Evidence map›Paper›PMID 29336496›Full record

ArticleAlcoholism, clinical and experimental research2018

Donepezil Reverses Dendritic Spine Morphology Adaptations and Fmr1 Epigenetic Modifications in Hippocampus of Adult Rats After Adolescent Alcohol Exposure.

Patrick J Mulholland, Tara L Teppen, Kelsey M Miller, Hannah G Sexton, Subhash C Pandey, H Scott Swartzwelder

Registry-linked trialAbstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04318639 (The Combination of Donepezil and Cognitive Training for Treating Alcohol Use Disorder), which is not on this map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
4.7field-weighted citation impact, top 5% 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.

NCT04318639 phase2 / phase3completednot on this map

The Combination of Donepezil and Cognitive Training for Treating Alcohol Use Disorder

TypeinterventionalSponsorVA Connecticut Healthcare SystemRan2018 to 2019Enrolled15ConditionsAlcohol Use Disorder, Mild Cognitive ImpairmentArmsDonepazil
3 · Its place in the literature

Who cites it

37 citing papers in PubMed, 47 citations in OpenAlex.

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  11. Consequences of adolescent drug use.Translational psychiatry · 2023
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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

6 authors at 2 institutions in 1 country.

Patrick J MulhollandDepartments of Neuroscience and Psychiatry & Behavioral Sciences, Charleston Alcohol Research Center, Charleston, South Carolina.
Tara L TeppenCenter for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago and Jesse Brown VA Medical Center, Chicago, Illinois.
Kelsey M MillerDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center and Durham VA Medical Center, Durham, North Carolina.
Hannah G SextonDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center and Durham VA Medical Center, Durham, North Carolina.
Subhash C PandeyCenter for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago and Jesse Brown VA Medical Center, Chicago, Illinois.
H Scott SwartzwelderDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center and Durham VA Medical Center, Durham, North Carolina.ORCID 0000-0001-5845-1670
Duke Medical Center · USUniversity of Illinois Chicago · US

Funding

Pilot Project Program P50AA022538 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI SUBHASH C. PANDEY · 2015 to 2026
$21.3M
Role of AIE in Epigenetic and Behavioral Changes at AdulthoodU01AA019971 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PANDEY, SUBHASH C. · 2010 to 2024
$5.6M
Supp: Effects of Adolescent Alcohol Exposure on Hippocampal Function in AdulthoodU01AA019925 · NIAAA · DUKE UNIVERSITY · PI SWARTZWELDER, H SCOTT · 2010 to 2024
$5.0M
2/2 NADIA U24 Epigenetic/Molecular CoreU24AA024605 · NIAAA · UNIVERSITY OF ILLINOIS AT CHICAGO · PI PANDEY, SUBHASH C. · 2015 to 2024
$3.6M
1/2 NADIA U24 Dendritic Spine CoreU24AA024603 · NIAAA · MEDICAL UNIVERSITY OF SOUTH CAROLINA · PI MULHOLLAND, PATRICK J. · 2015 to 2019
$841k
NIAAA NIH HHS P50 AA022538NIAAA NIH HHS U01 AA019925NIAAA NIH HHS U01 AA019971NIAAA NIH HHS U24 AA024603NIAAA NIH HHS U24 AA024605
6 · The paper itself

Abstract

backgroundAdolescent intermittent ethanol (AIE) exposure produces persistent impairments in cholinergic and epigenetic signaling and alters markers of synapses in the hippocampal formation, effects that are thought to drive hippocampal dysfunction in adult rodents. Donepezil (Aricept), a cholinesterase inhibitor, is used clinically to ameliorate memory-related cognitive deficits. Given that donepezil also prevents morphological impairment in preclinical models of neuropsychiatric disorders, we investigated the ability of donepezil to reverse morphological and epigenetic adaptations in the hippocampus of adult rats exposed to AIE. Because of the known relationship between dendritic spine density and morphology with the fragile X mental retardation 1 (Fmr1) gene, we also assessed Fmr1 expression and its epigenetic regulation in hippocampus after AIE and donepezil pretreatment.

methodsAdolescent rats were administered intermittent ethanol for 16 days starting on postnatal day 30. Rats were treated with donepezil (2.5 mg/kg) once a day for 4 days starting 20 days after the completion of AIE exposure. Brains were dissected out after the fourth donepezil dose, and spine analysis was completed in dentate gyrus granule neurons. A separate cohort of rats, treated identically, was used for molecular studies.

resultsAIE exposure significantly reduced dendritic spine density and altered morphological characteristics of subclasses of dendritic spines. AIE exposure also increased mRNA levels and H3-K27 acetylation occupancy of the Fmr1 gene in hippocampus. Treatment of AIE-exposed adult rats with donepezil reversed both the dendritic spine adaptations and epigenetic modifications and expression of Fmr1.

conclusionsThese findings indicate that AIE produces long-lasting decreases in dendritic spine density and changes in Fmr1 gene expression in the hippocampal formation, suggesting morphological and epigenetic mechanisms underlying previously reported behavioral deficits after AIE. The reversal of these effects by subchronic, post-AIE donepezil treatment indicates that these AIE effects can be reversed by up-regulating cholinergic function.

Indexed as

AcetylationAgingAnimalsDendritic SpinesDonepezilEpigenesis, GeneticEthanolFragile X Messenger Ribonucleoprotein 1HippocampusMaleRatsDonepezilEthanolFmr1 protein, ratFragile X Messenger Ribonucleoprotein 1Adolescent alcoholDendritic SpinesDonepezilEpigeneticsFmr1HippocampusHistone Acetylation

Identifiers

PMID29336496
PMCPMC5903436
OpenAlexW2782820676

What OpenQuestion holds

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Registered trials

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.