Evidence map›Paper›PMID 26373814›Full record

ArticleAlcohol and alcoholism (Oxford, Oxfordshire)2015

Differential Contributions of Alcohol and the Nicotine-Derived Nitrosamine Ketone (NNK) to Insulin and Insulin-Like Growth Factor Resistance in the Adolescent Rat Brain.

Ming Tong, Rosa Yu, Chetram Deochand, Suzanne M de la Monte

Open access · bronzeAbstract read
In one paragraph

Article in Alcohol and alcoholism (Oxford, Oxfordshire), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

27 citing papers in PubMed, 31 citations in OpenAlex.

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  15. Independent and Combined Effects of Nicotine or Chronic Tobacco Smoking and HIV on the Brain: A Review of Preclinical and Clinical Studies.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020
    Review
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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

4 authors at 3 institutions in 1 country.

Ming TongDepartment of Medicine, Division of Gastroenterology, and the Liver Research Center, Rhode Island Hospital, Providence, RI, USA Warren Alpert Medical School of Brown University, Providence, RI, USA.
Rosa YuDepartments of Pathology and Neurology, and the Division of Neuropathology, Rhode Island Hospital, Providence, RI, USA.
Chetram DeochandBiotechnology Graduate Program, Brown University, Providence, RI, USA.
Suzanne M de la MonteDepartment of Medicine, Division of Gastroenterology, and the Liver Research Center, Rhode Island Hospital, Providence, RI, USA Warren Alpert Medical School of Brown University, Providence, RI, USA Departments of Pathology and Neurology, and the Division of Neuropathology, Rhode Island Hospital, Providence, RI, USA suzanne_delamonte_md@brown.edu.
Brown University · USProvidence College · USRhode Island Hospital · US

Funding

FASD Inhibition of ASPH-Notch Mediates Adolescent Cerebral White Matter Pathology-Potential Utility of Non-invasive Extracellular Vesicle AssaysR01AA011431 · NIAAA · RHODE ISLAND HOSPITAL (PROVIDENCE, RI) · PI SUZANNE M. DE LA MONTE · 1996 to 2026
$5.4M
Ethanol, IRS-1 Signaling and Neuronal MigrationR37AA011431 · NIAAA · RHODE ISLAND HOSPITAL · PI DE LA MONTE, SUZANNE M. · 2009 to 2018
$3.7M
EFFECTS OF ETHANOL ON INSULIN SIGNALING IN THE BRAINR01AA012908 · NIAAA · RHODE ISLAND HOSPITAL (PROVIDENCE, RI) · PI DE LA MONTE, SUZANNE M. · 2003 to 2013
$3.0M
ETHANOL, INSULIN/IGF SIGNALING AND NEURONAL MIGRATIONR56AA011431 · NIAAA · RHODE ISLAND HOSPITAL · PI DE LA MONTE, SUZANNE M. · 2008 to 2008
$312k
NIAAA NIH HHS AA-11431NIAAA NIH HHS AA-12908
6 · The paper itself

Abstract

aimsSince epidemiologic studies suggest that tobacco smoke toxins, e.g. the nicotine-derived nitrosamine ketone (NNK) tobacco-specific nitrosamine, can be a co-factor in alcohol-related brain disease (ARBD), we examined the independent and additive effects of alcohol and NNK exposures on spatial learning/memory, and brain insulin/IGF signaling, neuronal function and oxidative stress.

methodsAdolescent Long Evans rats were fed liquid diets containing 0 or 26% caloric ethanol for 8 weeks. During weeks 3-8, rats were treated with i.p. NNK (2 mg/kg, 3×/week) or saline. In weeks 7-8, ethanol groups were binge-administered ethanol (2 g/kg; 3×/week). In week 8, at 12 weeks of age, rats were subjected to Morris Water Maze tests. Temporal lobes were used to assess molecular indices of insulin/IGF resistance, oxidative stress and neuronal function.

resultsEthanol and NNK impaired spatial learning, and NNK ± ethanol impaired memory. Linear trend analysis demonstrated worsening performance from control to ethanol, to NNK, and then ethanol + NNK. Ethanol ± NNK, caused brain atrophy, inhibited insulin signaling through the insulin receptor and Akt, activated GSK-3β, increased protein carbonyl and 3-nitrotyrosine, and reduced acetylcholinesterase. NNK increased NTyr. Ethanol + NNK had synergistic stimulatory effects on 8-iso-PGF-2α, inhibitory effects on p-p70S6K, tau and p-tau and trend effects on insulin-like growth factor type 1 (IGF-1) receptor expression and phosphorylation.

conclusionsEthanol, NNK and combined ethanol + NNK exposures that begin in adolescence impair spatial learning and memory in young adults. The ethanol and/or NNK exposures differentially impair insulin/IGF signaling through neuronal growth, survival and plasticity pathways, increase cellular injury and oxidative stress and reduce expression of critical proteins needed for neuronal function.

Indexed as

Insulin ResistanceAcetylcholinesteraseAnimalsAtrophyDinoprostDrug SynergismEthanolGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaInsulinMaleMaze LearningNicotineNitrosaminesOxidative StressPhosphorylation3-nitrotyrosine4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone8-epi-prostaglandin F2alphaAcetylcholinesteraseDinoprostEthanolGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaGsk3b protein, ratInsulinNicotineNitrosaminesReceptor, IGF Type 1Ribosomal Protein S6 Kinases, 70-kDaSomatomedinstau ProteinsTyrosine

Identifiers

PMID26373814
PMCPMC4608623
OpenAlexW1956960444

What OpenQuestion 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 OpenQuestion graph.