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Cardiac sympathetic innervation in the MPTP non-human primate model of Parkinson disease

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Abstract

Purpose

Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces degeneration of dopaminergic neurons and reproduces the motor features of Parkinson disease (PD); however, the effect of MPTP on extranigral structures has been poorly studied. The aim of this research was to study the cardiac sympathetic innervation of control and MPTP-treated monkeys in order to describe the influence of MPTP toxicity on cardiac tissue.

Methods

Eight monkeys were included in the study and divided into two groups, four monkeys serving as controls and four forming the MPTP group. Sections from the anterior left ventricle were immunohistochemically examined to characterize the sympathetic fibers of cardiac tissue. The intensity of immunoreactivity in the nerve fibers was quantitatively analyzed using ImageJ software.

Results

As occurs in PD, the sympathetic peripheral nervous system is affected in MPTP-treated monkeys. The percentage of tyrosine hydroxylase immunoreactive fibers in the entire fascicle area was markedly lower in the MPTP group (24.23%) than the control group (35.27%) (p < 0.05), with preservation of neurofilament immunoreactive fibers in the epicardium of MPTP-treated monkeys. Alpha-synuclein deposits were observed in sections of the anterior left ventricle of MPTP-treated monkeys but not in control animals, whereas phosphorylated synuclein aggregates were not observed in either controls or MPTP-treated monkeys.

Conclusion

The peripheral autonomic system can also be affected by neurotoxins that specifically inhibit mitochondrial complex I.

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Funding

This study was partially co-funded by the Instituto de Salud Carlos III through project PI12/01730 from the Spanish Health Research Fund (FIS) and the Association of Friends (ADA) of the University of Navarra (MCA).

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Authors and Affiliations

  1. Neurodegenerative Diseases Group, Neurosciences Division, Biocruces Bizkaia Health Research Institute, Plaza cruces s/n, 48903, Barakaldo, Vizcaya, Spain

    Mar Carmona-Abellan

  2. Neurosciences Division, Center for Applied Medical Research (CIMA), Pamplona, Navarra, Spain

    Ivan Martínez-Valbuena, Irene Marcilla & Maria Rosario Luquin

  3. Idisna HRI, Pamplona, Navarra, Spain

    Ivan Martínez-Valbuena, Irene Marcilla & Maria Rosario Luquin

  4. Neurology Section, Biomedical Center, Granada, Spain

    Carla DiCaudo

  5. Neurology Department, Clinica Universidad de Navarra, Pamplona, Navarra, Spain

    Maria Rosario Luquin

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  1. Mar Carmona-Abellan
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  2. Ivan Martínez-Valbuena
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Correspondence to Mar Carmona-Abellan.

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Carmona-Abellan, M., Martínez-Valbuena, I., DiCaudo, C. et al. Cardiac sympathetic innervation in the MPTP non-human primate model of Parkinson disease. Clin Auton Res 29, 415–425 (2019). https://doi.org/10.1007/s10286-019-00620-0

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  • DOI: https://doi.org/10.1007/s10286-019-00620-0

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