The role of orexin and dopamine in sleep alterations from the progressive, neurotoxin‐induced model of parkinsonism

Abstract

Parkinson's disease (PD) is classically defined as a motor disorder resulting from decreased dopamine (DA) production in the basal ganglia circuit. To better diagnose PD before the onset of severe motor dysfunction, current attention has focused on the early, non‐motor symptoms. Sleep disorders, such as excessive daytime sleepiness (EDS), are one of the most prominent initial symptoms in PD. Recent studies revealed that orexin (ORX) neurons, a cell type vital to sleep regulation, also degenerate in PD and may contribute to the sleep disorders. We have developed a novel, progressive rat model that can investigate this aspect of PD. Epidemiological studies found a link between the Guamanian variant of Amyotrophic Lateral Sclerosis/Parkinsonism Dementia Complex (ALS/PDC) and the consumption of flour made from the washed seeds of the plant, Cycas micronesica (cycad). Cycad‐fed rats displayed a parkinsonian phenotype. Uniquely, these rats also displayed a hypersomnolent behavior similar to EDS and a significant loss of ORX neurons. We hypothesize that the sleep disturbance is due to orexin dysfunction, which then induces a loss of DA neurons in the SN. To measure this altered neurochemistry, we utilized microdialysis and high performance liquid chromatography to determine levels of DA in the SN and caudate putamen of the cycad‐fed rat.Support: NIEHS (KM); NIDA (SF); VA (PY)Grant Funding Source: NIEHS