Abstract
As the most common genetic cause of Parkinson's disease (PD), the role of human leucine-rich repeat kinase 2 (hLRRK2) in the efficacy of PD treatment is a focus of study. Our previous study demonstrated that mushroom body (MB) expression of hLRRK2 in Drosophila could recapitulate the clinical feature of sleep disturbances observed in PD patients, and melatonin (MT) treatment could attenuate the hLRRK2-induced sleep disorders and synaptic dysfunction, suggesting the therapeutic potential of MT in PD patients carrying hLRRK2 mutations; however, no further study into the impacts on memory deficit was conducted. Therefore, in the current paper, the study of the effects of MT on hLRRK2 flies was continued, to determine its potential role in the improvement of memory deficit in PD. To achieve this, the Drosophila learning and memory phases, including short- and long-term memory, were recorded; furthermore, the effect of MT on calcium channel activity during neurotransmission was detected using electrophysiology patch clamp recordings. It was demonstrated that MT treatment reversed hLRRK2-induced long-term memory deficits in Drosophila; furthermore, MT reduced MB calcium channel activities. These findings suggest that MT may exerts therapeutic effects on the long-term memory of PD patients via calcium channel modulation, thus providing indication of its potential to maintain cognitive function in PD patients.
