Evidence map›Paper›PMID 42298296›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2026

Epigenetically driven impairment of BDNF-ARC signaling contributes to circadian and cognitive disarray in a mouse model of postoperative delirium.

Hari Prasad Osuru, Navya Atluri, Tam Le, Jinny Park, Michal Jedrusiak, Elzbieta Dulko, Meghana Illendula, Nadia Lunardi

Abstract read
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In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

8 authors.

Hari Prasad OsuruDepartment of Anesthesiology, University of Virginia Health, Charlottesville, USA.ORCID https://orcid.org/0000-0003-3741-7048
Navya AtluriDepartment of Anesthesiology, University of Virginia Health, Charlottesville, USA.
Tam LeDepartment of Anesthesiology, University of Virginia Health, Charlottesville, USA.
Jinny ParkDepartment of Anesthesiology, University of Virginia Health, Charlottesville, USA.
Michal JedrusiakDepartment of Anesthesiology, University of Virginia Health, Charlottesville, USA.
Elzbieta DulkoDepartment of Anesthesiology, University of Virginia Health, Charlottesville, USA.
Meghana IllendulaDepartment of Anesthesiology, University of Virginia Health, Charlottesville, USA.
Nadia LunardiDepartment of Anesthesiology, University of Virginia Health, Charlottesville, USA.

Funding

Department of Anesthesiology, University of Virginia School of MedicineNational Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS) K08GM123321 to N.L.
6 · The paper itself

Abstract

introductionPostoperative delirium (POD) is common in older surgical patients and is clinically associated with an increased risk of long-term cognitive decline and dementia; disrupted BDNF signaling and circadian dysregulation are implicated, but their coordinated mechanisms remain unclear.

methodsAged male C57BL/6J mice were exposed to anesthesia, surgery, and intensive care unit-like stress (ASI). Hippocampal neuroplasticity, dendritic morphology, epigenetic regulation, and circadian signaling were assessed using molecular assays, imaging, and protein-protein interaction (PPI) network analysis.

resultsASI reduced brain-derived neurotrophic factor (BDNF)-activity-regulated cytoskeleton-associated protein signaling, dendritic structural complexity, and attention, with accompanying histone hypoacetylation, an increased 5-methylcytosine/5-hydroxymethylcytosine ratio, and disruption of network hubs centered on BDNF and circadian regulators. Suberoylanilide hydroxamic acid mitigated these effects and improved short-term cognitive performance. DISCUSSION: Perioperative stress is associated with an epigenetically repressed, synaptically impaired hippocampal state linked to delirium-like behavior and cognitive vulnerability. Targeting chromatin accessibility and BDNF-circadian coupling with histone deacetylase inhibition may mitigate acute cognitive consequences following surgery.

Indexed as

Brain-Derived Neurotrophic FactorCircadian RhythmDeliriumEpigenesis, GeneticNerve Tissue ProteinsPostoperative ComplicationsAnimalsDisease Models, AnimalHippocampusMaleMiceMice, Inbred C57BLNeuronal PlasticitySignal TransductionVorinostatBdnf protein, mouseBrain-Derived Neurotrophic FactorNerve Tissue ProteinsVorinostatactivity‐regulated cytoskeleton‐associated protein (ARC) proteinbrain‐derived neurotrophic factor (BDNF)‐ tropomyosin receptor kinase B (TrkB) signalingcircadian locomotor output cycles protein kaput (CLOCK) genescognitive‐dementia riskdendritic plasticityepigenetic repressionpostoperative delirium

Identifiers

PMID42298296
PMCPMC13269003

What Socratic holds

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Registered trials

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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.