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000140227 245__ $$aMetformin reverses early cortical network dysfunction and behavior changes in Huntington's disease.
000140227 260__ $$aCambridge$$beLife Sciences Publications$$c2018
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000140227 520__ $$aCatching primal functional changes in early, 'very far from disease onset' (VFDO) stages of Huntington's disease is likely to be the key to a successful therapy. Focusing on VFDO stages, we assessed neuronal microcircuits in premanifest Hdh150 knock-in mice. Employing in vivo two-photon Ca2+ imaging, we revealed an early pattern of circuit dysregulation in the visual cortex - one of the first regions affected in premanifest Huntington's disease - characterized by an increase in activity, an enhanced synchronicity and hyperactive neurons. These findings are accompanied by aberrations in animal behavior. We furthermore show that the antidiabetic drug metformin diminishes aberrant Huntingtin protein load and fully restores both early network activity patterns and behavioral aberrations. This network-centered approach reveals a critical window of vulnerability far before clinical manifestation and establishes metformin as a promising candidate for a chronic therapy starting early in premanifest Huntington's disease pathogenesis long before the onset of clinical symptoms.
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000140227 650_7 $$2NLM Chemicals$$aHuntingtin Protein
000140227 650_7 $$2NLM Chemicals$$aMutant Proteins
000140227 650_7 $$2NLM Chemicals$$aProtein Aggregates
000140227 650_7 $$09100L32L2N$$2NLM Chemicals$$aMetformin
000140227 650_7 $$0SY7Q814VUP$$2NLM Chemicals$$aCalcium
000140227 650_2 $$2MeSH$$aAnimals
000140227 650_2 $$2MeSH$$aAstrocytes: drug effects
000140227 650_2 $$2MeSH$$aAstrocytes: metabolism
000140227 650_2 $$2MeSH$$aBehavior, Animal: drug effects
000140227 650_2 $$2MeSH$$aCaenorhabditis elegans: drug effects
000140227 650_2 $$2MeSH$$aCalcium: metabolism
000140227 650_2 $$2MeSH$$aCell Respiration: drug effects
000140227 650_2 $$2MeSH$$aCerebral Cortex: drug effects
000140227 650_2 $$2MeSH$$aCerebral Cortex: physiopathology
000140227 650_2 $$2MeSH$$aDisease Models, Animal
000140227 650_2 $$2MeSH$$aHuntingtin Protein: metabolism
000140227 650_2 $$2MeSH$$aHuntington Disease: pathology
000140227 650_2 $$2MeSH$$aHuntington Disease: physiopathology
000140227 650_2 $$2MeSH$$aKinetics
000140227 650_2 $$2MeSH$$aMetformin: pharmacology
000140227 650_2 $$2MeSH$$aMitochondria: drug effects
000140227 650_2 $$2MeSH$$aMitochondria: metabolism
000140227 650_2 $$2MeSH$$aMutant Proteins: metabolism
000140227 650_2 $$2MeSH$$aNerve Net: drug effects
000140227 650_2 $$2MeSH$$aNerve Net: physiopathology
000140227 650_2 $$2MeSH$$aNeurons: drug effects
000140227 650_2 $$2MeSH$$aNeurons: metabolism
000140227 650_2 $$2MeSH$$aPhotons
000140227 650_2 $$2MeSH$$aProtein Aggregates: drug effects
000140227 650_2 $$2MeSH$$aProtein Biosynthesis
000140227 650_2 $$2MeSH$$aTime-Lapse Imaging
000140227 7001_ $$aWillam, Michael$$b1
000140227 7001_ $$0P:(DE-2719)2690834$$aGriesche, Nadine$$b2
000140227 7001_ $$0P:(DE-HGF)0$$aKrummeich, Jennifer$$b3
000140227 7001_ $$aWatari, Hirofumi$$b4
000140227 7001_ $$0P:(DE-2719)2811777$$aOffermann, Nina$$b5
000140227 7001_ $$0P:(DE-2719)2662310$$aWeber, Stephanie$$b6
000140227 7001_ $$aNarayan Dey, Partha$$b7
000140227 7001_ $$aChen, Changwei$$b8
000140227 7001_ $$aMonteiro, Olivia$$b9
000140227 7001_ $$0P:(DE-2719)2809898$$aBüttner, Sven$$b10
000140227 7001_ $$0P:(DE-2719)2401927$$aMeyer, Katharina$$b11
000140227 7001_ $$0P:(DE-2719)2158358$$aBano, Daniele$$b12
000140227 7001_ $$aRadyushkin, Konstantin$$b13
000140227 7001_ $$aLangston, Rosamund$$b14
000140227 7001_ $$aLambert, Jeremy J$$b15
000140227 7001_ $$aWanker, Erich$$b16
000140227 7001_ $$aMethner, Axel$$b17
000140227 7001_ $$0P:(DE-2719)2421562$$aKrauß, Sybille$$b18$$eCorresponding author$$udzne
000140227 7001_ $$aSchweiger, Susann$$b19
000140227 7001_ $$aStroh, Albrecht$$b20
000140227 77318 $$2Crossref$$3journal-article$$a10.7554/elife.38744$$b : eLife Sciences Publications, Ltd, 2018-09-04$$teLife$$v7$$x2050-084X$$y2018
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