Data from: Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease

Arnoux, Isabelle, University Medical Center

Willam, Michael, University Medical Center

Griesche, Nadine, German Center for Neurodegenerative Diseases

Krummeich, Jennifer, University Medical Center

Watari, Hirofumi, University Medical Center

Offermann, Nina, German Center for Neurodegenerative Diseases

Weber, Stephanie, German Center for Neurodegenerative Diseases

Narayan Dey, Partha, University Medical Center

Chen, Chen, Institute for Human Genetics, University Medical Center, Mainz, Germany

Monteiro, Olivia, Ninewells Hospital

Buettner, Sven, German Center for Neurodegenerative Diseases

Meyer, Katharina, German Center for Neurodegenerative Diseases

Bano, Daniele, German Center for Neurodegenerative Diseases

Radyushkin, Konstantin, University Medical Center

Langston, Rosamund, University Medical Center

Lambert, Jeremy J., German Center for Neurodegenerative Diseases

Wanker, Erich, Institute of Pathophysiology, Focus Program Translational Neurosciences, University Medical Center, Mainz, Germany

Methner, Axel, University Medical Center

Krauss, Sybille, German Center for Neurodegenerative Diseases

Schweiger, Susann, University Medical Center

Stroh, Albrecht, University Medical Center

Published Sep 05, 2018 on Dryad. https://doi.org/10.5061/dryad.g3b5272

Cite this dataset

Arnoux, Isabelle et al. (2018). Data from: Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease [Dataset]. Dryad. https://doi.org/10.5061/dryad.g3b5272

Abstract

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.

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