A novel rat model of body first subtype of Parkinson's disease

The recent growing evidence support the existence of two subtypes of Parkinson's disease (PD), a body first and brain first subtype owing to variability in the disease site of onset as well as disease progression. Animal models which could replicate the specific differences of these subtypes are important to explore the pathophysiology as well as to evaluate novel treatment options. Here, we describe an animal model of body first PD subtype developed using repeated low dose exposure of environmental neurotoxin Paraquat (P) and Lectin (L) to characterize its PD-like manifestations. We administered P+L (P+L, p.o.) daily to rats for 90 days. These animals underwent motor and non-motor behavioral tests at various time intervals. After 21 weeks, post-mortem histopathological analysis was performed to assess neurodegeneration. Onset of motor deficits initiated unilaterally from week 4 of P+L followed by gradual progression towards bilateral symptoms that were levodopa responsive. This model also replicates non motor features including cognitive deficits in tests like Novel Object Recognition Test and Y maze as well as sleep abnormalities. The histopathology showed nigrostriatal dopaminergic degeneration and proteinase K resistant S129 alpha-synucleinopathy both in the gut and the brain. The replication of both progressive motor and non-motor features in this rat model corroborates body first subtype of PD therefore making it an attractive option for testing neuroprotective experimental therapeutics and avenue to understand pathophysiological mechanisms.