Evidence map›Paper›PMID 34420963›Full record

ArticleJournal of Alzheimer's disease : JAD2021

Gene-Specific DNA Methylation Linked to Postoperative Cognitive Dysfunction in Apolipoprotein E3 and E4 Mice.

Katie J Schenning, Sarah Holden, Brett A Davis, Amelia Mulford, Kimberly A Nevonen, Joseph F Quinn, Jacob Raber, Lucia Carbone, Nabil J Alkayed

Open access · greenAbstract read
In one paragraph

Article in Journal of Alzheimer's disease : JAD, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
1.2field-weighted citation impact, top 24% 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

7 citing papers in PubMed, 12 citations in OpenAlex.

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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

9 authors at 2 institutions in 1 country.

Katie J SchenningDepartment of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
Sarah HoldenDepartment of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
Brett A DavisDepartment of Medicine, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
Amelia MulfordDepartment of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
Kimberly A NevonenDepartment of Medicine, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
Joseph F QuinnDepartment of Neurology, Oregon Health & Science University, Portland, OR, USA.
Jacob RaberDepartment of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA.
Lucia CarboneDepartment of Medicine, Knight Cardiovascular Institute, Oregon Health & Science University, Portland, OR, USA.
Nabil J AlkayedDepartment of Anesthesiology & Perioperative Medicine, Oregon Health & Science University, Portland, OR, USA.
Oregon Health & Science University · USOregon National Primate Research Center · US

Funding

Research Education ComponentP30AG066518 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI JOSEPH F QUINN · 2020 to 2026
$28.6M
Scholars in Women's Health Research Across the LifespanK12HD043488 · NICHD · OREGON HEALTH & SCIENCE UNIVERSITY · PI MYATT, LESLIE · 2002 to 2023
$10.4M
Neuroinflammatory Mechanisms of Vascular Cognitive ImpairmentRF1AG058273 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI ALKAYED, NABIL J · 2017 to 2023
$4.2M
Effects of apoE Isoform, Sex and Diet on Insulin Regulation in BrainRF1AG059088 · NIA · SEATTLE INST FOR BIOMEDICAL/CLINICAL RES · PI BANKS, WILLIAM A, RABER, JACOB · 2018 to 2020
$2.5M
Determinants of vulnerability and recovery after trauma to the developing brainR01NS077767 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI NOBLE, LINDA J. · 2012 to 2016
$1.7M
Identification of markers of early epigenetic dysregulation in Alzheimer's diseaseR21AG065681 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI CARBONE, LUCIA · 2020 to 2020
$424k
Impact of Second-Hand Smoke on Brain Metabolism and Cognition in MiceR21ES027943 · NIEHS · OREGON HEALTH & SCIENCE UNIVERSITY · PI KISBY, GLEN E, RABER, JACOB · 2018 to 2019
$397k
The role of Alzheimer's risk factors in cognitive decline after spine surgeryR03AG056462 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI SCHENNING, KATIE JO · 2018 to 2019
$231k
NIA NIH HHS P30 AG066518NIA NIH HHS R03 AG056462NIA NIH HHS R21 AG065681NIA NIH HHS RF1 AG058273NIA NIH HHS RF1 AG059088NICHD NIH HHS K12 HD043488NIEHS NIH HHS R21 ES027943NINDS NIH HHS R01 NS077767
6 · The paper itself

Abstract

backgroundGeriatric surgical patients are at higher risk of developing postoperative neurocognitive disorders (NCD) than younger patients. The specific mechanisms underlying postoperative NCD remain unknown, but they have been linked to genetic risk factors, such as the presence of APOE4, compared to APOE3, and epigenetic modifications caused by exposure to anesthesia and surgery.

objectiveTo test the hypothesis that compared to E3 mice, E4 mice exhibit a more pronounced postoperative cognitive impairment associated with differential DNA methylation in brain regions linked to learning and memory.

methods16-month-old humanized apolipoprotein-E targeted replacement mice bearing E3 or E4 were subjected to surgery (laparotomy) under general isoflurane anesthesia or sham. Postoperative behavioral testing and genome-wide DNA methylation were performed.

resultsExposure to surgery and anesthesia impaired cognition in aged E3, but not E4 mice, likely due to the already lower cognitive performance of E4 prior to surgery. Cognitive impairment in E3 mice was associated with hypermethylation of specific genes, including genes in the Ephrin pathway implicated in synaptic plasticity and learning in adults and has been linked to Alzheimer's disease. Other genes, such as the Scratch Family Transcriptional Repressor 2, were altered after surgery and anesthesia in both the E3 and E4 mice.

conclusionOur findings suggest that the neurocognitive and behavioral effects of surgery and anesthesia depend on baseline neurocognitive status and are associated with APOE isoform-dependent epigenetic modifications of specific genes and pathways involved in memory and learning.

Indexed as

DNA MethylationMice, TransgenicPostoperative Cognitive ComplicationsAlzheimer DiseaseAnimalsApolipoprotein E3Apolipoprotein E4BrainCognitive DysfunctionDisease Models, AnimalHumansLearningMaleMiceApolipoprotein E3Apolipoprotein E4Alzheimer’s diseaseanesthesiaapolipoprotein E4behaviorDNA methylationephrinsepigenomicshippocampuspostoperative cognitive complicationssurgery

Identifiers

PMID34420963
PMCPMC8801332
OpenAlexW3196004100

What OpenQuestion holds

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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 OpenQuestion graph.