Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies

Neurons of the nucleus basalis of Meynert (nbM) are vulnerable to Lewy body formation and neuronal loss, which is thought to underlie cognitive dysfunction in Lewy body dementia (LBD). There is continued debate about whether Lewy bodies exert a neurodegenerative effect by affecting mitochondria, or...

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Autores principales: Hatton, Christopher, Reeve, Amy, Lax, Nichola Zoe, Blain, Alasdair, Ng, Yi Shiau, El-Agnaf, Omar, Attems, Johannes, Taylor, John-Paul, Turnbull, Doug, Erskine, Daniel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
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Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346628/
https://www.ncbi.nlm.nih.gov/pubmed/32646480
http://dx.doi.org/10.1186/s40478-020-00985-8
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author Hatton, Christopher
Reeve, Amy
Lax, Nichola Zoe
Blain, Alasdair
Ng, Yi Shiau
El-Agnaf, Omar
Attems, Johannes
Taylor, John-Paul
Turnbull, Doug
Erskine, Daniel
author_facet Hatton, Christopher
Reeve, Amy
Lax, Nichola Zoe
Blain, Alasdair
Ng, Yi Shiau
El-Agnaf, Omar
Attems, Johannes
Taylor, John-Paul
Turnbull, Doug
Erskine, Daniel
author_sort Hatton, Christopher
collection PubMed
description Neurons of the nucleus basalis of Meynert (nbM) are vulnerable to Lewy body formation and neuronal loss, which is thought to underlie cognitive dysfunction in Lewy body dementia (LBD). There is continued debate about whether Lewy bodies exert a neurodegenerative effect by affecting mitochondria, or whether they represent a protective mechanism. Therefore, the present study sought to determine whether the nbM is subject to mitochondrial dysfunctional in LBD and the association of Lewy body formation with such changes. Post-mortem nbM tissue was stained for Complex I or IV and quantitated relative to porin with immunofluorescence using confocal microscopy of individual cells from LBD (303 neurons, 8 cases), control (362 neurons, 8 cases) and asymptomatic incidental LBD (iLBD) cases (99 neurons, 2 cases). Additionally, α-synuclein, tau and amyloid-β pathology were analysed using quantitative immunohistochemistry, and respiratory chain markers were compared in cells with Lewy bodies (N = 134) and unaffected cells (N = 272). The expression of Complex I normalised to mitochondrial mass was significantly lower in LBD compared to control and iLBD cases and this was unrelated to local neuropathological burdens but trended toward a relationship with neuronal loss. Furthermore, Complex I expression was higher in cells with Lewy bodies compared to adjacent cells without α-synuclein aggregates. These findings suggest that Complex I deficits in the nbM occur in symptomatic LBD cases and may relate to neuronal loss, but that contrary to the view that Lewy body formation underlies neuronal dysfunction and damage in LBD, Lewy bodies are associated with higher Complex I expression than neurons without Lewy bodies. One could speculate that Lewy bodies may provide a mechanism to encapsulate damaged mitochondria and/or α-synuclein oligomers, thus protecting neurons from their cytotoxic effects.
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spelling pubmed-73466282020-07-14 Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies Hatton, Christopher Reeve, Amy Lax, Nichola Zoe Blain, Alasdair Ng, Yi Shiau El-Agnaf, Omar Attems, Johannes Taylor, John-Paul Turnbull, Doug Erskine, Daniel Acta Neuropathol Commun Research Neurons of the nucleus basalis of Meynert (nbM) are vulnerable to Lewy body formation and neuronal loss, which is thought to underlie cognitive dysfunction in Lewy body dementia (LBD). There is continued debate about whether Lewy bodies exert a neurodegenerative effect by affecting mitochondria, or whether they represent a protective mechanism. Therefore, the present study sought to determine whether the nbM is subject to mitochondrial dysfunctional in LBD and the association of Lewy body formation with such changes. Post-mortem nbM tissue was stained for Complex I or IV and quantitated relative to porin with immunofluorescence using confocal microscopy of individual cells from LBD (303 neurons, 8 cases), control (362 neurons, 8 cases) and asymptomatic incidental LBD (iLBD) cases (99 neurons, 2 cases). Additionally, α-synuclein, tau and amyloid-β pathology were analysed using quantitative immunohistochemistry, and respiratory chain markers were compared in cells with Lewy bodies (N = 134) and unaffected cells (N = 272). The expression of Complex I normalised to mitochondrial mass was significantly lower in LBD compared to control and iLBD cases and this was unrelated to local neuropathological burdens but trended toward a relationship with neuronal loss. Furthermore, Complex I expression was higher in cells with Lewy bodies compared to adjacent cells without α-synuclein aggregates. These findings suggest that Complex I deficits in the nbM occur in symptomatic LBD cases and may relate to neuronal loss, but that contrary to the view that Lewy body formation underlies neuronal dysfunction and damage in LBD, Lewy bodies are associated with higher Complex I expression than neurons without Lewy bodies. One could speculate that Lewy bodies may provide a mechanism to encapsulate damaged mitochondria and/or α-synuclein oligomers, thus protecting neurons from their cytotoxic effects. BioMed Central 2020-07-09 /pmc/articles/PMC7346628/ /pubmed/32646480 http://dx.doi.org/10.1186/s40478-020-00985-8 Text en © The Author(s) 2020 Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Hatton, Christopher
Reeve, Amy
Lax, Nichola Zoe
Blain, Alasdair
Ng, Yi Shiau
El-Agnaf, Omar
Attems, Johannes
Taylor, John-Paul
Turnbull, Doug
Erskine, Daniel
Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies
title Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies
title_full Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies
title_fullStr Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies
title_full_unstemmed Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies
title_short Complex I reductions in the nucleus basalis of Meynert in Lewy body dementia: the role of Lewy bodies
title_sort complex i reductions in the nucleus basalis of meynert in lewy body dementia: the role of lewy bodies
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346628/
https://www.ncbi.nlm.nih.gov/pubmed/32646480
http://dx.doi.org/10.1186/s40478-020-00985-8
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