Dietary nicotinamide riboside alleviates motor symptoms in a mouse model of Parkinson’s disease

FARE Award Winner

Authors

• S Devasundaram
• M Rosati
• C Bergamaschi
• J Bear
• R Burns
• P Homan
• MA Dimopoulos
• E Terpos
• GN Pavlakis
• BK Felber

Abstract

Parkinson’s Disease (PD) is a neurodegenerative disorder featuring the progressive loss of nigral dopamine (DA) neurons and a cohort of motor and non-motor symptoms. Age and environmental exposure-induced mitochondrial dysfunction is believed to be one of main mechanisms underlying the neurodegeneration. Nicotinamide riboside (NR), a NAD+ precursor, is a dietary supplement that has been suggested to be beneficial via promoting mitochondrial function, biogenesis, and conversion of nutrients to energy. The overarching goal of this study is to explore whether NR can ameliorate PD symptoms in a mouse model. We created a “double-hit” PD model by overexpressing α-synuclein A53T in Substantia Nigra (SNc) DA neurons and exposed the mice to fungicide benomyl via diet. Longitudinal behavior analysis revealed that chronic NR supplementation via drinking water rescued the motor deficits in PD mice both in rotarod and open field tests but did not rescue the loss of DA neurons. In vivo fiber photometry measurements of ATP/ADP ratio and dopamine release using genetically encoded fluorescent sensors showed that NR increased the ATP/ADP ratio in multiple types of neurons in the brain and elevated the levels of tonic and evoked DA release in the striatum. These results suggest that NR treatment improves the overall mitochondrial function in neurons and promotes DA release, which may provide beneficial effects in PD patients.

Scientific Focus Area: Neuroscience

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