Optogenetic targeting of cortical astrocytes selectively improves NREM sleep in an Alzheimer's disease mouse model.

Autor: Zhao Q; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA., Yokomizo S; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA., Perle SJ; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA., Lee YF; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA., Zhou H; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA., Miller MR; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA., Li H; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA., Gerashchenko D; Department of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, West Roxbury, MA, 02132, USA., Gomperts SN; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA., Bacskai BJ; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA., Kastanenka KV; Department of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA. kkastanenka@mgh.harvard.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2024 Oct 04; Vol. 14 (1), pp. 23044. Date of Electronic Publication: 2024 Oct 04.
DOI: 10.1038/s41598-024-73082-8
Abstrakt: Alzheimer's disease (AD) is a progressive neurodegenerative condition marked by memory impairments and distinct histopathological features such as amyloid-beta (Aβ) accumulations. Alzheimer's patients experience sleep disturbances at early stages of the disease. APPswe/PS1dE9 (APP) mice exhibit sleep disruptions, including reductions in non-rapid eye movement (NREM) sleep, that contribute to their disease progression. In addition, astrocytic calcium transients associated with a sleep-dependent brain rhythm, slow oscillations prevalent during NREM sleep, are disrupted in APP mice. However, at present it is unclear whether restoration of circuit function by targeting astrocytic activity could improve sleep in APP mice. To that end, APP mice expressing channelrhodopsin-2 (ChR2) targeted to astrocytes underwent optogenetic stimulation at the slow oscillation frequency. Optogenetic stimulation of astrocytes significantly increased NREM sleep duration but not duration of rapid eye movement (REM) sleep. Optogenetic treatment increased delta power and reduced sleep fragmentation in APP mice. Thus, optogenetic activation of astrocytes increased sleep quantity and improved sleep quality in an AD mouse model. Astrocytic activity provides a novel therapeutic avenue to pursue for enhancing sleep and slowing AD progression.
(© 2024. The Author(s).)
Databáze: MEDLINE
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