Optogenetic targeting of astrocytes restores slow brain rhythm function and slows Alzheimer's disease pathology.

Autor: Lee YF; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA.; Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MA, 02118, USA., Russ AN; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Zhao Q; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Perle SJ; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Maci M; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Miller MR; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Hou SS; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Algamal M; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Zhao Z; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Li H; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Gelwan N; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Liu Z; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Gomperts SN; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Araque A; Department of Neuroscience, University of Minnesota, Minneapolis, MN, 55455, USA., Galea E; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA., Bacskai BJ; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA. BBACSKAI@mgh.harvard.edu., Kastanenka KV; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129, USA. KKASTANENKA@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Aug 11; Vol. 13 (1), pp. 13075. Date of Electronic Publication: 2023 Aug 11.
DOI: 10.1038/s41598-023-40402-3
Abstrakt: Patients with Alzheimer's disease (AD) exhibit non-rapid eye movement (NREM) sleep disturbances in addition to memory deficits. Disruption of NREM slow waves occurs early in the disease progression and is recapitulated in transgenic mouse models of beta-amyloidosis. However, the mechanisms underlying slow-wave disruptions remain unknown. Because astrocytes contribute to slow-wave activity, we used multiphoton microscopy and optogenetics to investigate whether they contribute to slow-wave disruptions in APP/PS1 mice. The power but not the frequency of astrocytic calcium transients was reduced in APP/PS1 mice compared to nontransgenic controls. Optogenetic activation of astrocytes at the endogenous frequency of slow waves restored slow-wave power, reduced amyloid deposition, prevented neuronal calcium elevations, and improved memory performance. Our findings revealed malfunction of the astrocytic network driving slow-wave disruptions. Thus, targeting astrocytes to restore circuit activity underlying sleep and memory disruptions in AD could ameliorate disease progression.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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