S RAMBOZ, K CIRILLO, R SPRINGER, M MAZZELLA, M WINDISCH, K WALKER
Numerous genetic and pharmacological animal models have been generated to mimic different aspects of Parkinson’s disease, a neurodegenerative disorder estimated to affect more than 1% of the over-65 population. Parkinson’s disease is associated with the loss of nigral dopaminergic cells leading to a decline in dopamine levels. Due to this observation, depletion of nigral dopaminergic cells using lesion models have been developed and used to investigate the basis of symptomatic treatment. In the last couple of years, PsychoGenics has established and validated lesions models of MPTP and 6OHDA which are broadly used to assess neuroprotective drug treatments. Like any model, the lesions have a down side, provoking a very rapid loss of dopaminergic neurons, which would have taken decades in human. Slow cell loss and dopamine depletion would allow some compensatory mechanisms to take place, which might be not present in the lesion models. Recently, PsychoGenics licensed a well described and validated genetically modified -synuclein mouse line from Prof. Masliah’s laboratory at UCSD: Line 61. This line is -synuclein transgenic mouse model expressing the human -synuclein cDNA under the murine Thy-1 promoter . Line 61 presents most of the characteristics of parkinsonism symptoms, including lack of coordination at 4 months, cognition deficit at 4.5 months, increased of total activity in open field by 7 months, hypolocomotion by 14 months and presence of -synuclein positive aggregates. By 9 months of age, accumulation of phosphorylated Serine 129 residues in striatum and substantia nigra which might modulate the formation of protein aggregation likes inclusion bodies and fibrils. We are assessing the line 61 animal model using PsychoGenics proprietary technologies (SmartCube®, PhenoCube® and NeuroCube®) to retrieve early onset phenotype and establish high throughput preclinical readouts.