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Astrocytes and retrograde degeneration of nigrostriatal dopaminergic neurons in Parkinson’s disease:removing axonal debris

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Translational Neurodegeneration 2021年第4期10卷 554-572页

作者： Ingrid Morales Ricardo Puertas-Avendaño Alberto Sanchez adrian perez-barreto Clara Rodriguez-Sabate Manuel Rodriguez Laboratory of Neurobiology and Experimental Neurology Department of Basic Medical SciencesFaculty of MedicineLa Laguna UniversityLa LagunaTenerifeCanary IslandsSpain Center for Networked Biomedical Research on Neurodegenerative Diseases(CIBERNED) MadridSpain

Objective:The dopaminergic nigrostriatal neurons(DA cells)in healthy people present a slow degeneration with aging,which produces cellular debris throughout *** 2%-5%of people present rapid cell degeneration of more than 50%of DA cells,which produces Parkinson's disease(PD).Neuroinflammation accelerates the cell degeneration and may be critical for the transition between the slow physiological and the rapid pathological degeneration of DA cells,particularly when it activates microglial cells of the medial forebrain bundle near dopaminergic *** synaptic debris produced by DA cell degeneration may trigger the parkinsonian neuroinflammation,this study investigated the removal of axonal debris produced by retrograde degeneration of DA cells,paying particular attention to the relative roles of astrocytes and ***:Rats and mice were injected in the lateral ventricles with 6-hydroxydopamine,inducing a degeneration of dopaminergic synapses in the striatum which was not accompanied by non-selective tissue damage,microgliosis or *** possible retrograde degeneration of dopaminergic axons,and the production and metabolization of DA-cell debris were studied with immunohistochemical methods and analyzed in confocal and electron microscopy ***:The selective degeneration of dopaminergic synapses in the striatum was followed by a retrograde degeneration of dopaminergic axons whose debris was found within spheroids of the medial forebrain *** spheroids retained mitochondria and most(e.g.,tyrosine hydroxylase,the dopamine transporter protein,and amyloid precursor protein)but not all(e.g.,α-synuclein)proteins of the degenerating dopaminergic *** showed initial(autophagosomes)but not late(lysosomes)components of autophagy(incomplete autophagy).These spheroids were penetrated by astrocytic processes of the medial forebrain bundle,which provided the lysosomes needed to continue the degradation of dopaminergic debri

关键词： Astrocyte Phagocytosis Parkinson's disease Dying-back degeneration Medial forebrain bundle Spheroid

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