Cargando…
Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson’s disease
Mitochondrial oxidant stress is widely viewed as critical to pathogenesis in Parkinson’s disease. But the origins of this stress are poorly defined. One possibility is that it arises from the metabolic demands associated with regenerative activity. To test this hypothesis, neurons in the dorsal moto...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2012
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461271/ https://www.ncbi.nlm.nih.gov/pubmed/22941107 http://dx.doi.org/10.1038/nn.3209 |
_version_ | 1782245055865552896 |
---|---|
author | Goldberg, Joshua A. Guzman, Jaime N. Estep, Chad M. Ilijic, Ema Kondapalli, Jyothisri Sanchez-Padilla, Javier Surmeier, D. James |
author_facet | Goldberg, Joshua A. Guzman, Jaime N. Estep, Chad M. Ilijic, Ema Kondapalli, Jyothisri Sanchez-Padilla, Javier Surmeier, D. James |
author_sort | Goldberg, Joshua A. |
collection | PubMed |
description | Mitochondrial oxidant stress is widely viewed as critical to pathogenesis in Parkinson’s disease. But the origins of this stress are poorly defined. One possibility is that it arises from the metabolic demands associated with regenerative activity. To test this hypothesis, neurons in the dorsal motor nucleus of the vagus (DMV), a population cholinergic neurons that shows signs of pathology in the early stages of Parkinson’s disease, were characterized in mouse brain slices. DMV neurons were slow, autonomous pacemakers with broad spikes, leading to calcium entry that was weakly buffered. Using a novel transgenic mouse expressing a redox-sensitive optical probe targeted to the mitochondrial matrix, it was found that calcium entry during pacemaking created a basal mitochondrial oxidant stress. Knocking out DJ-1 – a gene associated with early-onset Parkinson’s disease – exacerbated this stress. These results point to a common mechanism underlying mitochondrial oxidant stress in Parkinson’s disease and a therapeutic strategy to ameliorate it. |
format | Online Article Text |
id | pubmed-3461271 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
record_format | MEDLINE/PubMed |
spelling | pubmed-34612712013-04-01 Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson’s disease Goldberg, Joshua A. Guzman, Jaime N. Estep, Chad M. Ilijic, Ema Kondapalli, Jyothisri Sanchez-Padilla, Javier Surmeier, D. James Nat Neurosci Article Mitochondrial oxidant stress is widely viewed as critical to pathogenesis in Parkinson’s disease. But the origins of this stress are poorly defined. One possibility is that it arises from the metabolic demands associated with regenerative activity. To test this hypothesis, neurons in the dorsal motor nucleus of the vagus (DMV), a population cholinergic neurons that shows signs of pathology in the early stages of Parkinson’s disease, were characterized in mouse brain slices. DMV neurons were slow, autonomous pacemakers with broad spikes, leading to calcium entry that was weakly buffered. Using a novel transgenic mouse expressing a redox-sensitive optical probe targeted to the mitochondrial matrix, it was found that calcium entry during pacemaking created a basal mitochondrial oxidant stress. Knocking out DJ-1 – a gene associated with early-onset Parkinson’s disease – exacerbated this stress. These results point to a common mechanism underlying mitochondrial oxidant stress in Parkinson’s disease and a therapeutic strategy to ameliorate it. 2012-09-02 2012-10 /pmc/articles/PMC3461271/ /pubmed/22941107 http://dx.doi.org/10.1038/nn.3209 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Goldberg, Joshua A. Guzman, Jaime N. Estep, Chad M. Ilijic, Ema Kondapalli, Jyothisri Sanchez-Padilla, Javier Surmeier, D. James Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson’s disease |
title | Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson’s disease |
title_full | Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson’s disease |
title_fullStr | Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson’s disease |
title_full_unstemmed | Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson’s disease |
title_short | Calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in Parkinson’s disease |
title_sort | calcium entry induces mitochondrial oxidant stress in vagal neurons at risk in parkinson’s disease |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461271/ https://www.ncbi.nlm.nih.gov/pubmed/22941107 http://dx.doi.org/10.1038/nn.3209 |
work_keys_str_mv | AT goldbergjoshuaa calciumentryinducesmitochondrialoxidantstressinvagalneuronsatriskinparkinsonsdisease AT guzmanjaimen calciumentryinducesmitochondrialoxidantstressinvagalneuronsatriskinparkinsonsdisease AT estepchadm calciumentryinducesmitochondrialoxidantstressinvagalneuronsatriskinparkinsonsdisease AT ilijicema calciumentryinducesmitochondrialoxidantstressinvagalneuronsatriskinparkinsonsdisease AT kondapallijyothisri calciumentryinducesmitochondrialoxidantstressinvagalneuronsatriskinparkinsonsdisease AT sanchezpadillajavier calciumentryinducesmitochondrialoxidantstressinvagalneuronsatriskinparkinsonsdisease AT surmeierdjames calciumentryinducesmitochondrialoxidantstressinvagalneuronsatriskinparkinsonsdisease |