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Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease

Hibernation induces neurodegeneration-like changes in the brain, which are completely reversed upon arousal. Hibernation-induced plasticity may therefore be of great relevance for the treatment of neurodegenerative diseases, but remains largely unexplored. Here we show that a single torpor and arous...

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Autores principales: de Veij Mestdagh, Christina F., Timmerman, Jaap A., Koopmans, Frank, Paliukhovich, Iryna, Miedema, Suzanne S. M., Goris, Maaike, van der Loo, Rolinka J., Krenning, Guido, Li, Ka Wan, Mansvelder, Huibert D., Smit, August B., Henning, Robert H., van Kesteren, Ronald E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322095/
https://www.ncbi.nlm.nih.gov/pubmed/34326412
http://dx.doi.org/10.1038/s41598-021-94992-x
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author de Veij Mestdagh, Christina F.
Timmerman, Jaap A.
Koopmans, Frank
Paliukhovich, Iryna
Miedema, Suzanne S. M.
Goris, Maaike
van der Loo, Rolinka J.
Krenning, Guido
Li, Ka Wan
Mansvelder, Huibert D.
Smit, August B.
Henning, Robert H.
van Kesteren, Ronald E.
author_facet de Veij Mestdagh, Christina F.
Timmerman, Jaap A.
Koopmans, Frank
Paliukhovich, Iryna
Miedema, Suzanne S. M.
Goris, Maaike
van der Loo, Rolinka J.
Krenning, Guido
Li, Ka Wan
Mansvelder, Huibert D.
Smit, August B.
Henning, Robert H.
van Kesteren, Ronald E.
author_sort de Veij Mestdagh, Christina F.
collection PubMed
description Hibernation induces neurodegeneration-like changes in the brain, which are completely reversed upon arousal. Hibernation-induced plasticity may therefore be of great relevance for the treatment of neurodegenerative diseases, but remains largely unexplored. Here we show that a single torpor and arousal sequence in mice does not induce dendrite retraction and synapse loss as observed in seasonal hibernators. Instead, it increases hippocampal long-term potentiation and contextual fear memory. This is accompanied by increased levels of key postsynaptic proteins and mitochondrial complex I and IV proteins, indicating mitochondrial reactivation and enhanced synaptic plasticity upon arousal. Interestingly, a single torpor and arousal sequence was also sufficient to restore contextual fear memory in an APP/PS1 mouse model of Alzheimer’s disease. Our study demonstrates that torpor in mice evokes an exceptional state of hippocampal plasticity and that naturally occurring plasticity mechanisms during torpor provide an opportunity to identify unique druggable targets for the treatment of cognitive impairment.
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spelling pubmed-83220952021-07-30 Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease de Veij Mestdagh, Christina F. Timmerman, Jaap A. Koopmans, Frank Paliukhovich, Iryna Miedema, Suzanne S. M. Goris, Maaike van der Loo, Rolinka J. Krenning, Guido Li, Ka Wan Mansvelder, Huibert D. Smit, August B. Henning, Robert H. van Kesteren, Ronald E. Sci Rep Article Hibernation induces neurodegeneration-like changes in the brain, which are completely reversed upon arousal. Hibernation-induced plasticity may therefore be of great relevance for the treatment of neurodegenerative diseases, but remains largely unexplored. Here we show that a single torpor and arousal sequence in mice does not induce dendrite retraction and synapse loss as observed in seasonal hibernators. Instead, it increases hippocampal long-term potentiation and contextual fear memory. This is accompanied by increased levels of key postsynaptic proteins and mitochondrial complex I and IV proteins, indicating mitochondrial reactivation and enhanced synaptic plasticity upon arousal. Interestingly, a single torpor and arousal sequence was also sufficient to restore contextual fear memory in an APP/PS1 mouse model of Alzheimer’s disease. Our study demonstrates that torpor in mice evokes an exceptional state of hippocampal plasticity and that naturally occurring plasticity mechanisms during torpor provide an opportunity to identify unique druggable targets for the treatment of cognitive impairment. Nature Publishing Group UK 2021-07-29 /pmc/articles/PMC8322095/ /pubmed/34326412 http://dx.doi.org/10.1038/s41598-021-94992-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This 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/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
de Veij Mestdagh, Christina F.
Timmerman, Jaap A.
Koopmans, Frank
Paliukhovich, Iryna
Miedema, Suzanne S. M.
Goris, Maaike
van der Loo, Rolinka J.
Krenning, Guido
Li, Ka Wan
Mansvelder, Huibert D.
Smit, August B.
Henning, Robert H.
van Kesteren, Ronald E.
Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease
title Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease
title_full Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease
title_fullStr Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease
title_full_unstemmed Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease
title_short Torpor enhances synaptic strength and restores memory performance in a mouse model of Alzheimer’s disease
title_sort torpor enhances synaptic strength and restores memory performance in a mouse model of alzheimer’s disease
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322095/
https://www.ncbi.nlm.nih.gov/pubmed/34326412
http://dx.doi.org/10.1038/s41598-021-94992-x
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