ArticleJournal of diabetes and related disorders2016
Differential Effects of 3rd Trimester-Equivalent Binge Ethanol and Tobacco-Specific Nitrosamine Ketone Exposures on Brain Insulin Signaling in Adolescence.
Article in Journal of diabetes and related disorders, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
What it found
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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.
The trial behind it
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Who cites it
12 citing papers in PubMed, 13 citations in OpenAlex.
- Dietary Soy Preserves Cognitive Function in Experimental Fetal Alcohol Spectrum Disorder: Role of Increased Signaling through Notch and Gonadotropin Releasing Hormone Networks.Journal of behavioral and brain science · 2025Article
- Review
- Brain and Serum Membrane Vesicle (Exosome) Profiles in Experimental Alcohol-Related Brain Degeneration: Forging the Path to Non-Invasive Liquid Biopsy Diagnostics.Journal of molecular pathology · 2024Article
- Early-Stage Moderate Alcohol Feeding Dysregulates Insulin-Related Metabolic Hormone Expression in the Brain: Potential Links to Neurodegeneration Including Alzheimer's Disease.Journal of Alzheimer's disease reports · 2024Article
- Dietary soy prevents fetal demise, intrauterine growth restriction, craniofacial dysmorphic features, and impairments in placentation linked to gestational alcohol exposure: Pivotal role of insulin and insulin-like growth factor signaling networks.Alcohol (Fayetteville, N.Y.) · 2023Article
- Differential Early Mechanistic Frontal Lobe Responses to Choline Chloride and Soy Isoflavones in an Experimental Model of Fetal Alcohol Spectrum Disorder.International journal of molecular sciences · 2023Article
- Agent Orange Causes Metabolic Dysfunction and Molecular Pathology Reminiscent of Alzheimer's Disease.Journal of Alzheimer's disease reports · 2023Article
- Differential rescue effects of choline chloride and soy isolate on metabolic dysfunction in immature central nervous system neurons: Relevance to fetal alcohol spectrum disorder.Diabetes management (London, England) · 2023Article
- Dietary Soy Prevents Alcohol-Mediated Neurocognitive Dysfunction and Associated Impairments in Brain Insulin Pathway Signaling in an Adolescent Rat Model.Biomolecules · 2022Article
- Imaging mass spectrometry of frontal white matter lipid changes in human alcoholics.Alcohol (Fayetteville, N.Y.) · 2018Article
- Progressive white matter atrophy with altered lipid profiles is partially reversed by short-term abstinence in an experimental model of alcohol-related neurodegeneration.Alcohol (Fayetteville, N.Y.) · 2017Article
- Ethanol-Induced White Matter Atrophy Is Associated with Impaired Expression of Aspartyl-Asparaginyl-Journal of drug and alcohol research · 2017Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundFetal alcohol spectrum disorder (FASD) is associated with impairments in insulin and insulin-like growth factor (IGF) signaling through Akt pathways and altered expression of neuro-glial proteins needed for structural and functional integrity of the brain. However, alcohol abuse correlates with smoking, and tobacco smoke contains 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which like other nitrosamines, impairs insulin and IGF signaling. HYPOTHESIS: NNK exposure can serve as a co-factor in mediating long-term neuro-developmental abnormalities associated with FASD.
designLong Evans rat pups were IP administered ethanol (2 g/kg) on postnatal days (P) 2, 4, 6 and/or NNK (2 mg/kg) on P3, P5, and P7, simulating third trimester human exposures. Temporal lobes from P30 rats (young adolescent) were used to measure signaling through the insulin/IGF-1/Akt pathways by multiplex ELISAs, and expression of neuroglial proteins by duplex ELISAs.
resultsEthanol, NNK, and ethanol + NNK exposures significantly inhibited insulin receptor tyrosine phosphorylation, and IRS-1 and myelin-associated glycoprotein expression. However, the major long-term adverse effects on Akt pathway downstream signaling and its targeted proteins including choline acetyltransferase, Tau, pTau, ubiquitin, and aspartate-β-hydroxylase were due to NNK rather than ethanol.
conclusionAlcohol and tobacco exposures can both contribute to long-term brain abnormalities currently regarded fetal ethanol effects. However, the findings suggest that many of the adverse effects on brain function are attributable to smoking, including impairments in signaling through survival and metabolic pathways, and altered expression of genes that regulate myelin synthesis, maturation and integrity and synaptic plasticity. Therefore, public health measures should address both substances of abuse to prevent "FASD".
Indexed as
Identifiers
29242853PMC5726776W2749215898What OpenQuestion holds
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.