The BSSG rat model of Parkinson's disease: progressing towards a valid, predictive model of disease

Parkinson's disease (PD) is a neurodegenerative disorder, classically considered a movement disorder. A great deal is known about the anatomical connections and neuropathology and pharmacological changes of PD, as they relate to the loss of dopaminergic function and the appearance of cardinal motor symptoms. Our understanding of the role of dopamine in PD has led to the development of effective pharmacological treatments of the motor symptoms in the form of dopamine replacement therapy using levodopa and dopaminergic agonists. Much of the information concerning these drug treatments has been obtained using classical neurotoxic models that mimic dopamine depletion (e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or MPTP, 6-hydroxydopamine, reserpine). However, PD is more than a disorder of the nigrostriatal dopamine pathway. Our understanding of the neuropathology of PD has undergone massive changes, with the discovery that mutations in alpha-synuclein cause a familial form of PD and that PD pathology may spread, affecting multiple neurotransmitter systems and brain regions. These new developments in our understanding of PD demand that we reconsider our animal models. While classic neurotoxin models have been useful for the development of effective symptomatic treatments for motor manifestations, the paucity of a valid animal model exhibiting the progressive development of multiple key features of PD pathophysiology and phenotype has impeded the search for neuroprotective therapies, capable of slowing or halting disease progression. Relevance of the article for predictive, preventive and personalised medicine What characteristics would a good animal model of human PD have? In so much as is possible, a good model would exhibit as many behavioral, anatomical, biochemical, immunological, and pathological changes as are observed in the human condition, developing progressively, with clear, identifiable biomarkers along the way. Here, we review the BSSG rat model of PD, a novel environmental model of PD, with strong construct, face, and predictive validity. This model offers an effective tool for the screening of preventive therapies that may prove to be more predictive of their effects in human patients.