The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease

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 an...

Descripción completa

Detalles Bibliográficos
Autores: Biondetti, Emma|||0000-0001-6727-0935, Santin, Mathieu D., Valabrègue, Romain, Mangone, Graziella, Gaurav, Rahul|||0000-0001-9983-5873, Pyatigorskaya, Nadya|||0000-0002-2070-1299, Hutchison, Matthew, Yahia-Cherif, Lydia, Villain, Nicolas, Habert, Marie-Odile, Arnulf, Isabelle|||0000-0002-2240-2516, Leu-Semenescu, Smaranda|||0000-0001-9556-4527, Dodet, Pauline, Vila Bover, Miquel|||0000-0002-1352-989X, Corvol, Jean-Christophe|||0000-0001-7325-0199, Vidailhet, Marie, Lehéricy, Stéphane
Tipo de recurso: artículo
Fecha de publicación:2021
País:España
Institución:Universitat Autònoma de Barcelona
Repositorio:Dipòsit Digital de Documents de la UAB
Idioma:inglés
OAI Identifier:oai:ddd.uab.cat:255563
Acceso en línea:https://ddd.uab.cat/record/255563
https://dx.doi.org/urn:doi:10.1093/brain/awab191
Access Level:acceso abierto
Palabra clave:Parkinson's disease
Neuromelanin
Iron
Dopamine transporter
Imaging
id ES_afaa438b0439f9ae9a3c4e002eec63cf
oai_identifier_str oai:ddd.uab.cat:255563
network_acronym_str ES
network_name_str España
repository_id_str
spelling The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's diseaseBiondetti, Emma|||0000-0001-6727-0935Santin, Mathieu D.Valabrègue, RomainMangone, GraziellaGaurav, Rahul|||0000-0001-9983-5873Pyatigorskaya, Nadya|||0000-0002-2070-1299Hutchison, MatthewYahia-Cherif, LydiaVillain, NicolasHabert, Marie-OdileArnulf, Isabelle|||0000-0002-2240-2516Leu-Semenescu, Smaranda|||0000-0001-9556-4527Dodet, PaulineVila Bover, Miquel|||0000-0002-1352-989XCorvol, Jean-Christophe|||0000-0001-7325-0199Vidailhet, MarieLehéricy, StéphaneParkinson's diseaseNeuromelaninIronDopamine transporterImagingIn 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 systemUniversitat Autònoma de Barcelona 22021-01-0120212021-01-01Articlehttp://purl.org/coar/resource_type/c_6501VoRhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/articleapplication/pdfhttps://ddd.uab.cat/record/255563https://dx.doi.org/urn:doi:10.1093/brain/awab191reponame:Dipòsit Digital de Documents de la UABinstname:Universitat Autònoma de BarcelonaInglésengopen accesshttp://purl.org/coar/access_right/c_abf2Aquest 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.https://creativecommons.org/licenses/by-nc/4.0/info:eu-repo/semantics/openAccessoai:ddd.uab.cat:2555632026-06-06T12:50:31Z
dc.title.none.fl_str_mv The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease
title The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease
spellingShingle The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease
Biondetti, Emma|||0000-0001-6727-0935
Parkinson's disease
Neuromelanin
Iron
Dopamine transporter
Imaging
title_short The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease
title_full The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease
title_fullStr The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease
title_full_unstemmed The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease
title_sort The spatiotemporal changes in dopamine, neuromelanin and iron characterizing Parkinson's disease
dc.creator.none.fl_str_mv Biondetti, Emma|||0000-0001-6727-0935
Santin, Mathieu D.
Valabrègue, Romain
Mangone, Graziella
Gaurav, Rahul|||0000-0001-9983-5873
Pyatigorskaya, Nadya|||0000-0002-2070-1299
Hutchison, Matthew
Yahia-Cherif, Lydia
Villain, Nicolas
Habert, Marie-Odile
Arnulf, Isabelle|||0000-0002-2240-2516
Leu-Semenescu, Smaranda|||0000-0001-9556-4527
Dodet, Pauline
Vila Bover, Miquel|||0000-0002-1352-989X
Corvol, Jean-Christophe|||0000-0001-7325-0199
Vidailhet, Marie
Lehéricy, Stéphane
author Biondetti, Emma|||0000-0001-6727-0935
author_facet Biondetti, Emma|||0000-0001-6727-0935
Santin, Mathieu D.
Valabrègue, Romain
Mangone, Graziella
Gaurav, Rahul|||0000-0001-9983-5873
Pyatigorskaya, Nadya|||0000-0002-2070-1299
Hutchison, Matthew
Yahia-Cherif, Lydia
Villain, Nicolas
Habert, Marie-Odile
Arnulf, Isabelle|||0000-0002-2240-2516
Leu-Semenescu, Smaranda|||0000-0001-9556-4527
Dodet, Pauline
Vila Bover, Miquel|||0000-0002-1352-989X
Corvol, Jean-Christophe|||0000-0001-7325-0199
Vidailhet, Marie
Lehéricy, Stéphane
author_role author
author2 Santin, Mathieu D.
Valabrègue, Romain
Mangone, Graziella
Gaurav, Rahul|||0000-0001-9983-5873
Pyatigorskaya, Nadya|||0000-0002-2070-1299
Hutchison, Matthew
Yahia-Cherif, Lydia
Villain, Nicolas
Habert, Marie-Odile
Arnulf, Isabelle|||0000-0002-2240-2516
Leu-Semenescu, Smaranda|||0000-0001-9556-4527
Dodet, Pauline
Vila Bover, Miquel|||0000-0002-1352-989X
Corvol, Jean-Christophe|||0000-0001-7325-0199
Vidailhet, Marie
Lehéricy, Stéphane
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Universitat Autònoma de Barcelona
dc.subject.none.fl_str_mv Parkinson's disease
Neuromelanin
Iron
Dopamine transporter
Imaging
topic Parkinson's disease
Neuromelanin
Iron
Dopamine transporter
Imaging
description 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
publishDate 2021
dc.date.none.fl_str_mv 2
2021-01-01
2021
2021-01-01
dc.type.none.fl_str_mv Article
http://purl.org/coar/resource_type/c_6501
VoR
http://purl.org/coar/version/c_970fb48d4fbd8a85
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://ddd.uab.cat/record/255563
https://dx.doi.org/urn:doi:10.1093/brain/awab191
url https://ddd.uab.cat/record/255563
https://dx.doi.org/urn:doi:10.1093/brain/awab191
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
https://creativecommons.org/licenses/by-nc/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.source.none.fl_str_mv reponame:Dipòsit Digital de Documents de la UAB
instname:Universitat Autònoma de Barcelona
instname_str Universitat Autònoma de Barcelona
reponame_str Dipòsit Digital de Documents de la UAB
collection Dipòsit Digital de Documents de la UAB
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869416703815843840
score 15,300724