Journal Article

DZNE-2020-06549

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Metformin reverses early cortical network dysfunction and behavior changes in Huntington's disease.

Arnoux, I. ; Willam, M. ; Griesche, N.DZNE* ; Krummeich, J. ; Watari, H. ; Offermann, N.DZNE* ; Weber, S.DZNE* ; Narayan Dey, P. ; Chen, C. ; Monteiro, O. ; Büttner, S.DZNE* ; Meyer, K.DZNE* ; Bano, D.DZNE* ; Radyushkin, K. ; Langston, R. ; Lambert, J. J. ; Wanker, E. ; Methner, A. ; Krauß, S. (Corresponding author)DZNE* ; Schweiger, S. ; Stroh, A.

2018
eLife Sciences Publications Cambridge

This record in other databases:    

Please use a persistent id in citations: doi:10.7554/eLife.38744

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 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.

Keyword(s): 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) ; Huntingtin Protein ; Mutant Proteins ; Protein Aggregates ; Metformin ; Calcium

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Contributing Institute(s):

1. Regulatory RNA-protein interaction in neurodegenerative diseases (AG Krauß)
2. Aging and Neurodegeneration (AG Bano)
3. Synaptic Connectivity and Neurodegeneration (AG Nicotera)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
2. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2018

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; IF >= 5 ; JCR ; SCOPUS ; Web of Science Core Collection ; Zoological Record

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Linked articles:

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dataset Arnoux, I. ; Willam, M. ; Griesche, N.DZNE* ; Krummeich, J.Extern* ; Watari, H. ; Offermann, N.DZNE* ; Weber, S.DZNE* ; Narayan Dey, P. ; Chen, C. ; Monteiro, O. ; Buettner, S.DZNE* ; Meyer, K.DZNE* ; Bano, D.DZNE* ; Radyushkin, K. ; Langston, R. ; Lambert, J. J.DZNE* ; Wanker, E. ; Methner, A. ; Krauss, S.DZNE* ; Schweiger, S. ; Stroh, A.
Dataset: Data from: Metformin reverses early cortical network dysfunction and behavior changes in Huntington’s disease
Dryad (2018) [10.5061/dryad.g3b5272]2018 BibTeX | EndNote: XML, Text | RIS

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