Ethanol Induces Neuroinflammation in a Chronic Plus Binge Mouse Model of Alcohol Use Disorder via TLR4 and MyD88-Dependent Signaling Article Swipe
Kalee N. Holloway
,
James C. Douglas
,
Tonya Rafferty
,
Cynthia J.M. Kane
,
Paul D. Drew
·
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/cells12162109
YOU?
·
· 2023
· Open Access
·
· DOI: https://doi.org/10.3390/cells12162109
Ethanol induces neuroinflammation, which is believed to contribute to the pathogenesis of alcohol use disorder (AUD). Toll-like receptors (TLRs) are a group of pattern recognition receptors (PRRs) expressed on both immune cells, including microglia and astrocytes, and non-immune cells in the central nervous system (CNS). Studies have shown that alcohol activates TLR4 signaling, resulting in the induction of pro-inflammatory cytokines and chemokines in the CNS. However, the effect of alcohol on signaling pathways downstream of TLR4, such as MyD88 and TRIF (TICAM) signaling, has not been evaluated extensively. In the current study, we treated male wild-type, TLR4-, MyD88-, and TRIF-deficient mice using a chronic plus binge mouse model of AUD. Evaluation of mRNA expression by qRT-PCR revealed that ethanol increased IL-1β, TNF-α, CCL2, COX2, FosB, and JunB in the cerebellum in wild-type and TRIF-deficient mice, while ethanol generally did not increase the expression of these molecules in TLR4- and MyD88-deficient mice. Furthermore, IRF3, IRF7, and IFN-β1, which are associated with the TRIF-dependent signaling cascade, were largely unaffected by alcohol. Collectively, these results suggest that the TLR4 and downstream MyD88-dependent signaling pathways are essential in ethanol-induced neuroinflammation in this mouse model of AUD.
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Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.3390/cells12162109
- https://www.mdpi.com/2073-4409/12/16/2109/pdf?version=1692590834
- OA Status
- gold
- Cited By
- 22
- References
- 53
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W4386029768
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Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W4386029768Canonical identifier for this work in OpenAlex
- DOI
-
https://doi.org/10.3390/cells12162109Digital Object Identifier
- Title
-
Ethanol Induces Neuroinflammation in a Chronic Plus Binge Mouse Model of Alcohol Use Disorder via TLR4 and MyD88-Dependent SignalingWork title
- Type
-
articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2023Year of publication
- Publication date
-
2023-08-21Full publication date if available
- Authors
-
Kalee N. Holloway, James C. Douglas, Tonya Rafferty, Cynthia J.M. Kane, Paul D. DrewList of authors in order
- Landing page
-
https://doi.org/10.3390/cells12162109Publisher landing page
- PDF URL
-
https://www.mdpi.com/2073-4409/12/16/2109/pdf?version=1692590834Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
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https://www.mdpi.com/2073-4409/12/16/2109/pdf?version=1692590834Direct OA link when available
- Concepts
-
TRIF, Neuroinflammation, TLR4, Microglia, Signal transduction, HMGB1, Chemokine, Receptor, Alcohol use disorder, Immunology, Cell biology, Toll-like receptor, Biology, Innate immune system, Immune system, Chemistry, Inflammation, Medicine, Internal medicine, Biochemistry, AlcoholTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
22Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 14, 2024: 8Per-year citation counts (last 5 years)
- References (count)
-
53Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| abstract_inverted_index.treated | 93 |
| abstract_inverted_index.However, | 65 |
| abstract_inverted_index.IFN-β1, | 155 |
| abstract_inverted_index.alcohol. | 168 |
| abstract_inverted_index.believed | 5 |
| abstract_inverted_index.cascade, | 163 |
| abstract_inverted_index.disorder | 14 |
| abstract_inverted_index.increase | 140 |
| abstract_inverted_index.pathways | 72, 180 |
| abstract_inverted_index.revealed | 116 |
| abstract_inverted_index.Toll-like | 16 |
| abstract_inverted_index.activates | 50 |
| abstract_inverted_index.cytokines | 59 |
| abstract_inverted_index.essential | 182 |
| abstract_inverted_index.evaluated | 86 |
| abstract_inverted_index.expressed | 27 |
| abstract_inverted_index.generally | 137 |
| abstract_inverted_index.including | 32 |
| abstract_inverted_index.increased | 119 |
| abstract_inverted_index.induction | 56 |
| abstract_inverted_index.microglia | 33 |
| abstract_inverted_index.molecules | 145 |
| abstract_inverted_index.receptors | 17, 25 |
| abstract_inverted_index.resulting | 53 |
| abstract_inverted_index.signaling | 71, 162, 179 |
| abstract_inverted_index.wild-type | 131 |
| abstract_inverted_index.Evaluation | 110 |
| abstract_inverted_index.associated | 158 |
| abstract_inverted_index.cerebellum | 129 |
| abstract_inverted_index.chemokines | 61 |
| abstract_inverted_index.contribute | 7 |
| abstract_inverted_index.downstream | 73, 177 |
| abstract_inverted_index.expression | 113, 142 |
| abstract_inverted_index.non-immune | 37 |
| abstract_inverted_index.signaling, | 52, 82 |
| abstract_inverted_index.unaffected | 166 |
| abstract_inverted_index.wild-type, | 95 |
| abstract_inverted_index.astrocytes, | 35 |
| abstract_inverted_index.recognition | 24 |
| abstract_inverted_index.Furthermore, | 151 |
| abstract_inverted_index.extensively. | 87 |
| abstract_inverted_index.pathogenesis | 10 |
| abstract_inverted_index.Collectively, | 169 |
| abstract_inverted_index.TRIF-deficient | 99, 133 |
| abstract_inverted_index.TRIF-dependent | 161 |
| abstract_inverted_index.MyD88-deficient | 149 |
| abstract_inverted_index.MyD88-dependent | 178 |
| abstract_inverted_index.ethanol-induced | 184 |
| abstract_inverted_index.pro-inflammatory | 58 |
| abstract_inverted_index.neuroinflammation | 185 |
| abstract_inverted_index.neuroinflammation, | 2 |
| cited_by_percentile_year.max | 100 |
| cited_by_percentile_year.min | 99 |
| corresponding_author_ids | https://openalex.org/A5055938141 |
| countries_distinct_count | 1 |
| institutions_distinct_count | 5 |
| corresponding_institution_ids | https://openalex.org/I79620101 |
| sustainable_development_goals[0].id | https://metadata.un.org/sdg/3 |
| sustainable_development_goals[0].score | 0.7099999785423279 |
| sustainable_development_goals[0].display_name | Good health and well-being |
| citation_normalized_percentile.value | 0.92973578 |
| citation_normalized_percentile.is_in_top_1_percent | False |
| citation_normalized_percentile.is_in_top_10_percent | True |