Microglial AGE-Albumin Is Critical in Promoting Alcohol-Induced Neurodegeneration in Rats and Humans
Open accessAbstract
Alcohol is a neurotoxic agent, since long-term heavy ingestion of alcohol can cause various neural diseases including fetal alcohol syndrome, cerebellar degeneracy and alcoholic dementia. However, the molecular mechanisms of alcohol-induced neurotoxicity are still poorly understood despite numerous studies. Thus, we hypothesized that activated microglial cells with elevated AGE-albumin levels play an important role in promoting alcohol-induced neurodegeneration. Our results revealed that microglial activation and neuronal damage were found in the hippocampus and entorhinal cortex following alcohol treatment in a rat model. Increased AGE-albumin synthesis and secretion were also observed in activated microglial cells after alcohol exposure. The expressed levels of receptor for AGE (RAGE)-positive neurons and RAGE-dependent neuronal death were markedly elevated by AGE-albumin through the mitogen activated protein kinase pathway. Treatment with soluble RAGE or AGE inhibitors significantly diminished neuronal damage in the animal model. Furthermore, the levels of activated microglial cells, AGE-albumin and neuronal loss were significantly elevated in human brains from alcoholic indivisuals compared to normal controls. Taken together, our data suggest that increased AGE-albumin from activated microglial cells induces neuronal death, and that efficient regulation of its synthesis and secretion is a therapeutic target for preventing alcohol-induced neurodegeneration.
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Daily alcohol exposure for ten consecutive days instigates microglial activation to synthesize and secrete AGE-albumin adducts in the hippocampus and entorhinal cortex of the rat brain; accumulated AGE-albumin adducts increase RAGE expression and activate MAPK (JNK and p38K)-dependent cell death to promote inflammation, apoptosis, and neuronal damage, attenuated by soluble RAGE and chemical AGE
“Daily alcohol exposure for ten consecutive days also instigated microglial activation to synthesize and secrete AGE-albumin adducts in the hippocampus and entorhinal cortex of the rat brain.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [200]
Soluble RAGE, inhibitors of the RAGE signaling pathway, neutralizing antibodies against RAGE or AA-AGE adduct, and other AGE-degrading compounds have been reported to decrease AGE adduct formation.
“Furthermore, soluble RAGE119,200, inhibitors of the RAGE signaling pathway130,131, neutralizing antibodies against RAGE57 or AA-AGE adduct199, and other AGE-degrading compound(s), such as pyridoxamine and ALT-711200, lipoic acid291, synthetic compounds OPB-9195292, and nitrothiadiazolo[3,2-α]pyrimidines293, have been reported to decrease AGE adduct formation.”
From Advanced glycation end products (AGEs) and other adducts in aging-related diseases and alcohol-mediated tissue injury (2021) · cites this paper as [200]
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Cites
Ramasamy, R., Vannucci, S. J., Yan, S. S. D., Herold, K., Yan, S. F., & Schmidt, A. M. (2005) · Glycobiology · doi:10.1093/glycob/cwi053 · Cited by 834 · see citing works
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 · see citing works
Inflammatory Neurodegeneration and Mechanisms of Microglial Killing of Neurons
Brown, G. C., & Neher, J. J. (2010) · Molecular Neurobiology · doi:10.1007/s12035-010-8105-9 · Cited by 526 · see citing works
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 · see citing works
Binge ethanol exposure decreases neurogenesis in adult rat hippocampus
Nixon, K., & Crews, F. T. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01214.x · Cited by 480 · see citing works
Crews, F. T., Bechara, R. I., Brown, L. A. S., Guidot, D. M., Mandrekar, P., Oak, S. A., Qin, L., Szabó, G., Wheeler, M. D., & Zou, J. (2006) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2006.00084.x · Cited by 414 · see citing works
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 · see citing works
Mechanism of alcohol-induced oxidative stress and neuronal injury
Haorah, J., Ramirez, S. H., Floreani, N. A., Gorantla, S., Morsey, B., & Persidsky, Y. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.08.030 · Cited by 349 · see citing works
Harper, C., & Matsumoto, I. (2005) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2004.06.011 · Cited by 342 · see citing works
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 · see citing works
Qin, L., & Crews, F. T. (2012) · Journal of Neuroinflammation · doi:10.1186/1742-2094-9-5 · Cited by 290 · see citing works
Alcohol, host defence and society
Nelson, S., & Kolls, J. K. (2002) · Nature reviews. Immunology · doi:10.1038/nri744 · Cited by 268 · see citing works
Neurogenesis 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 · see citing works
Binge Ethanol Exposure in Adult Rats Causes Necrotic Cell Death
Obernier, J., Bouldin, T. W., & Crews, F. T. (2002) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2002.tb02573.x · Cited by 258 · see citing works
Marshall, S. A., McClain, J. A., Kelso, M. L., Hopkins, D. M., Pauly, J. R., & Nixon, K. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2012.12.016 · Cited by 243 · see citing works
Ethanol Increases Cytochrome P4502E1 and Induces Oxidative Stress in Astrocytes
Montoliu, C., Sancho‐Tello, M., Azorin, I., Burgal, M., Vallés, S., Renau‐Piqueras, J., & Guerri, C. (1995) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1995.65062561.x · Cited by 218 · see citing works
CCL2/MCP-1 modulation of microglial activation and proliferation
Hinojosa, A. E., García‐Bueno, B., Leza, J. C., & Madrigal, J. L. M. (2011) · Journal of Neuroinflammation · doi:10.1186/1742-2094-8-77 · Cited by 195 · see citing works
Adolescent binge alcohol exposure induces long-lasting partial activation of microglia
McClain, J. A., Morris, S. A. V., Deeny, M. A., Marshall, S. A., Hayes, D. M., Kiser, Z. M., & Nixon, K. (2011) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2011.01.006 · Cited by 189 · see citing works
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 184 · see citing works
Jin, M., Ande, A., Kumar, A., & Kumar, S. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.78 · Cited by 181 · see citing works
Nagai, A., Nakagawa, E., Hatori, K., Choi, H. B., McLarnon, J. G., Lee, M. A., & Kim, S. U. (2001) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0437 · Cited by 153 · see citing works
Self-citationZhao, Y., Wang, F., Fan, Y., Ping, G.-F., Yang, J., & Wu, C. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.08.052 · Cited by 153 · see citing works
Yan, S. F., Yan, S. D., Ramasamy, R., & Schmidt, A. M. (2009) · Annals of Medicine · doi:10.1080/07853890902806576 · Cited by 133 · see citing works
Vetreno, R. P., Qin, L., & Crews, F. T. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.07.002 · Cited by 132 · see citing works
Vilpoux, C., Warnault, V., Pierrefiche, O., Daoust, M., & Naassila, M. (2009) · Alcoholism: Clinical and Experimental Research · doi:10.1111/j.1530-0277.2009.00916.x · Cited by 131 · see citing works
Nixon, K., Kim, D. H., Potts, E. N., He, J., & Crews, F. T. (2008) · Neurobiology of Disease · doi:10.1016/j.nbd.2008.04.009 · Cited by 117 · see citing works
Shi, L., Yu, X., Yang, H., & Wu, X. (2013) · PLoS ONE · doi:10.1371/journal.pone.0066781 · Cited by 105 · see citing works
Human Microglial Cells Synthesize Albumin in BrainPreprint
Ahn, S., Byun, K., Cho, K., Kim, J. Y., Yoo, J. S., Kim, D., Paek, S. H., Kim, S. U., Simpson, R. J., & Lee, B. (2008) · Nature Precedings · doi:10.1371/journal.pone.0002829 · Cited by 87 · see citing works
Self-citationInduction of Neuronal Death by Microglial AGE-Albumin: Implications for Alzheimer’s Disease
Byun, K., Bayarsaikhan, E., Kim, D., Kim, C. Y., Mook-Jung, I., Paek, S. H., Kim, S. U., Yamamoto, T., Won, M.-H., Song, B.-J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037917 · Cited by 75 · see citing works
Self-citationJeanblanc, J., Logrip, M. L., Janak, P. H., & Dorit Ron, A. (2012) · European Journal of Neuroscience · doi:10.1111/ejn.12067 · Cited by 72 · see citing works
Role of Microglia in Ethanol’s Apoptotic Action on Hypothalamic Neuronal Cells in Primary Cultures
Boyadjieva, N. I., & Sarkar, D. K. (2010) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2010.01271.x · Cited by 69 · see citing works
Determining the Threshold for Alcohol‐Induced Brain Damage: New Evidence with Gliosis Markers
Hayes, D. M., Deeny, M. A., Shaner, C. A., & Nixon, K. (2013) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2012.01955.x · Cited by 68 · see citing works
Boyadjieva, N. I., & Sarkar, D. K. (2012) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2012.01889.x · Cited by 64 · see citing works
Preinjury alcohol exposure attenuates the neuroinflammatory response to traumatic brain injury
Goodman, M. D., Makley, A. T., Campion, E. M., et al. (2013) · Journal of Surgical Research · doi:10.1016/j.jss.2013.04.058 · Cited by 60 · see citing works
Molecular Regulation of Acute Ethanol-Induced Neuron Apoptosis
Akhtar, L. N., Klocke, B. J., & Roth, K. A. (2005) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/64.6.490 · Cited by 58 · see citing works
Ethanol selectively modulates inflammatory activation signaling of brain microglia
Lee, H., Jeong, J., Son, E., Mosa, A., Cho, G. J., Choi, W. S., Ha, J., Kim, I. K., Lee, M., Kim, C.-Y., et al. (2004) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2004.07.008 · Cited by 43 · see citing works
Sullivan, E. V., & Zahr, N. M. (2008) · Experimental Neurology · doi:10.1016/j.expneurol.2008.05.016 · Cited by 40 · see citing works
Biological Studies on Alcohol-Induced Neuronal Damage
Tateno, M., & Saito, T. (2008) · Psychiatry Investigation · doi:10.4306/pi.2008.5.1.21 · Cited by 39 · see citing works
Proteomics Approach in the Study of the Pathophysiology of Alcohol-Related Brain Damage
Matsumoto, I. (2009) · Alcohol and Alcoholism · doi:10.1093/alcalc/agn104 · Cited by 38 · see citing works
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Research works printed but not linked: 1
- [34]Ahn SM, Byun K, Cho K, Kim JY, Yoo JS, et al (2008) Human microglial cells synthesize albumin in brain. PLoS One 3: e2829. 18665237 PMC2483733
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Self-citationByun, K., Yoo, Y., Son, M., Lee, J., Jeong, G.-B., Park, Y. M., Salekdeh, G. H., & Lee, B. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.030 · Cited by 357 · see citing works
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Kuzan, A. (2021) · Biomedical Reports · doi:10.3892/br.2021.1422 · Cited by 151 · see citing works
Song, B.-J., Akbar, M., Abdelmegeed, M. A., Byun, K., Lee, B., Yoon, S. K., & Hardwick, J. P. (2014) · Redox Biology · doi:10.1016/j.redox.2014.10.004 · Cited by 123 · see citing works
“Consistent with this report, elevated amounts of AGE-albumin adduct, produced by activated microglial cells, were found in alcohol-exposed rat brains and post-mortem brains from human alcoholic individuals compared to those of healthy normal counterparts [199].”
BackgroundSelf-citation
- Authors
- Byun, K., Bayarsaikhan, D., Bayarsaikhan, E., Son, M., Oh, S., Lee, J., Son, H.-I., Won, M.-H., Kim, S. U., Song, B.-J., & Lee, B.
- Affiliations
- Gachon University (KR)
- University of California, Berkeley (US)
- Kangwon National University (KR)
- University of British Columbia (CA)
- National Institutes of Health (US)
- Corresponding author
- Song, Byoung-Joon
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2014-08-20
- Volume
- 9
- Issue
- 8
- Pages
- e104699
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC4139297
- OpenAlex
- W2052645547
- Cited by
- 28
- References
- 39
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 2 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 3 · 2015: 1 · 2014: 1
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- National Research Foundation
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
- Keywords
- advanced glycation end products, microglial activation, receptor for advanced glycation end products, RAGE, neuronal cell death, hippocampus, entorhinal cortex, MAPK signaling, soluble RAGE, AGE inhibitors, alcohol-related dementia, neuroinflammation
- MeSH terms
- Adult, Aged, Albumins, Ethanol, Alcoholism, Animals, Brain, Humans, Male, Middle Aged, Nerve Degeneration, Neurons, Microglia, Rats
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