Melatonin attenuates hLRRK2‑induced long‑term memory deficit in a Drosophila model of Parkinson's disease

Ran,Dongzhi; Xie,Baogang; Gan,Zongjie; Sun,Xicui; Gu,Huaiyu; Yang,Junqing

doi:10.3892/br.2018.1125

Melatonin attenuates hLRRK2‑induced long‑term memory deficit in a Drosophila model of Parkinson's disease

Authors:
- Dongzhi Ran
- Baogang Xie
- Zongjie Gan
- Xicui Sun
- Huaiyu Gu
- Junqing Yang
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Affiliations: Department of Pharmacology, Chongqing Medical University, The Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, P.R. China, Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, MD 21042, USA, Department of Anatomy and Neurobiology, Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou 510080, P.R. China
Published online on: July 5, 2018 https://doi.org/10.3892/br.2018.1125
Pages: 221-226

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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.

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