Sleep Alteration in an Environmental Neurotoxin Induced Model of Parkinson's Disease

Abstract

Parkinson's disease (PD) is defined as a motor disorder resulting from decreased dopamine in the basal ganglia circuit. However, research now focuses on early, non‐motor symptoms of PD, such as sleep disturbances, in an attempt to diagnose the disease before the loss of motor function. A sleep alteration commonly found in PD patients is Excessive Daytime Sleepiness (EDS), whose etiology and connection to PD is relatively unknown. Few animal models are able to replicate both motor and non‐motor symptoms of PD. Here, we present a progressive rat model of PD that displays the degeneration in motor function and disturbances in sleep. Our study examined the effects of prolonged consumption of flour made from washed seeds of the Cycas micronesia (cycad) in male rats. A novel behavior observed was the increase in purposeless chewing, a form of stereotypy. It was demonstrated that cycad‐fed rats exhibited a sleep disturbance, shown by an increase in length and number of bouts of rapid eye movement (REM) sleep during the active period. This increase in REM parallels the symptom of EDS. We are now examining the etiology of EDS in the cycad‐fed rats. Preliminary results suggest a key role for the lateral hypothalamus in the development of this early, non‐motor symptom. This also reveals a potential mechanism of action for the toxic effects of cycad in brain areas other than those of the basal ganglia motor circuit.