Axonal damage and loss of connectivity in nigrostriatal and mesolimbic dopamine pathways in early Parkinson's disease
| Autor: | Valentina Garibotto, Luigi Gianolli, Silvia Paola Caminiti, Damiano Baroncini, Angelo Antonini, Luca Presotto, Rosa Maria Moresco, Maria Antonietta Volontè, Daniela Perani |
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| Přispěvatelé: | Caminiti, S, Presotto, L, Baroncini, D, Garibotto, V, Moresco, R, Gianolli, L, Volonté, M, Antonini, A, Perani, D, Caminiti, S. P., Presotto, L., Baroncini, D., Garibotto, V., Moresco, R. M., Gianolli, L., Volontã©, M. A., Antonini, A., Perani, DANIELA FELICITA L. |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male ventral tegmental area cAS Radiology Nuclear Medicine and Imaging Parkinson's disease Dopamine Axonal damage Nigrostriatal pathway VST ventral striatum lcsh:RC346-429 MED/50 - SCIENZE TECNICHE MEDICHE APPLICATE Substantia Nigra/diagnostic imaging ventral striatum VTA Dopamine Plasma Membrane Transport Protein 0302 clinical medicine Retrospective Studie Limbic System MED/36 - DIAGNOSTICA PER IMMAGINI E RADIOTERAPIA biology Putamen Dopaminergic Parkinson Disease Regular Article Brain Injuries/diagnostic imaging/etiology/pathology Middle Aged cAS clinical asymmetry Ventral tegmental area Substantia Nigra medicine.anatomical_structure Molecular connectivity Neurology Axons/metabolism/pathology Dopamine transporter lcsh:R858-859.7 SN substantia nigra Female Psychology dorsal caudate DPU Dopamine Plasma Membrane Transport Proteins/metabolism medicine.drug Human AI asymmetry index Positron emission tomography Cognitive Neuroscience clinical asymmetry Substantia nigra DCA dorsal caudate lcsh:Computer applications to medicine. Medical informatics VTA ventral tegmental area ddc:616.0757 Axon Parkinson Disease/complications/diagnostic imaging 03 medical and health sciences Brain Injurie Image Interpretation Computer-Assisted dorsal putamen SN medicine Humans substantia nigra SUVr lcsh:Neurology. Diseases of the nervous system SUVr standardized uptake value ratio Aged Retrospective Studies Dopamine Plasma Membrane Transport Proteins medicine.disease Axons Corpus Striatum Dopamine/metabolism asymmetry index DCA 030104 developmental biology nervous system Corpus Striatum/diagnostic imaging Brain Injuries Positron-Emission Tomography biology.protein Limbic System/diagnostic imaging Neurology (clinical) standardized uptake value ratio VST Neuroscience DPU dorsal putamen 030217 neurology & neurosurgery |
| Zdroj: | NeuroImage: Clinical 14 (2017): 734–740. doi:10.1016/j.nicl.2017.03.011 info:cnr-pdr/source/autori:Caminiti, Silvia Paola; Presotto, Luca; Baroncini, Damiano; Garibotto, Valentina; Moresco, Rosa Maria; Gianolli, Luigi; Volonte, Maria Antonietta; Antonini, Angelo; Perani, Daniela/titolo:Axonal damage and loss of connectivity in nigrostriatal and mesolimbic dopamine pathways in early Parkinson's disease./doi:10.1016%2Fj.nicl.2017.03.011/rivista:NeuroImage: Clinical/anno:2017/pagina_da:734/pagina_a:740/intervallo_pagine:734–740/volume:14 NeuroImage: Clinical, Vol. 14 (2017) pp. 734-740 NeuroImage : Clinical NeuroImage: Clinical, Vol 14, Iss C, Pp 734-740 (2017) |
| ISSN: | 2213-1582 |
| DOI: | 10.1016/j.nicl.2017.03.011 |
| Popis: | A progressive loss of dopamine neurons in the substantia nigra (SN) is considered the main feature of idiopathic Parkinson's disease (PD). Recent neuropathological evidence however suggests that the axons of the nigrostriatal dopaminergic system are the earliest target of α-synuclein accumulation in PD, thus the principal site for vulnerability. Whether this applies to in vivo PD, and also to the mesolimbic system has not been investigated yet. We used [11C]FeCIT PET to measure presynaptic dopamine transporter (DAT) activity in both nigrostriatal and mesolimbic systems, in 36 early PD patients (mean disease duration in months ± SD 21.8 ± 10.7) and 14 healthy controls similar for age. We also performed anatomically-driven partial correlation analysis to evaluate possible changes in the connectivity within both the dopamine networks at an early clinical phase. In the nigrostriatal system, we found a severe DAT reduction in the afferents to the dorsal putamen (DPU) (η2 = 0.84), whereas the SN was the less affected region (η2 = 0.31). DAT activity in the ventral tegmental area (VTA) and the ventral striatum (VST) were also reduced in the patient group, but to a lesser degree (VST η2 = 0.71 and VTA η2 = 0.31). In the PD patients compared to the controls, there was a marked decrease in dopamine network connectivity between SN and DPU nodes, supporting the significant derangement in the nigrostriatal pathway. These results suggest that neurodegeneration in the dopamine pathways is initially more prominent in the afferent axons and more severe in the nigrostriatal system. Considering PD as a disconnection syndrome starting from the axons, it would justify neuroprotective interventions even if patients have already manifested clinical symptoms. Highlights • In vivo study of mesolimbic and nigrostriatal dopamine systems in early iPD • Evidence for a severe axonal damage with relative sparing of SN • Evidence for a moderate damage of the mesolimbic pathway in early iPD • Significant reduction of molecular connectivity between nigrostriatal nodes • Justification for neuroprotective interventions in early-iPD phase |
| Databáze: | OpenAIRE |
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