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Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease
Catching primal functional changes in early, ‘very far from disease onset’ (VFDO) stages of Huntington’s disease is likely to be the key to a successful therapy. Focusing on VFDO stages, we assessed neuronal microcircuits in premanifest Hdh150 knock-in mice. Employing in vivo two-photon Ca(2+) imagi...
Autores principales: | , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156080/ https://www.ncbi.nlm.nih.gov/pubmed/30179155 http://dx.doi.org/10.7554/eLife.38744 |
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author | Arnoux, Isabelle Willam, Michael Griesche, Nadine Krummeich, Jennifer Watari, Hirofumi Offermann, Nina Weber, Stephanie Narayan Dey, Partha Chen, Changwei Monteiro, Olivia Buettner, Sven Meyer, Katharina Bano, Daniele Radyushkin, Konstantin Langston, Rosamund Lambert, Jeremy J Wanker, Erich Methner, Axel Krauss, Sybille Schweiger, Susann Stroh, Albrecht |
author_facet | Arnoux, Isabelle Willam, Michael Griesche, Nadine Krummeich, Jennifer Watari, Hirofumi Offermann, Nina Weber, Stephanie Narayan Dey, Partha Chen, Changwei Monteiro, Olivia Buettner, Sven Meyer, Katharina Bano, Daniele Radyushkin, Konstantin Langston, Rosamund Lambert, Jeremy J Wanker, Erich Methner, Axel Krauss, Sybille Schweiger, Susann Stroh, Albrecht |
author_sort | Arnoux, Isabelle |
collection | PubMed |
description | Catching primal functional changes in early, ‘very far from disease onset’ (VFDO) stages of Huntington’s disease is likely to be the key to a successful therapy. Focusing on VFDO stages, we assessed neuronal microcircuits in premanifest Hdh150 knock-in mice. Employing in vivo two-photon Ca(2+) imaging, we revealed an early pattern of circuit dysregulation in the visual cortex - one of the first regions affected in premanifest Huntington’s disease - characterized by an increase in activity, an enhanced synchronicity and hyperactive neurons. These findings are accompanied by aberrations in animal behavior. We furthermore show that the antidiabetic drug metformin diminishes aberrant Huntingtin protein load and fully restores both early network activity patterns and behavioral aberrations. This network-centered approach reveals a critical window of vulnerability far before clinical manifestation and establishes metformin as a promising candidate for a chronic therapy starting early in premanifest Huntington’s disease pathogenesis long before the onset of clinical symptoms. |
format | Online Article Text |
id | pubmed-6156080 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-61560802018-09-25 Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease Arnoux, Isabelle Willam, Michael Griesche, Nadine Krummeich, Jennifer Watari, Hirofumi Offermann, Nina Weber, Stephanie Narayan Dey, Partha Chen, Changwei Monteiro, Olivia Buettner, Sven Meyer, Katharina Bano, Daniele Radyushkin, Konstantin Langston, Rosamund Lambert, Jeremy J Wanker, Erich Methner, Axel Krauss, Sybille Schweiger, Susann Stroh, Albrecht eLife Neuroscience Catching primal functional changes in early, ‘very far from disease onset’ (VFDO) stages of Huntington’s disease is likely to be the key to a successful therapy. Focusing on VFDO stages, we assessed neuronal microcircuits in premanifest Hdh150 knock-in mice. Employing in vivo two-photon Ca(2+) imaging, we revealed an early pattern of circuit dysregulation in the visual cortex - one of the first regions affected in premanifest Huntington’s disease - characterized by an increase in activity, an enhanced synchronicity and hyperactive neurons. These findings are accompanied by aberrations in animal behavior. We furthermore show that the antidiabetic drug metformin diminishes aberrant Huntingtin protein load and fully restores both early network activity patterns and behavioral aberrations. This network-centered approach reveals a critical window of vulnerability far before clinical manifestation and establishes metformin as a promising candidate for a chronic therapy starting early in premanifest Huntington’s disease pathogenesis long before the onset of clinical symptoms. eLife Sciences Publications, Ltd 2018-09-04 /pmc/articles/PMC6156080/ /pubmed/30179155 http://dx.doi.org/10.7554/eLife.38744 Text en © 2018, Arnoux et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Neuroscience Arnoux, Isabelle Willam, Michael Griesche, Nadine Krummeich, Jennifer Watari, Hirofumi Offermann, Nina Weber, Stephanie Narayan Dey, Partha Chen, Changwei Monteiro, Olivia Buettner, Sven Meyer, Katharina Bano, Daniele Radyushkin, Konstantin Langston, Rosamund Lambert, Jeremy J Wanker, Erich Methner, Axel Krauss, Sybille Schweiger, Susann Stroh, Albrecht Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease |
title | Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease |
title_full | Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease |
title_fullStr | Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease |
title_full_unstemmed | Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease |
title_short | Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease |
title_sort | metformin reverses early cortical network dysfunction and behavior changes in huntington’s disease |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156080/ https://www.ncbi.nlm.nih.gov/pubmed/30179155 http://dx.doi.org/10.7554/eLife.38744 |
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