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Neural ablation of the PARK10 candidate Plpp3 leads to dopaminergic transmission deficits without neurodegeneration
Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder, characterised by the progressive loss of midbrain dopaminergic neurons and a variety of motor symptoms. The gene coding for the phospholipid phosphatase 3, PLPP3 (formerly PPAP2B or LPP3), maps within the PARK10 locus, a region...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827058/ https://www.ncbi.nlm.nih.gov/pubmed/27063549 http://dx.doi.org/10.1038/srep24028 |
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author | Gómez-López, Sandra Martínez-Silva, Ana Valeria Montiel, Teresa Osorio-Gómez, Daniel Bermúdez-Rattoni, Federico Massieu, Lourdes Escalante-Alcalde, Diana |
author_facet | Gómez-López, Sandra Martínez-Silva, Ana Valeria Montiel, Teresa Osorio-Gómez, Daniel Bermúdez-Rattoni, Federico Massieu, Lourdes Escalante-Alcalde, Diana |
author_sort | Gómez-López, Sandra |
collection | PubMed |
description | Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder, characterised by the progressive loss of midbrain dopaminergic neurons and a variety of motor symptoms. The gene coding for the phospholipid phosphatase 3, PLPP3 (formerly PPAP2B or LPP3), maps within the PARK10 locus, a region that has been linked with increased risk to late-onset PD. PLPP3 modulates the levels of a range of bioactive lipids controlling fundamental cellular processes within the central nervous system. Here we show that PLPP3 is enriched in astroglial cells of the adult murine ventral midbrain. Conditional inactivation of Plpp3 using a Nestin::Cre driver results in reduced mesencephalic levels of sphingosine-1-phosphate receptor 1 (S1P(1)), a well-known mediator of pro-survival responses. Yet, adult PLPP3-deficient mice exhibited no alterations in the number of dopaminergic neurons or in the basal levels of striatal extracellular dopamine (DA). Potassium-evoked DA overflow in the striatum, however, was significantly decreased in mutant mice. Locomotor evaluation revealed that, although PLPP3-deficient mice exhibit motor impairment, this is not progressive or responsive to acute L-DOPA therapy. These findings suggest that disruption of Plpp3 during early neural development leads to dopaminergic transmission deficits in the absence of nigrostriatal degeneration, and without causing an age-related locomotor decline consistent with PD. |
format | Online Article Text |
id | pubmed-4827058 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-48270582016-04-19 Neural ablation of the PARK10 candidate Plpp3 leads to dopaminergic transmission deficits without neurodegeneration Gómez-López, Sandra Martínez-Silva, Ana Valeria Montiel, Teresa Osorio-Gómez, Daniel Bermúdez-Rattoni, Federico Massieu, Lourdes Escalante-Alcalde, Diana Sci Rep Article Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder, characterised by the progressive loss of midbrain dopaminergic neurons and a variety of motor symptoms. The gene coding for the phospholipid phosphatase 3, PLPP3 (formerly PPAP2B or LPP3), maps within the PARK10 locus, a region that has been linked with increased risk to late-onset PD. PLPP3 modulates the levels of a range of bioactive lipids controlling fundamental cellular processes within the central nervous system. Here we show that PLPP3 is enriched in astroglial cells of the adult murine ventral midbrain. Conditional inactivation of Plpp3 using a Nestin::Cre driver results in reduced mesencephalic levels of sphingosine-1-phosphate receptor 1 (S1P(1)), a well-known mediator of pro-survival responses. Yet, adult PLPP3-deficient mice exhibited no alterations in the number of dopaminergic neurons or in the basal levels of striatal extracellular dopamine (DA). Potassium-evoked DA overflow in the striatum, however, was significantly decreased in mutant mice. Locomotor evaluation revealed that, although PLPP3-deficient mice exhibit motor impairment, this is not progressive or responsive to acute L-DOPA therapy. These findings suggest that disruption of Plpp3 during early neural development leads to dopaminergic transmission deficits in the absence of nigrostriatal degeneration, and without causing an age-related locomotor decline consistent with PD. Nature Publishing Group 2016-04-11 /pmc/articles/PMC4827058/ /pubmed/27063549 http://dx.doi.org/10.1038/srep24028 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Gómez-López, Sandra Martínez-Silva, Ana Valeria Montiel, Teresa Osorio-Gómez, Daniel Bermúdez-Rattoni, Federico Massieu, Lourdes Escalante-Alcalde, Diana Neural ablation of the PARK10 candidate Plpp3 leads to dopaminergic transmission deficits without neurodegeneration |
title | Neural ablation of the PARK10 candidate Plpp3 leads to dopaminergic transmission deficits without neurodegeneration |
title_full | Neural ablation of the PARK10 candidate Plpp3 leads to dopaminergic transmission deficits without neurodegeneration |
title_fullStr | Neural ablation of the PARK10 candidate Plpp3 leads to dopaminergic transmission deficits without neurodegeneration |
title_full_unstemmed | Neural ablation of the PARK10 candidate Plpp3 leads to dopaminergic transmission deficits without neurodegeneration |
title_short | Neural ablation of the PARK10 candidate Plpp3 leads to dopaminergic transmission deficits without neurodegeneration |
title_sort | neural ablation of the park10 candidate plpp3 leads to dopaminergic transmission deficits without neurodegeneration |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4827058/ https://www.ncbi.nlm.nih.gov/pubmed/27063549 http://dx.doi.org/10.1038/srep24028 |
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