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Arnoux 2018 Elife
Additional label Labels  + , 2018-11  +
Coupling states LEAK  + , OXPHOS  + , ET  +
Diseases Inherited  + , Neurodegenerative  +
Has abstract Catching primal functional changes in earl
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 Ca<sup>2+</sup> 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.
ong before the onset of clinical symptoms.  +
Has editor [[Plangger M]]  +
Has info [ PMID: 30179155]  +
Has publicationkeywords C. elegans  + , Huntington disease  + , Cortical microcircuits  + , In vivo calcium imaging  + , Metformin  + , Mouse  + , Neuronal hyperactivity  + , Neuroscience  +
Has title Arnoux I, Willam M, Griesche N, Krummeich
Arnoux I, Willam M, Griesche N, Krummeich J, Watari H, Offermann N, Weber S, Narayan Dey P, Chen C, Monteiro O, Buettner S, Meyer K, Bano D, Radyushkin K, Langston R, Lambert JJ, Wanker E, Methner A, Krauss S, Schweiger S, Stroh A (2018) Metformin reverses early cortical network dysfunction and behavior changes in Huntington's disease. Elife 7:e38744.
s in Huntington's disease. Elife 7:e38744.  +
Instrument and method Oxygraph-2k  +
Mammal and model Mouse  +
MiP area Respiration  + , Pharmacology;toxicology  +
Pathways N  + , S  + , NS  + , ROX  +
Preparation Homogenate  +
Tissue and cell Nervous system  +
Was published by MiPNetLab DE Ulm Radermacher P + , DE Mainz Methner A +
Was published in journal Elife +
Was published in year 2018  +
Was written by Arnoux I + , Willam M + , Griesche N + , Krummeich J + , Watari H + , Offermann N + , Weber S + , Narayan Dey P + , Chen C + , Monteiro O + , Buettner S + , Meyer K + , Bano D + , Radyushkin K + , Langston R + , Lambert JJ + , Wanker E + , Methner A + , Krauss S + , Schweiger S + , Stroh A +
Categories Publications
Modification date
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13:44:17, 6 November 2018  +
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