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Circadian disruption promotes the neurotoxicity of oligomeric alpha-synuclein in mice

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机构: [1]Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 215004 Suzhou, China. [2]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, 215123 Suzhou, China. [3]Department of Neurology, Xiongan Xuanwu Hospital, 071700 Xiongan, China
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Circadian disruption often arises prior to the onset of typical motor deficits in patients with Parkinson's disease (PD). It remains unclear whether such a prevalent non-motor manifestation would contribute to the progression of PD. Diffusible oligomeric alpha-synuclein (O-αSyn) is perceived as the most toxic and rapid-transmitted species in the early stages of PD. Exploring the factors that influence the spread and toxicity of O-αSyn should be helpful for developing effective interventions for the disease. The aim of this study was to explore the effects of circadian disruption on PD pathology and parkinsonism-like behaviors in a novel mouse model induced by O-αSyn. We discovered that O-αSyn could enter the brain rapidly following intranasal administration, resulting in the formation of nitrated-αSyn pathology and non-motor symptoms of the mice. Meanwhile, circadian disruption exacerbated the burden of nitrated-αSyn pathology and accelerated the loss of dopaminergic neurons in O-αSyn-treated mice. Subsequent experiments demonstrated that circadian disruption might act via promoting nitrative stress and neuroinflammation. These findings could highlight the circadian rhythms as a potential diagnostic and therapeutic target in early-stage PD.© 2024. The Author(s).

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大类 | 1 区 医学
小类 | 1 区 神经科学
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大类 | 1 区 医学
小类 | 1 区 神经科学
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Q1 NEUROSCIENCES
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Q1 NEUROSCIENCES

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第一作者机构: [1]Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 215004 Suzhou, China. [2]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, 215123 Suzhou, China.
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通讯机构: [1]Department of Neurology and Clinical Research Center of Neurological Disease, The Second Affiliated Hospital of Soochow University, 215004 Suzhou, China. [2]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience, Soochow University, 215123 Suzhou, China. [3]Department of Neurology, Xiongan Xuanwu Hospital, 071700 Xiongan, China
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