The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease
Biondetti, Emma (Team "Movement Investigations and Therapeutics")
Santin, Mathieu D. (Centre de NeuroImagerie de Recherche)
Valabrègue, Romain (Centre de NeuroImagerie de Recherche)
Mangone, Graziella (Assistance Publique Hôpitaux de Paris)
Gaurav, Rahul (Team "Movement Investigations and Therapeutics")
Pyatigorskaya, Nadya (Assistance Publique Hôpitaux de Paris)
Hutchison, Matthew (Biogen (Estats Units d'Amèrica))
Yahia-Cherif, Lydia (Centre de NeuroImagerie de Recherche)
Villain, Nicolas (Assistance Publique Hôpitaux de Paris)
Habert, Marie-Odile (Sorbonne Université)
Arnulf, Isabelle (Assistance Publique Hôpitaux de Paris)
Leu-Semenescu, Smaranda (Hôpital Pitié-Salpêtrière)
Dodet, Pauline (Assistance Publique Hôpitaux de Paris)
Vila Bover, Miquel (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Corvol, Jean-Christophe (Assistance Publique Hôpitaux de Paris)
Vidailhet, Marie (Assistance Publique Hôpitaux de Paris)
Lehéricy, Stéphane (Assistance Publique Hôpitaux de Paris)
Universitat Autònoma de Barcelona

Data:	2021
Resum:	In Parkinson's disease, there is a progressive reduction in striatal dopaminergic function, and loss of neuromelanin-containing dopaminergic neurons and increased iron deposition in the substantia nigra. We tested the hypothesis of a relationship between impairment of the dopaminergic system and changes in the iron metabolism. Based on imaging data of patients with prodromal and early clinical Parkinson's disease, we assessed the spatiotemporal ordering of such changes and relationships in the sensorimotor, associative and limbic territories of the nigrostriatal system. Patients with Parkinson's disease (disease duration < 4 years) or idiopathic REM sleep behaviour disorder (a prodromal form of Parkinson's disease) and healthy controls underwent longitudinal examination (baseline and 2-year follow-up). Neuromelanin and iron sensitive MRI and dopamine transporter single-photon emission tomography were performed to assess nigrostriatal levels of neuromelanin, iron, and dopamine. For all three functional territories of the nigrostriatal system, in the clinically most and least affected hemispheres separately, the following was performed: cross-sectional and longitudinal intergroup difference analysis of striatal dopamine and iron, and nigral neuromelanin and iron; in Parkinson's disease patients, exponential fitting analysis to assess the duration of the prodromal phase and the temporal ordering of changes in dopamine, neuromelanin or iron relative to controls; and voxel-wise correlation analysis to investigate concomitant spatial changes in dopamine-iron, dopamine-neuromelanin and neuromelanin-iron in the substantia nigra pars compacta. The temporal ordering of dopaminergic changes followed the known spatial pattern of progression involving first the sensorimotor, then the associative and limbic striatal and nigral regions. Striatal dopaminergic denervation occurred first followed by abnormal iron metabolism and finally neuromelanin changes in the substantia nigra pars compacta, which followed the same spatial and temporal gradient observed in the striatum but shifted in time. In conclusion, dopaminergic striatal dysfunction and cell loss in the substantia nigra pars compacta are interrelated with increased nigral iron content. Using multi-modal imaging (MRI and SPECT) in patients with prodromal and early clinical Parkinson's disease, Biondetti et al. reveal dopaminergic changes, abnormal iron metabolism and neuromelanin changes first in the sensorimotor, then the associative and finally the limbic regions of the nigrostriatal system.
Nota:	Altres ajuts: Fondation Thérèse and René Planiol: ANR-11-INBS-0006
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, sempre que no sigui amb finalitats comercials, i sempre que es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Parkinson's disease ; Neuromelanin ; Iron ; Dopamine transporter ; Imaging
Publicat a:	Brain, Vol. 144 (may 2021) , p. 3114-3125, ISSN 1460-2156

DOI: 10.1093/brain/awab191
PMID: 33978742

12 p, 909.2 KB

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