Evidence map›Paper›PMID 38041158›Full record

ArticleMolecular neurodegeneration2023

Sleep restoration by optogenetic targeting of GABAergic neurons reprograms microglia and ameliorates pathological phenotypes in an Alzheimer's disease model.

Qiuchen Zhao, Megi Maci, Morgan R Miller, Heng Zhou, Fang Zhang, Moustafa Algamal, Yee Fun Lee, Steven S Hou, Stephen J Perle, Hoang Le and 6 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular neurodegeneration, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed, 1 pooled it
7.0field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Article
  7. Review
  8. Article
  9. Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026
    Review
  10. Zolpidem restores sleep and decreases amyloid in a mouse model.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  11. Review
  12. Article
  13. Review
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  15. Article
  16. Article
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  18. Neural bridging achieves transcutaneous regulation of vagus nerve function and treatment of depressive disorders.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Qiuchen ZhaoDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Megi MaciDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Morgan R MillerDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Heng ZhouDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Fang ZhangDepartments of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Moustafa AlgamalDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Yee Fun LeeDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Steven S HouDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Stephen J PerleDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Hoang LeDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Alyssa N RussDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Eng H LoDepartments of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Dmitry GerashchenkoDepartment of Psychiatry, Harvard Medical School and Veterans Affairs Boston Healthcare System, West Roxbury, MA, 02132, USA.
Stephen N GompertsDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Brian J BacskaiDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA.
Ksenia V KastanenkaDepartment of Neurology, MassGeneral Institute of Neurodegenerative Diseases, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA, 02129, USA. KKASTANENKA@mgh.harvard.edu.ORCID 0000-0002-3727-0317
Harvard University · US

Funding

Slow-wave activity as a modifier of the progression of neurodegeneration in Alzheimer's diseaseRF1AG061774 · NIA · HARVARD MEDICAL SCHOOL · PI BACSKAI, BRIAN J, GERASHCHENKO, DMITRY · 2019 to 2021
$3.7M
Elucidating circuit disruptions in Alzheimer's diseaseR01AG066171 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI KASTANENKA, KSENIA V. · 2020 to 2024
$2.9M
Alzheimer's Association AARG-18-52336NIA NIH HHS R01 AG066171NIA NIH HHS RF1 AG061774NIA NIH HHS RF1AG061774-01
6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD) patients exhibit memory disruptions and profound sleep disturbances, including disruption of deep non-rapid eye movement (NREM) sleep. Slow-wave activity (SWA) is a major restorative feature of NREM sleep and is important for memory consolidation.

methodsWe generated a mouse model where GABAergic interneurons could be targeted in the presence of APPswe/PS1dE9 (APP) amyloidosis, APP-GAD-Cre mice. An electroencephalography (EEG) / electromyography (EMG) telemetry system was used to monitor sleep disruptions in these animals. Optogenetic stimulation of GABAergic interneurons in the anterior cortex targeted with channelrhodopsin-2 (ChR2) allowed us to examine the role GABAergic interneurons play in sleep deficits. We also examined the effect of optogenetic stimulation on amyloid plaques, neuronal calcium as well as sleep-dependent memory consolidation. In addition, microglial morphological features and functions were assessed using confocal microscopy and flow cytometry. Finally, we performed sleep deprivation during optogenetic stimulation to investigate whether sleep restoration was necessary to slow AD progression.

resultsAPP-GAD-Cre mice exhibited impairments in sleep architecture including decreased time spent in NREM sleep, decreased delta power, and increased sleep fragmentation compared to nontransgenic (NTG) NTG-GAD-Cre mice. Optogenetic stimulation of cortical GABAergic interneurons increased SWA and rescued sleep impairments in APP-GAD-Cre animals. Furthermore, it slowed AD progression by reducing amyloid deposition, normalizing neuronal calcium homeostasis, and improving memory function. These changes were accompanied by increased numbers and a morphological transformation of microglia, elevated phagocytic marker expression, and enhanced amyloid β (Aβ) phagocytic activity of microglia. Sleep was necessary for amelioration of pathophysiological phenotypes in APP-GAD-Cre mice.

conclusionsIn summary, our study shows that optogenetic targeting of GABAergic interneurons rescues sleep, which then ameliorates neuropathological as well as behavioral deficits by increasing clearance of Aβ by microglia in an AD mouse model.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsCalciumDisease Models, AnimalGABAergic NeuronsHumansMiceMice, TransgenicMicrogliaOptogeneticsSleepAmyloid beta-PeptidesAmyloid beta-Protein PrecursorCalciumAlzheimer’s diseaseEEGMemory consolidationMicrogliaMultiphoton microscopyOptogeneticsSleepSleep deprivationSlow oscillations

Identifiers

PMID38041158
PMCPMC10693059
OpenAlexW4389224616

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.