Novel Observation-Based Criteria for Sleep-Wake Classification in a Preclinical Model of Sleep Disorder

OBJECTIVE: Assess a behavior-based criteria for determining rat wake-sleep stages in an animal model of REM sleep disorder (RBD) and its correlation with clinical phenomenology.BACKGROUND: RBD is a non-motor symptom associated with Parkinson’s disease (PD), characterized by motor phenomenology and absence of atonia during REM sleep. The pathophysiology of RBD is not fully elucidated and preclinical models of RBD have not been behaviorally adequately characterized to correlate with the phenomenology seen in patients with RBD.DESIGN/METHODS: We recently demonstrated that the hemiparkinsonian (HP) rat model of PD exhibited RBD-like features (Vo et. al., 2014). Here we characterize the RBD associated motor phenomenology using 1-hour recordings of 10 normal and 5 HP rats using 6 behavioral hallmarks seen on video sleep recordings scored by blinded raters with excellent inter-rater reliability. Scores were correlated to time-locked polysomnography (PSG) that was rated independently.RESULTS: In normal rats, there is good agreement between the behavior-based criteria and PSG in all raters (all Concordance correlation coefficient CCC ˃ 0.8), with the sleep-wake profiles showing a close match. In HP rats, there is relatively poor agreement (CCC u003c 0.8).CONCLUSIONS: Our findings suggest that the behavioral-based video criteria is able to classify the sleep-wake state of the normal rodent with accuracy comparable to that of PSG. In HP rats, we observed behavioral changes during REM sleep which, when used with PSG gives a better clinical correlate of RBD in PD. This study provides first proof of principle of a rat model of RBD and PD that could be used for pathophysiological and translational therapeutic studies.Study Supported by: R01NS42402, R21AT001607, DIBTH0632 Disclosure: Dr. Vo has nothing to disclose. Dr. Mell has nothing to disclose. Dr. Iyer has nothing to disclose. Dr. Venkiteswaran has nothing to disclose. Dr. Chinniah has nothing to disclose. Dr. Fang has nothing to disclose. Dr. Subramanian has received personal compensation for activities with Teva, USMedWorld, UCB Pharma as a speaker board member.