Exposure to 3-Nitropropionic Acid Mitochondrial Toxin Induces Tau Pathology in Tangle-Mouse Model and in Wild Type-Mice
Oxidative stress, particularly of mitochondrial origin, plays an important role in the pathogenesis of neurodegenerative disorders, including Alzheimer’s disease (AD) and other tauopathies. Controversies regarding the responses of tau phosphorylation state to various stimuli causing oxidative stress...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcell.2019.00321/full |
| _version_ | 1818880762350403584 |
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| author | Inbal Lahiani-Cohen Olga Touloumi Roza Lagoudaki Nikolaos Grigoriadis Hanna Rosenmann |
| author_facet | Inbal Lahiani-Cohen Olga Touloumi Roza Lagoudaki Nikolaos Grigoriadis Hanna Rosenmann |
| author_sort | Inbal Lahiani-Cohen |
| collection | DOAJ |
| description | Oxidative stress, particularly of mitochondrial origin, plays an important role in the pathogenesis of neurodegenerative disorders, including Alzheimer’s disease (AD) and other tauopathies. Controversies regarding the responses of tau phosphorylation state to various stimuli causing oxidative stress have been reported. Here we investigated the effect of 3-nitropropionic acid (3NP), a mitochondrial toxin which induces oxidative stress, on the tangle-pathology in our previously generated double mutant (E257T/P301S, DM) -Tau-tg mice and in WT-mice. We detected an increase in tangle pathology in the hippocampus and cortex of the DM-Tau-tg mice following exposure of the mice to the toxin, as well as generation of tangles in WT-mice. This increase was accompanied with alterations in the level of the glycogen synthase kinase 3β (GSK3β), the kinase which phosphorylates the tau protein, and in the phosphorylation state of this kinase. A response of microglial cells was noticed. These results point to the involvement of mitochondrial dysfunction in the development of the tangle-pathology and may suggest that interfering with mitochondrial dysfunction may have an anti-tangle therapeutic potential. |
| first_indexed | 2024-12-19T14:51:07Z |
| format | Article |
| id | doaj.art-0353fa81e1414b90bc8cd6ebfef48aa3 |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-19T14:51:07Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-0353fa81e1414b90bc8cd6ebfef48aa32022-12-21T20:16:49ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2020-01-01710.3389/fcell.2019.00321476639Exposure to 3-Nitropropionic Acid Mitochondrial Toxin Induces Tau Pathology in Tangle-Mouse Model and in Wild Type-MiceInbal Lahiani-Cohen0Olga Touloumi1Roza Lagoudaki2Nikolaos Grigoriadis3Hanna Rosenmann4The Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, IsraelB’ Department of Neurology, AHEPA University Hospital, Thessaloniki, GreeceB’ Department of Neurology, AHEPA University Hospital, Thessaloniki, GreeceB’ Department of Neurology, AHEPA University Hospital, Thessaloniki, GreeceThe Department of Neurology, The Agnes Ginges Center for Human Neurogenetics, Hadassah Hebrew University Medical Center, Jerusalem, IsraelOxidative stress, particularly of mitochondrial origin, plays an important role in the pathogenesis of neurodegenerative disorders, including Alzheimer’s disease (AD) and other tauopathies. Controversies regarding the responses of tau phosphorylation state to various stimuli causing oxidative stress have been reported. Here we investigated the effect of 3-nitropropionic acid (3NP), a mitochondrial toxin which induces oxidative stress, on the tangle-pathology in our previously generated double mutant (E257T/P301S, DM) -Tau-tg mice and in WT-mice. We detected an increase in tangle pathology in the hippocampus and cortex of the DM-Tau-tg mice following exposure of the mice to the toxin, as well as generation of tangles in WT-mice. This increase was accompanied with alterations in the level of the glycogen synthase kinase 3β (GSK3β), the kinase which phosphorylates the tau protein, and in the phosphorylation state of this kinase. A response of microglial cells was noticed. These results point to the involvement of mitochondrial dysfunction in the development of the tangle-pathology and may suggest that interfering with mitochondrial dysfunction may have an anti-tangle therapeutic potential.https://www.frontiersin.org/article/10.3389/fcell.2019.00321/fulltau proteinneurofibrillary tanglestauopathymitochondriamitochondrial dysfunctionoxidative stress |
| spellingShingle | Inbal Lahiani-Cohen Olga Touloumi Roza Lagoudaki Nikolaos Grigoriadis Hanna Rosenmann Exposure to 3-Nitropropionic Acid Mitochondrial Toxin Induces Tau Pathology in Tangle-Mouse Model and in Wild Type-Mice Frontiers in Cell and Developmental Biology tau protein neurofibrillary tangles tauopathy mitochondria mitochondrial dysfunction oxidative stress |
| title | Exposure to 3-Nitropropionic Acid Mitochondrial Toxin Induces Tau Pathology in Tangle-Mouse Model and in Wild Type-Mice |
| title_full | Exposure to 3-Nitropropionic Acid Mitochondrial Toxin Induces Tau Pathology in Tangle-Mouse Model and in Wild Type-Mice |
| title_fullStr | Exposure to 3-Nitropropionic Acid Mitochondrial Toxin Induces Tau Pathology in Tangle-Mouse Model and in Wild Type-Mice |
| title_full_unstemmed | Exposure to 3-Nitropropionic Acid Mitochondrial Toxin Induces Tau Pathology in Tangle-Mouse Model and in Wild Type-Mice |
| title_short | Exposure to 3-Nitropropionic Acid Mitochondrial Toxin Induces Tau Pathology in Tangle-Mouse Model and in Wild Type-Mice |
| title_sort | exposure to 3 nitropropionic acid mitochondrial toxin induces tau pathology in tangle mouse model and in wild type mice |
| topic | tau protein neurofibrillary tangles tauopathy mitochondria mitochondrial dysfunction oxidative stress |
| url | https://www.frontiersin.org/article/10.3389/fcell.2019.00321/full |
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