Cargando…

Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis

Central Nervous System inflammation has been implicated in neurodegenerative disorders including Parkinson’s disease (Ransohoff, Science 353: 777–783, 2016; Kannarkat et al. J. Parkinsons Dis. 3: 493–514, 2013). Here, we examined if the H1N1 influenza virus (Studahl et al. Drugs 73: 131–158, 2013) c...

Descripción completa

Detalles Bibliográficos
Autores principales: Sadasivan, Shankar, Sharp, Bridgett, Schultz-Cherry, Stacey, Smeyne, Richard Jay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460228/
https://www.ncbi.nlm.nih.gov/pubmed/28649618
http://dx.doi.org/10.1038/s41531-017-0019-z
_version_ 1783242122477961216
author Sadasivan, Shankar
Sharp, Bridgett
Schultz-Cherry, Stacey
Smeyne, Richard Jay
author_facet Sadasivan, Shankar
Sharp, Bridgett
Schultz-Cherry, Stacey
Smeyne, Richard Jay
author_sort Sadasivan, Shankar
collection PubMed
description Central Nervous System inflammation has been implicated in neurodegenerative disorders including Parkinson’s disease (Ransohoff, Science 353: 777–783, 2016; Kannarkat et al. J. Parkinsons Dis. 3: 493–514, 2013). Here, we examined if the H1N1 influenza virus (Studahl et al. Drugs 73: 131–158, 2013) could synergize with the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (Jackson-Lewis et al. in Mark LeDoux (ed) Movement Disorders: Genetics and Models: 287–306, Elsevier, 2015) to induce a greater microglial activation and loss of substantia nigra pars compacta dopaminergic neurons than either insult alone. H1N1-infected animals administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exhibit a 20% greater loss of substantia nigra pars compacta dopaminergic neurons than occurs from the additive effects of H1N1 or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine alone (p < 0.001). No synergistic effects were found in microglial activation. The synergistic dopaminergic neuron loss is eliminated by influenza vaccination or treatment with oseltamivir carboxylate. This work shows that multiple insults can induce synergistic effects; and even these small changes can be significant as it might allow one to cross a phenotypic disease threshold that would not occur from individual non-interacting exposures. Our observations also have important implications for public health, providing impetus for influenza vaccination or prompt treatment with anti-viral medications upon influenza diagnosis.
format Online
Article
Text
id pubmed-5460228
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-54602282017-06-23 Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis Sadasivan, Shankar Sharp, Bridgett Schultz-Cherry, Stacey Smeyne, Richard Jay NPJ Parkinsons Dis Brief Communication Central Nervous System inflammation has been implicated in neurodegenerative disorders including Parkinson’s disease (Ransohoff, Science 353: 777–783, 2016; Kannarkat et al. J. Parkinsons Dis. 3: 493–514, 2013). Here, we examined if the H1N1 influenza virus (Studahl et al. Drugs 73: 131–158, 2013) could synergize with the parkinsonian toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (Jackson-Lewis et al. in Mark LeDoux (ed) Movement Disorders: Genetics and Models: 287–306, Elsevier, 2015) to induce a greater microglial activation and loss of substantia nigra pars compacta dopaminergic neurons than either insult alone. H1N1-infected animals administered 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine exhibit a 20% greater loss of substantia nigra pars compacta dopaminergic neurons than occurs from the additive effects of H1N1 or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine alone (p < 0.001). No synergistic effects were found in microglial activation. The synergistic dopaminergic neuron loss is eliminated by influenza vaccination or treatment with oseltamivir carboxylate. This work shows that multiple insults can induce synergistic effects; and even these small changes can be significant as it might allow one to cross a phenotypic disease threshold that would not occur from individual non-interacting exposures. Our observations also have important implications for public health, providing impetus for influenza vaccination or prompt treatment with anti-viral medications upon influenza diagnosis. Nature Publishing Group UK 2017-05-23 /pmc/articles/PMC5460228/ /pubmed/28649618 http://dx.doi.org/10.1038/s41531-017-0019-z Text en © The Author(s) 2017 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Brief Communication
Sadasivan, Shankar
Sharp, Bridgett
Schultz-Cherry, Stacey
Smeyne, Richard Jay
Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis
title Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis
title_full Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis
title_fullStr Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis
title_full_unstemmed Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis
title_short Synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis
title_sort synergistic effects of influenza and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (mptp) can be eliminated by the use of influenza therapeutics: experimental evidence for the multi-hit hypothesis
topic Brief Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5460228/
https://www.ncbi.nlm.nih.gov/pubmed/28649618
http://dx.doi.org/10.1038/s41531-017-0019-z
work_keys_str_mv AT sadasivanshankar synergisticeffectsofinfluenzaand1methyl4phenyl1236tetrahydropyridinemptpcanbeeliminatedbytheuseofinfluenzatherapeuticsexperimentalevidenceforthemultihithypothesis
AT sharpbridgett synergisticeffectsofinfluenzaand1methyl4phenyl1236tetrahydropyridinemptpcanbeeliminatedbytheuseofinfluenzatherapeuticsexperimentalevidenceforthemultihithypothesis
AT schultzcherrystacey synergisticeffectsofinfluenzaand1methyl4phenyl1236tetrahydropyridinemptpcanbeeliminatedbytheuseofinfluenzatherapeuticsexperimentalevidenceforthemultihithypothesis
AT smeynerichardjay synergisticeffectsofinfluenzaand1methyl4phenyl1236tetrahydropyridinemptpcanbeeliminatedbytheuseofinfluenzatherapeuticsexperimentalevidenceforthemultihithypothesis