Protective effects of β- nicotinamide adenine dinucleotide against motor deficits and dopaminergic neuronal damage in a mouse model of Parkinson's disease

Publication date: Available online 17 June 2019Source: Progress in Neuro-Psychopharmacology and Biological PsychiatryAuthor(s): Chang Shan, Yan-ling Gong, Qian-qian Zhuang, Yan-fang Hou, Shu-min Wang, Qin Zhu, Guo-rui Huang, Bei Tao, Li-hao Sun, Hong-yan Zhao, Sheng-tian Li, Jian-min LiuAbstractThe level of nicotinamide adenine dinucleotide (NAD) decreases in Parkinson's disease (PD), and its reduction has been reported to be involved in many age-associated neurodegenerative pathologies. Thus, we investigated whether NAD replenishment is beneficial in a 6-hydroxydopamine (6-OHDA)-induced mouse model of PD. Preinjection with NAD in the striatum ameliorated motor deficits and dopaminergic neuronal damage in the substantia nigra and striatum of a mouse model of PD. Moreover, preincubation with NAD protected PC12 cells against the loss of cell viability, morphological damage, oxidative stress and mitochondrial dysfunction caused by 6-OHDA. These results add credence to the beneficial role of NAD against parkinsonian neurodegeneration in mouse models of PD, provide evidence for the potential of NAD for the prevention of PD, and suggest that NAD prevents pathological changes in PD via decreasing mitochondrial dysfunctions.
Source: Progress in Neuro Psychopharmacology and Biological Psychiatry - Category: Psychiatry Source Type: research

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Source: Journal of Molecular Biology - Category: Molecular Biology Source Type: research
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Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: Review Source Type: research
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Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
In this study, astrocytic Kir6.1 knockout (KO) mice were used to examine the effect of astrocytic Kir6.1/K-ATP channel on dopaminergic (DA) neurodegeneration triggered by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Here, we found that astrocytic Kir6.1 KO mice showed more DA neuron loss in substantia nigra compacta (SNc), lower level of dopamine in the striatum, and more severe motor dysfunction than controls. Interestingly, this companied by increased neuroinflammation and decreased autophagy level in SNc in vivo and astrocytes in vitro. Mechanistically, astrocytic Kir6.1 KO inhibited mitophagy which resu...
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Source: Mitochondrion - Category: Biochemistry Source Type: research
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