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The Docosanoid Neuroprotectin D1 Induces TH-Positive Neuronal Survival in a Cellular Model of Parkinson’s Disease

Parkinson’s disease (PD) does not manifest clinically until 80 % of striatal dopamine is reduced, thus most neuronal damage takes place before the patient presents clinical symptoms. Therefore, it is important to develop preventive strategies for this disease. In the experimental models of PD, 1-met...

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Autores principales: Calandria, Jorgelina M., Sharp, Michelle W., Bazan, Nicolas G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602058/
https://www.ncbi.nlm.nih.gov/pubmed/26047923
http://dx.doi.org/10.1007/s10571-015-0206-6
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author Calandria, Jorgelina M.
Sharp, Michelle W.
Bazan, Nicolas G.
author_facet Calandria, Jorgelina M.
Sharp, Michelle W.
Bazan, Nicolas G.
author_sort Calandria, Jorgelina M.
collection PubMed
description Parkinson’s disease (PD) does not manifest clinically until 80 % of striatal dopamine is reduced, thus most neuronal damage takes place before the patient presents clinical symptoms. Therefore, it is important to develop preventive strategies for this disease. In the experimental models of PD, 1-methyl-4-phenylpyridinium ion (MPP+) and rotenone induce toxicity in dopaminergic neurons. Neuroprotectin D1 (NPD1) displays neuroprotection in cells undergoing proteotoxic and oxidative stress. In the present report, we established an in vitro model using a primary neuronal culture from mesencephalic embryonic mouse tissue in which 17–20 % of neurons were TH-positive when differentiated in vitro. NPD1 (100 nM) rescued cells from apoptosis induced by MPP+ and rotenone, and the dendritic arbor of surviving neurons was examined using Sholl analysis. Rotenone, as well as MPP+ and its precursor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), severely promoted retraction of dendritic arbor distal segments, thus decreasing the maximum branch order reached. On average, NPD1 counteracted the effects of MPP+ on the dendritic arborization, but failed to do so in the rotenone-treated neurons. However, rotenone did decrease the Sholl intersection number from radii 25 to 125 µm, and NPD1 did restore the pattern to control levels. Similarly, NPD1 partially reverted the dendrite retraction caused by MPP+ and MPTP. These results suggest that the apoptosis occurring in mesencephalic TH-positive neurons is not a direct consequence of mitochondrial dysfunction alone and that NPD1 signaling may be counteracting this damage. These findings lay the groundwork for the use of the in vitro model developed for future studies and for the search of specific molecular events that NPD1 targets to prevent early neurodegeneration in PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10571-015-0206-6) contains supplementary material, which is available to authorized users.
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spelling pubmed-46020582015-10-16 The Docosanoid Neuroprotectin D1 Induces TH-Positive Neuronal Survival in a Cellular Model of Parkinson’s Disease Calandria, Jorgelina M. Sharp, Michelle W. Bazan, Nicolas G. Cell Mol Neurobiol Original Research Parkinson’s disease (PD) does not manifest clinically until 80 % of striatal dopamine is reduced, thus most neuronal damage takes place before the patient presents clinical symptoms. Therefore, it is important to develop preventive strategies for this disease. In the experimental models of PD, 1-methyl-4-phenylpyridinium ion (MPP+) and rotenone induce toxicity in dopaminergic neurons. Neuroprotectin D1 (NPD1) displays neuroprotection in cells undergoing proteotoxic and oxidative stress. In the present report, we established an in vitro model using a primary neuronal culture from mesencephalic embryonic mouse tissue in which 17–20 % of neurons were TH-positive when differentiated in vitro. NPD1 (100 nM) rescued cells from apoptosis induced by MPP+ and rotenone, and the dendritic arbor of surviving neurons was examined using Sholl analysis. Rotenone, as well as MPP+ and its precursor 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), severely promoted retraction of dendritic arbor distal segments, thus decreasing the maximum branch order reached. On average, NPD1 counteracted the effects of MPP+ on the dendritic arborization, but failed to do so in the rotenone-treated neurons. However, rotenone did decrease the Sholl intersection number from radii 25 to 125 µm, and NPD1 did restore the pattern to control levels. Similarly, NPD1 partially reverted the dendrite retraction caused by MPP+ and MPTP. These results suggest that the apoptosis occurring in mesencephalic TH-positive neurons is not a direct consequence of mitochondrial dysfunction alone and that NPD1 signaling may be counteracting this damage. These findings lay the groundwork for the use of the in vitro model developed for future studies and for the search of specific molecular events that NPD1 targets to prevent early neurodegeneration in PD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s10571-015-0206-6) contains supplementary material, which is available to authorized users. Springer US 2015-06-06 2015 /pmc/articles/PMC4602058/ /pubmed/26047923 http://dx.doi.org/10.1007/s10571-015-0206-6 Text en © The Author(s) 2015 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided 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.
spellingShingle Original Research
Calandria, Jorgelina M.
Sharp, Michelle W.
Bazan, Nicolas G.
The Docosanoid Neuroprotectin D1 Induces TH-Positive Neuronal Survival in a Cellular Model of Parkinson’s Disease
title The Docosanoid Neuroprotectin D1 Induces TH-Positive Neuronal Survival in a Cellular Model of Parkinson’s Disease
title_full The Docosanoid Neuroprotectin D1 Induces TH-Positive Neuronal Survival in a Cellular Model of Parkinson’s Disease
title_fullStr The Docosanoid Neuroprotectin D1 Induces TH-Positive Neuronal Survival in a Cellular Model of Parkinson’s Disease
title_full_unstemmed The Docosanoid Neuroprotectin D1 Induces TH-Positive Neuronal Survival in a Cellular Model of Parkinson’s Disease
title_short The Docosanoid Neuroprotectin D1 Induces TH-Positive Neuronal Survival in a Cellular Model of Parkinson’s Disease
title_sort docosanoid neuroprotectin d1 induces th-positive neuronal survival in a cellular model of parkinson’s disease
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4602058/
https://www.ncbi.nlm.nih.gov/pubmed/26047923
http://dx.doi.org/10.1007/s10571-015-0206-6
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