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Cited by 37Parkinson's Disease Mechanisms and TreatmentsNeurological disorders and treatmentsNeurotransmitter Receptor Influence on Behavior

Reduced noradrenergic innervation of ventral midbrain dopaminergic cell groups and the subthalamic nucleus in MPTP-treated parkinsonian monkeys

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Masilamoni, Gunasingh Jeyaraj, Groover, Olivia, Smith, Yoland·2017·Neurobiology of Disease
DOI 10.1016/j.nbd.2016.12.025PMC PMC5511687
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Abstract

There is anatomical and functional evidence that ventral midbrain dopaminergic (DA) cell groups and the subthalamic nucleus (STN) receive noradrenergic innervation in rodents, but much less is known about these interactions in primates. Degeneration of NE neurons in the locus coeruleus (LC) and related brainstem NE cell groups is a well-established pathological feature of Parkinson's disease (PD), but the development of such pathology in animal models of PD has been inconsistent across species and laboratories. We recently demonstrated 30-40% neuronal loss in the LC, A5 and A6 NE cell groups of rhesus monkeys rendered parkinsonian by chronic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). In this study, we used dopamine-beta-hydroxylase (DβH) immunocytochemistry to assess the impact of this neuronal loss on the number of NE terminal-like varicosities in the substantia nigra pars compacta (SNC), ventral tegmental area (VTA), retrorubral field (RRF) and STN of MPTP-treated parkinsonian monkeys. Our findings reveal that the NE innervation of the ventral midbrain and STN of normal monkeys is heterogeneously distributed being far more extensive in the VTA, RRF and dorsal tier of the SNC than in the ventral SNC and STN. In parkinsonian monkeys, all regions underwent a significant (~50-70%) decrease in NE innervation. At the electron microscopic level, some DβH-positive terminals formed asymmetric axo-dendritic synapses in VTA and STN. These findings demonstrate that the VTA, RRF and SNCd are the main ventral midbrain targets of ascending NE inputs, and that these connections undergo a major break-down in chronically MPTP-treated parkinsonian monkeys. This severe degeneration of the ascending NE system may contribute to the pathophysiology of ventral midbrain and STN neurons in PD.

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  • Light hair color and red hair MC1R alleles are risk factors for both melanoma and Parkinson's disease, and Parkinson's disease patients have a 7-fold elevated melanoma risk.

    “Light hair color and the red hair alleles of the MC1R gene are risk factors for both melanoma and PD, while PD patients have a 7-fold elevated risk for melanoma (239, 240);”

    From Chemiexcitation: Mammalian Photochemistry in the Dark<sup>†</sup> (2023) · cites this paper as [239]

    The Results (§3.1; page unavailable) concern dopamine and noradrenergic neuron loss in MPTP-treated monkeys. Searches of our copy for MC1R, red hair, melanoma, and a 7-fold melanoma risk found no passage addressing either part of the claim. (LLM, conf=0.76)

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  1. Gaspar P 1994 Anatomy of the Noradrenergic Pathways in the Primate Brain Alteration in Parkinson’s Disease CRC Press Boca Raton 73 88

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Authors
Masilamoni, G. J., Groover, O., & Smith, Y.
Affiliations
Emory University (US)
Corresponding author
Smith, Yoland
ORCID
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2017-04
Volume
100
Pages
9-18
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2016.12.025
PMC
PMC5511687
OpenAlex
W2561957799
Cited by
37
References
96
Citations by year
2026: 4 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 6 · 2021: 3 · 2020: 5 · 2019: 2 · 2018: 5 · 2017: 4
FWCI
2.76
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Neurobiology of Disease (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • NIH/ORIP (P51-OD011132)
  • National Parkinson Foundation
  • NIH/NINDS (P50-NS071669)
Topics
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Neurology › Neurological disorders and treatments
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Keywords
noradrenergic innervation, ventral midbrain, subthalamic nucleus, Parkinson's disease, MPTP, locus coeruleus, ventral tegmental area, substantia nigra pars compacta, retrorubral field, dopamine beta-hydroxylase, axodendritic synapses, rhesus monkeys, neurodegeneration
MeSH terms
Animals, Dendrites, Disease Models, Animal, Macaca mulatta, Male, Mesencephalon, Substantia Nigra, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Ventral Tegmental Area, MPTP Poisoning, Subthalamic Nucleus, Dopaminergic Neurons

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