Modeling the Prodromal Phase of Parkinson's Disease in the Paraquat and Lectin Rat Model
Caroline Swain1, Khoi Le1, Vaibhavi Peshattiwar1, Dipesh Pokharel1, Kala Venkiteswaran2, Thyagarajan Subramanian3
1Neurology, 2Neurology and Neurosciences, 3Neurology, Neurosciences, and Bioengineering, University of Toledo College of Medicine and Life Sciences
Objective:
To develop a rodent model of Parkinson’s disease which recapitulates REM sleep behavior disorder-like sleep abnormalities, a highly specific risk factor and component of the prodromal phase of Parkinson’s disease. 
Background:
REM sleep is a phase of sleep characterized by rapid eye movement and atonia. REM sleep behavior disorder (RBD) is a clinical condition in humans where atonia is lost during REM sleep, and dream enactment often occurs. RBD represents an important and specific risk factor for the development of Lewy body diseases, such as Parkinson’s disease or Dementia with Lewy bodies. The development of an animal model which recapitulates RBD-like sleep abnormalities prior to the onset of motor deficits is critical for understanding the prodromal phase, and for future research investigating slowing the progression of Parkinson’s disease. 
Design/Methods:
Video polysomnography (vPSG) was used to investigate RBD-like sleep abnormalities in a rat model of Parkinson’s disease in which subthreshold doses of the herbicide paraquat and dietary lectins are orally administered for 90 days. Headcaps were implanted for 24 hour sleep wake recordings of EOG, EEG, and EMG. Analysis of vPSG and motor behaviors were taken every two weeks to capture the progression of sleep abnormalities in relation to motor deficits. 
Results:
Rats show RBD-like sleep abnormalities, characterized by REM sleep without atonia, as early as two weeks following initiation of paraquat and lectin treatment, prior to the onset of motor deficits. 
Conclusions:
The paraquat and lectin rat model holds strong face and construct validity as a model for Parkinson’s disease, recapitulating non-motor aspects of the prodromal phase followed by a steady progression of motor deficits. 
10.1212/WNL.0000000000211205
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