多巴胺能
神经退行性变
黑质纹状体通路
神经科学
星形胶质增生
帕金森病
多巴胺能途径
糖尿病
医学
内科学
多巴胺
内分泌学
黑质
生物
疾病
中枢神经系统
作者
Jean‐François Renaud,Valentina Bassareo,Jimmy Beaulieu,Annalisa Pinna,Michele Schlich,Claude Lavoie,Daniela Murtas,Nicola Simola,Maria-Grazia Martinoli
标识
DOI:10.1016/j.neurobiolaging.2018.05.010
摘要
Epidemiological evidence suggests a correlation between diabetes and age-related neurodegenerative disorders, including Alzheimer's and Parkinson's diseases. Hyperglycemia causes oxidative stress in vulnerable tissues such as the brain. We recently demonstrated that elevated levels of glucose lead to the death of dopaminergic neurons in culture through oxidative mechanisms. Considering the lack of literature addressing dopaminergic alterations in diabetes with age, the goal of this study was to characterize the state of 2 critical dopaminergic pathways in the nicotinamide-streptozotocin rat model of long-term hyperglycemia, specifically the nigrostriatal motor pathway and the reward-associated mesocorticolimbic pathway. Neuronal and glial alterations were evaluated 3 and 6 months after hyperglycemia induction, demonstrating preferential degeneration of the nigrostriatal pathway complemented by a noticeable astrogliosis and loss of microglial cells throughout aging. Behavioral tests confirmed the existence of motor impairments in hyperglycemic rats that resemble early parkinsonian symptomatology in rats, pensuing from nigrostriatal alterations. These results solidify the relation between hyperglycemia and nigrostriatal dopaminergic neurodegeneration, providing new insight on the higher occurrence of Parkinson's disease in diabetic patients.
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