单胺类
多巴胺
纹状体
终纹
运动障碍
神经科学
海马体
扁桃形结构
帕金森病
内科学
内分泌学
化学
生物
医学
疾病
血清素
受体
作者
Elva Fridjonsdottir,Mohammadreza Shariatgorji,Anna Nilsson,Theodosia Vallianatou,Luke R. Odell,Luke S. Schembri,Per Svenningsson,Pierre‐Olivier Fernagut,Alan R. Crossman,Erwan Bézard,Per E. Andrén
出处
期刊:Science Advances
[American Association for the Advancement of Science (AAAS)]
日期:2021-01-08
卷期号:7 (2)
被引量:29
标识
DOI:10.1126/sciadv.abe5948
摘要
l-DOPA treatment for Parkinson's disease frequently leads to dyskinesias, the pathophysiology of which is poorly understood. We used MALDI-MSI to map the distribution of l-DOPA and monoaminergic pathways in brains of dyskinetic and nondyskinetic primates. We report elevated levels of l-DOPA, and its metabolite 3-O-methyldopa, in all measured brain regions of dyskinetic animals and increases in dopamine and metabolites in all regions analyzed except the striatum. In dyskinesia, dopamine levels correlated well with l-DOPA levels in extrastriatal regions, such as hippocampus, amygdala, bed nucleus of the stria terminalis, and cortical areas, but not in the striatum. Our results demonstrate that l-DOPA-induced dyskinesia is linked to a dysregulation of l-DOPA metabolism throughout the brain. The inability of extrastriatal brain areas to regulate the formation of dopamine during l-DOPA treatment introduces the potential of dopamine or even l-DOPA itself to modulate neuronal signaling widely across the brain, resulting in unwanted side effects.
科研通智能强力驱动
Strongly Powered by AbleSci AI