution to the field.

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