Changes in thalamic dopamine innervation in a progressive Parkinson’s disease model in monkeys
Title (trans.)
Cambios en la inervación de dopamina talámica en un modelo de enfermedad de Parkinson progresiva en monosEntity
UAM. Departamento de Anatomía, Histología y NeurocienciaPublisher
Wiley Periodicals, Inc.; International Parkinson y la Sociedad de Trastornos del MovimientoDate
2019-12-04Citation
10.1002/mds.27921
Movement Disorders 35.3 (2020): 419-430
ISSN
0885-3185DOI
10.1002/mds.27921Funded by
Chair in Neuroscience UAM-Fundación Tatiana Pérez de Guzmán el Bueno directed by C.C. J.A.O. and J.B. are currently funded by MINECO/AEI/FEDER-UE (SAF2015-67239-P), grant S2017/BMD-3700 (NEUROMETAB-CM) from Comunidad de Madrid cofinanced with Structural Funds from the European Union, La Caixa Foundation, Fundación BBVA, and Fundación Tatiana Pérez de Guzmán el Bueno.Project
Gobierno de España. SAF2015-67239-P; Comunidad de Madrid. S2017/BMD-3700 /NEUROMETABEditor's Version
https://doi.org/10.1002/mds.27921Subjects
Dopamine; Macaque monkey; MPTP; Parkinson’s disease; Thalamus; MedicinaRights
© 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder SocietyAbstract
Background: Dopamine loss beyond the
mesostriatal system might be relevant in pathogenic
mechanisms and some clinical manifestations in PD. The
primate thalamus is densely and heterogeneously innervated
with dopaminergic axons, most of which express
the dopamine transporter, as does the nigrostriatal system.
We hypothesized that dopamine depletion may be
present in the thalamus of the parkinsonian brain and set
out to ascertain possible regional differences.
Methods: The toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine
was administered to adult macaque monkeys
using a slow intoxication protocol. The treated macaques
were classified into 2 groups according to their motor status:
nonsymptomatic and parkinsonian. Dopamine innervation
was studied with immunohistochemistry for the
dopamine transporter. Topographic maps of the dopamine
transporter-immunoreactive axon distribution were generated
and the total length and length density of these axons
stereologically estimated using a 3-dimensional fractionator.
Results: Parkinsonian macaques exhibited lower dopamine
transporter-immunoreactive axon length density
than controls in mediodorsal and centromedianparafascicular
nuclei. Dopamine denervation in the
mediodorsal nucleus was already noticeable in nonsymptomatic
macaques and was even greater in parkinsonian
macaques. Reticular nucleus dopamine
transporter-immunoreactive axon length density presented
an inverse pattern, increasing progressively to the
maximum density seen in parkinsonian macaques. No
changes were observed in ventral thalamic nuclei.
Dopamine transporter-immunoreactive axon maps
supported the quantitative findings.
Conclusions: Changes in the dopamine innervation of
various thalamic nuclei are heterogeneous and start in the
premotor parkinsonian stage. These changes may be
involved in some poorly understood nonmotor manifestations
of PD.
Files in this item
Google Scholar:Monje, Mariana H.G.
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Blesa, Javier
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García-Cabezas, Miguel Ángel
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Obeso, José A.
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Cavada Martínez, Carmen
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