Astrocyte calcium dysfunction causes early network hyperactivity in Alzheimer's disease.

Autor:	Shah D; Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium. Electronic address: disha.shah@kuleuven.be., Gsell W; Biomedical MRI, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium., Wahis J; Laboratory of Glia Biology, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium., Luckett ES; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven, 3000 Leuven, Belgium., Jamoulle T; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven, 3000 Leuven, Belgium., Vermaercke B; Neuro-electronics Research Flanders, 3000 Leuven, Belgium., Preman P; Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium., Moechars D; Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium., Hendrickx V; Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium., Jaspers T; Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium., Craessaerts K; Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium., Horré K; Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium., Wolfs L; Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium., Fiers M; Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium., Holt M; Laboratory of Glia Biology, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium., Thal DR; Laboratory for Neuropathology, Department of Imaging and Pathology, LBI, KU Leuven, 3000 Leuven, Belgium., Callaerts-Vegh Z; Laboratory of Biological Psychology, KU-Leuven, 3000 Leuven, Belgium., D'Hooge R; Laboratory of Biological Psychology, KU-Leuven, 3000 Leuven, Belgium., Vandenberghe R; Laboratory for Cognitive Neurology, Department of Neurosciences, Leuven Brain Institute (LBI), KU Leuven, 3000 Leuven, Belgium., Himmelreich U; Biomedical MRI, Department of Imaging and Pathology, KU Leuven, 3000 Leuven, Belgium., Bonin V; Neuro-electronics Research Flanders, 3000 Leuven, Belgium., De Strooper B; Laboratory for the Research of Neurodegenerative Diseases, VIB Center for Brain and Disease Research, KU Leuven, 3000 Leuven, Belgium; UK Dementia Research Institute at University College London, WC1E 6BT London, UK. Electronic address: b.destrooper@ucl.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2022 Aug 23; Vol. 40 (8), pp. 111280.
DOI:	10.1016/j.celrep.2022.111280
Abstrakt:	Dysfunctions of network activity and functional connectivity (FC) represent early events in Alzheimer's disease (AD), but the underlying mechanisms remain unclear. Astrocytes regulate local neuronal activity in the healthy brain, but their involvement in early network hyperactivity in AD is unknown. We show increased FC in the human cingulate cortex several years before amyloid deposition. We find the same early cingulate FC disruption and neuronal hyperactivity in App NL-F mice. Crucially, these network disruptions are accompanied by decreased astrocyte calcium signaling. Recovery of astrocytic calcium activity normalizes neuronal hyperactivity and FC, as well as seizure susceptibility and day/night behavioral disruptions. In conclusion, we show that astrocytes mediate initial features of AD and drive clinically relevant phenotypes. Competing Interests: Declaration of interests B.D.S. is the Bax-Vanluffelen Chair for Alzheimer’s Disease and is supported by the Opening the Future campaign and Mission Lucidity of KU-Leuven. D.R.T. received speaker honorarium from Biogen (USA), and collaborated with GE-Healthcare (UK), Novartis Pharma Basel (Switzerland), Probiodrug (Germany), and Janssen Pharmaceutical Companies (Belgium). (Copyright © 2022. Published by Elsevier Inc.)
Databáze:	MEDLINE
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