3 research outputs found
Cambios en la inervación de dopamina talámica en un modelo de enfermedad de Parkinson progresiva en monos
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.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