140227 20240504120055.0 10.7554/eLife.38744 doi pmid:30179155 pmid pmc:PMC6156080 pmc altmetric:47686118 altmetric DZNE-2020-06549 English 600 Arnoux, Isabelle 0 Metformin reverses early cortical network dysfunction and behavior changes in Huntington's disease. Cambridge 2018 eLife Sciences Publications online Crossref eLife Sciences Publications, Ltd 2018-09-04 article DRIVER Output Types/Journal article DataCite Journal Article journal journal PUB:(DE-HGF)16 1714742760_33 PUB:(DE-HGF) ARTICLE BibTeX JOURNAL_ARTICLE ORCID Journal Article 0 EndNote 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 Ca2+ 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. 342 - Disease Mechanisms and Model Systems (POF3-342) G:(DE-HGF)POF3-342 POF3-342 POF III 0 341 - Molecular Signaling (POF3-341) G:(DE-HGF)POF3-341 POF3-341 POF III 1 2018-09-04 Crossref http://creativecommons.org/licenses/by/4.0/ Dataset connected to CrossRef, PubMed, Huntingtin Protein NLM Chemicals Mutant Proteins NLM Chemicals Protein Aggregates NLM Chemicals Metformin 9100L32L2N NLM Chemicals Calcium SY7Q814VUP NLM Chemicals Animals MeSH Astrocytes: drug effects MeSH Astrocytes: metabolism MeSH Behavior, Animal: drug effects MeSH Caenorhabditis elegans: drug effects MeSH Calcium: metabolism MeSH Cell Respiration: drug effects MeSH Cerebral Cortex: drug effects MeSH Cerebral Cortex: physiopathology MeSH Disease Models, Animal MeSH Huntingtin Protein: metabolism MeSH Huntington Disease: pathology MeSH Huntington Disease: physiopathology MeSH Kinetics MeSH Metformin: pharmacology MeSH Mitochondria: drug effects MeSH Mitochondria: metabolism MeSH Mutant Proteins: metabolism MeSH Nerve Net: drug effects MeSH Nerve Net: physiopathology MeSH Neurons: drug effects MeSH Neurons: metabolism MeSH Photons MeSH Protein Aggregates: drug effects MeSH Protein Biosynthesis MeSH Time-Lapse Imaging MeSH Willam, Michael 1 Griesche, Nadine P:(DE-2719)2690834 2 Krummeich, Jennifer P:(DE-HGF)0 3 Watari, Hirofumi 4 Offermann, Nina P:(DE-2719)2811777 5 Weber, Stephanie P:(DE-2719)2662310 6 Narayan Dey, Partha 7 Chen, Changwei 8 Monteiro, Olivia 9 Büttner, Sven P:(DE-2719)2809898 10 Meyer, Katharina P:(DE-2719)2401927 11 Bano, Daniele P:(DE-2719)2158358 12 Radyushkin, Konstantin 13 Langston, Rosamund 14 Lambert, Jeremy J 15 Wanker, Erich 16 Methner, Axel 17 Krauß, Sybille P:(DE-2719)2421562 18 Corresponding author dzne Schweiger, Susann 19 Stroh, Albrecht 20 10.7554/elife.38744 : eLife Sciences Publications, Ltd, 2018-09-04 journal-article Crossref eLife 7 2018 2050-084X 10.7554/eLife.38744 Vol. 7, p. e38744 PERI:(DE-600)2687154-3 7<e38744 e38744 eLife 7 2018 2050-084X Arnoux, Isabelle et.al. Dryad, 2018 RelatedTo DZNE-2022-01789 Data from: Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease OpenAccess http://pub.dzne.de/record/140227/files/DZNE-2020-06549.pdf OpenAccess pdfa http://pub.dzne.de/record/140227/files/DZNE-2020-06549.pdf?subformat=pdfa Pubmed Central http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6156080 oai:pub.dzne.de:140227 openaire open_access VDB driver dnbdelivery Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2690834 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 5 P:(DE-2719)2811777 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 6 P:(DE-2719)2662310 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 10 P:(DE-2719)2809898 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 11 P:(DE-2719)2401927 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 12 P:(DE-2719)2158358 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 18 P:(DE-2719)2421562 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-342 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Disease Mechanisms and Model Systems 0 DE-HGF Gesundheit Erkrankungen des Nervensystems G:(DE-HGF)POF3-340 G:(DE-HGF)POF3-341 G:(DE-HGF)POF3 G:(DE-HGF)POF3-300 G:(DE-HGF)POF Molecular Signaling 1 2018 DBCoverage StatID:(DE-HGF)0200 StatID SCOPUS 2022-11-23 Creative Commons Attribution CC BY (No Version) LIC:(DE-HGF)CCBYNV V:(DE-HGF) DOAJ DBCoverage StatID:(DE-HGF)1050 StatID BIOSIS Previews 2022-11-23 DBCoverage StatID:(DE-HGF)0600 StatID Ebsco Academic Search 2022-11-23 DBCoverage StatID:(DE-HGF)1040 StatID Zoological Record 2022-11-23 JCR StatID:(DE-HGF)0100 StatID ELIFE : 2021 2022-11-23 DBCoverage StatID:(DE-HGF)0501 StatID DOAJ Seal 2022-09-23T12:20:44Z DBCoverage StatID:(DE-HGF)0500 StatID DOAJ 2022-09-23T12:20:44Z DBCoverage StatID:(DE-HGF)0150 StatID Web of Science Core Collection 2022-11-23 OpenAccess StatID:(DE-HGF)0510 StatID Peer Review StatID:(DE-HGF)0030 StatID ASC 2022-11-23 IF >= 5 StatID:(DE-HGF)9905 StatID ELIFE : 2021 2022-11-23 DBCoverage StatID:(DE-HGF)0300 StatID Medline 2022-11-23 DBCoverage StatID:(DE-HGF)0199 StatID Clarivate Analytics Master Journal List 2022-11-23 I:(DE-2719)1011006 AG Krauß Regulatory RNA-protein interaction in neurodegenerative diseases 0 I:(DE-2719)1013003 AG Bano Aging and Neurodegeneration 1 I:(DE-2719)5000018 AG Nicotera Synaptic Connectivity and Neurodegeneration 2 journal VDB UNRESTRICTED I:(DE-2719)1011006 I:(DE-2719)1013003 I:(DE-2719)5000018 FullTexts -- missing cx lookup -- 10.1016/j.brainresbull.2010.05.004 Crossref 10.1016/j.brainresbull.2010.05.004 -- missing cx lookup -- 10.1126/science.1162844 Crossref 10.1126/science.1162844 -- missing cx lookup -- 10.1073/pnas.1206171109 Crossref 10.1073/pnas.1206171109 -- missing cx 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