169082 20250127124930.0 10.5061/DRYAD.G3B5272 doi 10.5061/dryad.g3b5272 doi DZNE-2022-01789 English Arnoux, Isabelle 0 Dataset: Data from: Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease 2018 Dryad MISC BibTeX Dataset dataset dataset PUB:(DE-HGF)32 1737978554_6605 PUB:(DE-HGF) Chart or Table 26 EndNote Dataset DataCite DATA_SET ORCID ResearchData DINI 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 anti-diabetic 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. 351 - Brain Function (POF4-351) G:(DE-HGF)POF4-351 POF4-351 POF IV 0 352 - Disease Mechanisms (POF4-352) G:(DE-HGF)POF4-352 POF4-352 POF IV 1 Dataset connected to DataCite cortical microcircuits Other Huntington disease Other in vivo calcium imaging Other metformin Other neuronal hyperactivity Other Willam, Michael 1 Griesche, Nadine P:(DE-2719)2690834 2 dzne Krummeich, Jennifer P:(DE-2719)2812064 3 dzne Watari, Hirofumi 4 Offermann, Nina P:(DE-2719)2811777 5 dzne Weber, Stephanie P:(DE-2719)2662310 6 dzne Narayan Dey, Partha 7 Chen, Chen 8 Monteiro, Olivia 9 Buettner, Sven P:(DE-2719)2809898 10 dzne Meyer, Katharina P:(DE-2719)2401927 11 dzne Bano, Daniele P:(DE-2719)2158358 12 dzne Radyushkin, Konstantin 13 Langston, Rosamund 14 Lambert, Jeremy J. P:(DE-HGF)0 15 Wanker, Erich 16 Methner, Axel 17 Krauss, Sybille P:(DE-2719)2421562 18 dzne Schweiger, Susann 19 Stroh, Albrecht 20 10.5061/dryad.g3b5272 VDB oai:pub.dzne.de:169082 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 2 P:(DE-2719)2690834 External Institute I:(DE-HGF)0 Extern 3 P:(DE-2719)2812064 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 15 P:(DE-HGF)0 Deutsches Zentrum für Neurodegenerative Erkrankungen I:(DE-588)1065079516 DZNE 18 P:(DE-2719)2421562 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-351 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Brain Function 0 DE-HGF Gesundheit Neurodegenerative Diseases G:(DE-HGF)POF4-350 G:(DE-HGF)POF4-352 G:(DE-HGF)POF4 G:(DE-HGF)POF4-300 G:(DE-HGF)POF Disease Mechanisms 1 2018 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)1013033 AG Capasso Immune Regulation 2 I:(DE-2719)1040300 Biorepository Biorepository 3 dataset VDB I:(DE-2719)1011006 I:(DE-2719)1013003 I:(DE-2719)1013033 I:(DE-2719)1040300 UNRESTRICTED