The DOI matches its Crossref record; 65 of the 66 references it cites were found in a registry or an index.
Adolescent binge drinking increases expression of the danger signal receptor agonist HMGB1 and toll-like receptors in the adult prefrontal cortex
Open accessAbstract
Adolescence is a critical developmental stage of life during which the prefrontal cortex (PFC) matures, and binge drinking and alcohol abuse are common. Recent studies have found that ethanol increases neuroinflammation via upregulated high-mobility group box 1 (HMGB1) signaling through Toll-like receptors (TLRs). HMGB1/TLR 'danger signaling' induces multiple brain innate immune genes that could alter brain function. To determine whether adolescent binge drinking persistently increases innate immune gene expression in the PFC, rats (P25-P55) were exposed to adolescent intermittent ethanol (AIE [5.0 g/kg, 2-day on/2-day off schedule]). On P56, HMGB1/TLR danger signaling was assessed using immunohistochemistry (i.e., +immunoreactivity [+IR]). In a separate group of subjects, spatial and reversal learning on the Barnes maze was assessed in early adulthood (P64-P75), and HMGB1/TLR danger signaling was measured using immunohistochemistry for +IR and RT-PCR for mRNA in adulthood (P80). Immunohistochemical assessment at P56 and 24 days later at P80 revealed increased frontal cortical HMGB1, TLR4, and TLR3 in the AIE-treated rats. Adolescent intermittent ethanol treatment did not alter adult spatial learning on the Barnes maze, but did cause reversal learning deficits and increased perseverative behavior. Barnes maze deficits correlated with the expression of danger signal receptors in the PFC. Taken together, these findings provide evidence that adolescent binge drinking leads to persistent upregulation of innate immune danger signaling in the adult PFC that correlates with adult neurocognitive dysfunction.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“They found that previous adolescent ethanol exposure did not impact acquisition of the Barnes maze but did disrupt reversal learning in adulthood, with alcohol exposed mice exhibiting longer latencies to find the new escape hole and spending a longer time in the previously learned hole location when compared to controls.”
From The long-term cognitive consequences of adolescent exposure to recreational drugs of abuse (2018) · cites this paper as Vetreno and Crews 2012
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Although there is evidence for persistent neurological and cognitive deficits in HC function, it is important to note that certain aspects of HC-dependent learning and memory, such as spatial learning and memory, were not impacted following adolescent exposure (Coleman et al. 2011; Vetreno and Crews 2012) but were in adults (Cippitelli et al. 2010).”
From The long-term cognitive consequences of adolescent exposure to recreational drugs of abuse (2018) · cites this paper as Vetreno and Crews 2012
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
The Rat Brain in Stereotaxic Coordinates
Paxinos, G., & Watson, C. (1983) · Elsevier eBooks · doi:10.1016/c2009-0-63235-9 · Cited by 28,585
From inflammation to sickness and depression: when the immune system subjugates the brain
Dantzer, R., O'Connor, J. C., Freund, G. G., Johnson, R. W., & Kelley, K. W. (2008) · Nature Reviews Neuroscience · doi:10.1038/nrn2297 · Cited by 7,395
Monitoring the Future: National Results on Adolescent Drug Use: Overview of Key Findings
Johnston, L. D., O’Malley, P. M., Bachman, J. G., & Schulenberg, J. E. (2003) · FOCUS The Journal of Lifelong Learning in Psychiatry · doi:10.1037/e560352009-001 · Cited by 6,930
Systemic LPS causes chronic neuroinflammation and progressive neurodegeneration
Qin, L., Wu, X., Block, M. L., Liu, Y., Breese, G. R., Hong, J., Knapp, D. J., & Crews, F. T. (2007) · Glia · doi:10.1002/glia.20467 · Cited by 2,144
Self-citationPark, J. S., Svetkauskaite, D., He, Q., Kim, J., Strassheim, D., Ishizaka, A., & Abraham, E. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306793200 · Cited by 1,582
Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism
Block, M. L., & Hong, J.-S. (2005) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2005.06.004 · Cited by 1,557
Immune modulation of learning, memory, neural plasticity and neurogenesis
Yirmiya, R., & Goshen, I. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2010.10.015 · Cited by 1,483
HMGB1 and RAGE in Inflammation and Cancer
Sims, G. P., Rowe, D. C., Rietdijk, S. T., Herbst, R., & Coyle, A. J. (2010) · Annual Review of Immunology · doi:10.1146/annurev.immunol.021908.132603 · Cited by 1,436
Correlates of college student binge drinking.
Wechsler, H., Dowdall, G. W., Davenport, A. E., & Castillo, S. (1995) · American Journal of Public Health · doi:10.2105/ajph.85.7.921 · Cited by 787
Pivotal role of TLR4 receptors in alcohol-induced neuroinflammation and brain damage
Alfonso-Loeches, S., Pascual-Lucas, M., Blanco, A. M., Sanchez-Vera, I., & Guerri, C. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.0976-10.2010 · Cited by 579
Neurocognitive Functioning of Adolescents: Effects of Protracted Alcohol Use
Brown, S. A., Tapert, S. F., Granholm, E. L., & Delis, D. C. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2000.tb04586.x · Cited by 575
Qin, L., He, J., Hanes, R. N., Pluzarev, O., Hong, J.-S., & Crews, F. T. (2008) · Journal of Neuroinflammation · doi:10.1186/1742-2094-5-10 · Cited by 532
Self-citationImmunogenic cell death, DAMPs and anticancer therapeutics: An emerging amalgamation
Garg, A. D., Nowis, D., Gołąb, J., Vandenabeele, P., Krysko, D. V., & Agostinis, P. (2009) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2009.08.003 · Cited by 517
Increased MCP-1 and microglia in various regions of the human alcoholic brain
He, J., & Crews, F. T. (2007) · Experimental Neurology · doi:10.1016/j.expneurol.2007.11.017 · Cited by 516
Self-citationCrews, F. T., Braun, C. J., Hoplight, B., Switzer, R. C., & Knapp, D. J. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2000.tb01973.x · Cited by 504
Self-citationToll-like receptors in health and disease in the brain: mechanisms and therapeutic potential
Hanke, M. L., & Kielian, T. (2011) · Clinical Science · doi:10.1042/cs20110164 · Cited by 498
Toll-like receptors in neurodegeneration
Okun, E., Griffioen, K. J. S., Lathia, J. D., Tang, S., Mattson, M. P., & Arumugam, T. V. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2008.09.001 · Cited by 444
Pascual, M., Blanco, A. M., Cauli, O., Miñarro, J., & Guerri, C. (2007) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.05298.x · Cited by 385
Critical role of TLR4 response in the activation of microglia induced by ethanol
Fernandez-Lizarbe, S., Pascual, M., & Guerri, C. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0803590 · Cited by 373
MacFabe, D. F., Cain, N. E., Boon, F., Ossenkopp, K.-P., & Cain, D. P. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.10.005 · Cited by 365
Vezzani, A., Maroso, M., Balosso, S., Sanchez, M.-A., & Bartfai, T. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.03.018 · Cited by 362
Paull, T. T., Haykinson, M. J., & Johnson, R. C. (1993) · Genes & Development · doi:10.1101/gad.7.8.1521 · Cited by 326
Early drinking onset and its association with alcohol use and problem behavior in late adolescence
Gruber, E., DiClemente, R. J., Anderson, M. M., & Lodico, M. (1996) · Preventive Medicine · doi:10.1006/pmed.1996.0059 · Cited by 324 · cited 1×
“In addition to the involvement of danger signal receptors in neuroinflammation, these receptors also modulate cognitive and emotive functioning (Dantzer et al., 2008; Okun et al., 2010; Hanke and Kielian, 2011; Yirmiya and Goshen, 2011).”
BackgroundThe Role of Orbitofrontal Cortex in Drug Addiction: A Review of Preclinical Studies
Schoenbaum, G. M., & Shaham, Y. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.06.003 · Cited by 323
Nizri, E., Irony-Tur-Sinai, M., Lory, O., Orr‐Urtreger, A., Lavi, E., & Brenner, T. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0902212 · Cited by 315
Induction of innate immune genes in brain create the neurobiology of addiction
Crews, F. T., Zou, J., & Qin, L. (2011) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2011.03.003 · Cited by 313
Self-citationContributions of peripheral inflammation to seizure susceptibility: Cytokines and brain excitability
Riazi, K., Galic, M. A., & Pittman, Q. J. (2009) · Epilepsy Research · doi:10.1016/j.eplepsyres.2009.09.004 · Cited by 310
Crews, F. T., Qin, L., Sheedy, D. L., Vetreno, R. P., & Zou, J. (2012) · Biological Psychiatry · doi:10.1016/j.biopsych.2012.09.030 · Cited by 305
Self-citationQin, L., & Crews, F. T. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-5 · Cited by 290
Self-citationNeurogenesis in adolescent brain is potently inhibited by ethanol
Crews, F. T., Mdzinarishvili, A., Kim, D., He, J., & Nixon, K. (2006) · Neuroscience · doi:10.1016/j.neuroscience.2005.08.090 · Cited by 265
Self-citationCognitive deficits and CNS damage after a 4-day binge ethanol exposure in rats
Obernier, J., White, A. M., Swartzwelder, H. S., & Crews, F. T. (2002) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)00715-3 · Cited by 261
Self-citationBlanco, A. M., Vallés, S. L., Pascual, M., & Guerri, C. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.6893 · Cited by 258
HMG1 and 2: architectural DNA-binding proteins
Thomas, J. O. (2001) · Biochemical Society Transactions · doi:10.1042/bst0290395 · Cited by 257
Jurgens, H. A., Amancherla, K., & Johnson, R. W. (2012) · The Journal of Neuroscience · doi:10.1523/jneurosci.6389-11.2012 · Cited by 243
Hanson, K. L., Medina, K. L., Padula, C. B., Tapert, S. F., & Brown, S. A. (2011) · Journal of Child & Adolescent Substance Abuse · doi:10.1080/1067828x.2011.555272 · Cited by 235
Toll-like receptor 3 inhibits memory retention and constrains adult hippocampal neurogenesis
Okun, E., Griffioen, K. J. S., Barak, B., Roberts, N. J., Castro, K., Pita, M. A., Cheng, A., Mughal, M. R., Wan, R., Ashery, U., et al. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005807107 · Cited by 207
O’Malley, P. M., Johnston, L. D., & Bachman, J. G. (2000) · Choice Reviews Online · doi:10.5860/choice.37-3066 · Cited by 201
Coleman Jr, L. G., He, J., Lee, J., Styner, M., & Crews, F. T. (2011) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2010.01385.x · Cited by 197
Self-citationHMGB1 in Development and Diseases of the Central Nervous System
Fang, P., Schachner, M., & Shen, Y.-Q. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8264-y · Cited by 193
BHT Blocks NF‐κB activation and Ethanol‐Induced Brain Damage
Crews, F. T., Nixon, K., Kim, D., Joseph, J. A., Shukitt‐Hale, B., Qin, L., & Zou, J. (2006) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2006.00239.x · Cited by 185
Self-citationWindle, M. T. (1999) · Sage eBooks · doi:10.4135/9781452233734 · Cited by 184
Regulation of cell migration by amphoterin
Fages, C., Nolo, R. M., Huttunen, H. J., Eskelinen, E., & Rauvala, H. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.4.611 · Cited by 166
Zou, J., & Crews, F. T. (2006) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-006-9045-9 · Cited by 165
Self-citationExercise reverses ethanol inhibition of neural stem cell proliferation
Crews, F. T., Nixon, K., & Wilkie, M. E. (2004) · Alcohol · doi:10.1016/j.alcohol.2004.04.005 · Cited by 165
Self-citationZou, J., & Crews, F. T. (2010) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2010.01150.x · Cited by 159
Self-citationNeural substrates of cognitive inflexibility after chronic cocaine exposure
Stalnaker, T. A., Takahashi, Y. K., Roesch, M. R., & Schoenbaum, G. M. (2008) · Neuropharmacology · doi:10.1016/j.neuropharm.2008.07.019 · Cited by 156
Tapert, S., & Brown, S. A. (2000) · Addiction · doi:10.1046/j.1360-0443.2000.95710436.x · Cited by 146
Comparative neuropsychology and Korsakoff's syndrome. I—Spatial and visual reversal learning
Oscar‐Berman, M., & Zola-Morgan, S. M. (1980) · Neuropsychologia · doi:10.1016/0028-3932(80)90152-9 · Cited by 137
Nizri, E., Irony-Tur-Sinai, M., Faranesh, N., Lavon, I., Lavi, E., Weinstock, M., & Brenner, T. (2008) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2008.06.018 · Cited by 134
Trudler, D., Farfara, D., & Frenkel, D. (2010) · Mediators of Inflammation · doi:10.1155/2010/497987 · Cited by 126
Knapp, D. J., & Crews, F. T. (1999) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.1999.tb04165.x · Cited by 121
Self-citationRauvala, H., & Rouhiainen, A. (2009) · Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms · doi:10.1016/j.bbagrm.2009.11.012 · Cited by 106
White, H. R., Marmorstein, N. R., Crews, F. T., Bates, M. E., Mun, E.-Y., & Loeber, R. (2011) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2010.01345.x · Cited by 92
Self-citationBadanich, K. A., Becker, H. C., & Woodward, J. J. (2011) · Behavioral Neuroscience · doi:10.1037/a0025922 · Cited by 89
Ehlers, C. L., Criado, J. R., Wills, D. N., Liu, W., & Crews, F. T. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.10.011 · Cited by 79
Self-citationHigh mobility group box 1 (HMGB1)
Yang, H., & Tracey, K. J. (2005) · Critical Care Medicine · doi:10.1097/01.ccm.0000187005.81616.a9 · Cited by 76
Spatial and visual learning deficits in Alzheimer's and Parkinson's disease
Freedman, M., & Oscar‐Berman, M. (1989) · Brain and Cognition · doi:10.1016/0278-2626(89)90009-2 · Cited by 69
High Mobility Group Box-1 (HMGB1; Amphoterin) Is Required for Zebrafish Brain Development
Zhao, X., Kuja‐Panula, J., Rouhiainen, A., Chen, Y., Panula, P., & Rauvala, H. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.223834 · Cited by 69
Cheng, G., Whitehead, S. N., Hachinski, V., & Cechetto, D. F. (2006) · Neurobiology of Disease · doi:10.1016/j.nbd.2006.02.008 · Cited by 68
The Role of HMGB1/RAGE in Inflammatory Cardiomyopathy
Volz, H. C., Kaya, Z., Katus, H. A., & Andrassy, M. (2010) · Seminars in Thrombosis and Hemostasis · doi:10.1055/s-0030-1251503 · Cited by 67
Targeting HMGB1 TLR4 signaling as a novel approach to treatment of cerebral ischemia
Yang, Q.-W. (2010) · Frontiers in Bioscience · doi:10.2741/s119 · Cited by 55 · cited 2×
“TLR4 receptors are critically involved in the activation of monocytes and microglia (Fernandez-Lizarbe et al., 2009; Yang et al., 2010), which is consistent with microglia initiating neuroimmune responses following ethanol exposure (Block and Hong, 2005; Crews et al.”
BackgroundATP‐P2X7receptor signaling controls basal and TNFα‐stimulated glial cell proliferation
Zou, J., Vetreno, R. P., & Crews, F. T. (2012) · Glia · doi:10.1002/glia.22302 · Cited by 55
Self-citationAnxiolytic potential of sulpiride, clozapine and derivatives in the open-field test
Bruhwyler, J., Chleide, E. M. G., Liégeois, J.-F., Delarge, J., & MERCIER, M. G. A. (1990) · Pharmacology Biochemistry and Behavior · doi:10.1016/0091-3057(90)90125-2 · Cited by 53
Delay discrimination and reversal eyeblink classical conditioning in abstinent chronic alcoholics.
Fortier, C. B., Steffen, E. M., Lafleche, G., Venne, J. R., Disterhoft, J. F., & McGlinchey, R. E. (2008) · Neuropsychology · doi:10.1037/0894-4105.22.2.196 · Cited by 50
Kosaki, Y., & Watanabe, S. (2011) · Behavioural Brain Research · doi:10.1016/j.bbr.2011.10.039 · Cited by 45
Flagged first, then by citations
1 of the 66 references couldn’t be matched to a known paper.
Research works printed but not linked: 2
- Crews FT, Qin L, Sheedy D, Vetreno RP, Zou J (in press) HMGB1/TLR receptor danger signaling increases brain neuroimmune activation in alcohol dependence. Biol Psychiatry.
- Johnston, 2009, Vol. 1
Cited by
Sorted by citations
Adolescent alcohol exposure: Are there separable vulnerable periods within adolescence?
SPEAR, L. P. (2015) · Physiology & Behavior · doi:10.1016/j.physbeh.2015.01.027 · Cited by 383
Adolescent Alcohol Exposure Persistently Impacts Adult Neurobiology and Behavior
Crews, F. T., Vetreno, R. P., Broadwater, M., & Robinson, D. L. (2016) · Pharmacological Reviews · doi:10.1124/pr.115.012138 · Cited by 356
Self-citationThe role of neuroimmune signaling in alcoholism
Crews, F. T., Lawrimore, C. J., Walter, T. J., & Coleman, L. G. (2017) · Neuropharmacology · doi:10.1016/j.neuropharm.2017.01.031 · Cited by 321
Self-citationMechanisms of neuroimmune gene induction in alcoholism
Crews, F. T., & Vetreno, R. P. (2016) · Psychopharmacology · doi:10.1007/s00213-015-3906-1 · Cited by 232
Self-citationNeuroimmune Function and the Consequences of Alcohol Exposure
Crews, F. T. (2015) · Alcohol research · doi:10.35946/arcr.v37.2.15 · Cited by 203
Self-citation
Metadata
- Authors
- Vetreno, R. P., & Crews, F. T.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Vetreno, R.P.
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 226
- Pages
- 475-488
- ISSN
- 0306-4522 (ISSN-L)
- PMC
- PMC3740555
- OpenAlex
- W2089714619
- Cited by
- 183
- References
- 66
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 13 · 2023: 8 · 2022: 16 · 2021: 23 · 2020: 14 · 2019: 14 · 2018: 9 · 2017: 20 · 2016: 15 · 2015: 15 · 2014: 11 · 2013: 8
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- UNC Libraries
- Funders
- Center for Alcohol Studies
- National Institutes of Health (AA-11605, AA007573, AA019767)
- National Institute on Alcohol Abuse and Alcoholism (P50AA011605, AA 11605, U24AA020022, U01AA020023, AA020023, L40 AA021590, AA021040, AA 007573, F32AA021040, AA020022, AA020024, U24AA020024, U54AA019767, AA019767, P60AA011605, T32AA007573)
- Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- adolescent binge drinking, prefrontal cortex, HMGB1, danger signaling, TLR4, TLR3, neuroinflammation, innate immunity, spatial learning, perseveration, neurocognitive impairment, alcohol abuse
- MeSH terms
- Adolescent, Animals, Cognition Disorders, Female, Fluorescent Antibody Technique, Humans, Image Processing, Computer-Assisted, Immunohistochemistry, Reversal Learning, Rats, Wistar, Prefrontal Cortex, Microscopy, Confocal, Maze Learning, HMGB1 Protein, Toll-Like Receptors, Toll-Like Receptor 3, Toll-Like Receptor 4, Rats, Real-Time Polymerase Chain Reaction, Binge Drinking
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
