TY  - CHART
AU  - Arnoux, Isabelle
AU  - Willam, Michael
AU  - Griesche, Nadine
AU  - Krummeich, Jennifer
AU  - Watari, Hirofumi
AU  - Offermann, Nina
AU  - Weber, Stephanie
AU  - Narayan Dey, Partha
AU  - Chen, Chen
AU  - Monteiro, Olivia
AU  - Buettner, Sven
AU  - Meyer, Katharina
AU  - Bano, Daniele
AU  - Radyushkin, Konstantin
AU  - Langston, Rosamund
AU  - Lambert, Jeremy J.
AU  - Wanker, Erich
AU  - Methner, Axel
AU  - Krauss, Sybille
AU  - Schweiger, Susann
AU  - Stroh, Albrecht
TI  - Dataset: Data from: Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease
PB  - Dryad
M1  - DZNE-2022-01789
PY  - 2018
AB  - 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.
KW  - cortical microcircuits (Other)
KW  - Huntington disease (Other)
KW  - in vivo calcium imaging (Other)
KW  - metformin (Other)
KW  - neuronal hyperactivity (Other)
LB  - PUB:(DE-HGF)32
DO  - DOI:10.5061/dryad.g3b5272
UR  - https://pub.dzne.de/record/169082
ER  -