ArticleNeuropharmacology2017
Phosphodiesterase 4b expression plays a major role in alcohol-induced neuro-inflammation.
Article in Neuropharmacology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 49 citations in OpenAlex.
- Baseline C-reactive protein levels are predictive of treatment response to a neuroimmune modulator in individuals with an alcohol use disorder: a preliminary study.The American journal of drug and alcohol abuse · 2023Trial
- The effect of neuroimmune modulation on subjective response to alcohol in the natural environment.Alcoholism, clinical and experimental research · 2022Trial
- Context-dependent effects of microglial MyD88 removal on voluntary ethanol consumption in mice.Neuropharmacology · 2026Article
- Global deletion ofbioRxiv : the preprint server for biology · 2026Article
- Identification of novel reproducible combinatorial genetic risk factors for myalgic encephalomyelitis in the DecodeME patient cohort and commonalities with long COVID.Journal of translational medicine · 2026Article
- Alcohol addiction and Alzheimer's disease: a molecular collision course.Translational psychiatry · 2025Review
- Inhibition of PDE4B ameliorates cognitive defects in the model of alcoholic dementia in 3xTg-AD mice via PDE4B/cAMP/PKA signaling.The international journal of neuropsychopharmacology · 2025Article
- In the Brain of Phosphodiesterases: Potential Therapeutic Targets for Schizophrenia.Clinical psychopharmacology and neuroscience : the official scientific journal of the Korean College of Neuropsychopharmacology · 2025Review
- Alcohol drinking is attenuated by PDE4 inhibition but partial microglia depletion is not sufficient to block stress-induced escalation of alcohol intake in female mice.Alcohol (Fayetteville, N.Y.) · 2025Article
- Microglial circDlg1 modulates neuroinflammation by blocking PDE4B ubiquitination-dependent degradation associated with Alzheimer's disease.Theranostics · 2025Article
- PET imaging in rat brain shows opposite effects of acute and chronic alcohol exposure on phosphodiesterase-4B, an indirect biomarker of cAMP activity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- Zoledronic Acid Accelerates ER Stress-Mediated Inflammation by Increasing PDE4B Expression in Bisphosphonate-Related Osteonecrosis of the Jaw.Applied biochemistry and biotechnology · 2024Article
- Neuroimmune Activation and Microglia Reactivity in Female Rats Following Alcohol Dependence.International journal of molecular sciences · 2024Article
- Cell-type brain-region specific changes in prefrontal cortex of a mouse model of alcohol dependence.Neurobiology of disease · 2024Article
- Increased expression of phosphodiesterase 4 in activated hepatic stellate cells promotes cytoskeleton remodeling and cell migration.The Journal of pathology · 2023Article
- Exacerbating effects of single-dose acute ethanol exposure on neuroinflammation and amelioration by GPR110 (ADGRF1) activation.Journal of neuroinflammation · 2023Article
- Review
- Targeting Persistent Changes in Neuroimmune and Epigenetic Signaling in Adolescent Drinking to Treat Alcohol Use Disorder in Adulthood.Pharmacological reviews · 2023Review
- The protective effect of Palmatine on depressive like behavior by modulating microglia polarization in LPS-induced mice.Neurochemical research · 2022Article
- Sex differences in stress-induced alcohol intake: a review of preclinical studies focused on amygdala and inflammatory pathways.Psychopharmacology · 2022Review
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
It is increasingly evident that alcohol-induced, gut-mediated peripheral endotoxemia plays a significant role in glial cell activation and neuro-inflammation. Using a mouse model of chronic alcohol feeding, we examined the causal role of endotoxin- and cytokine-responsive Pde4 subfamily b (Pde4b) expression in alcohol-induced neuro-inflammation. Both pharmacologic and genetic approaches were used to determine the regulatory role of Pde4b. In C57Bl/6 wild type (WT) alcohol fed (WT-AF) animals, alcohol significantly induced peripheral endotoxemia and Pde4b expression in brain tissue, accompanied by a decrease in cAMP levels. Further, along with Pde4b, there was a robust activation of astrocytes and microglia accompanied by significant increases in the inflammatory cytokines (Tnfα, Il-1β, Mcp-1 and Il-17) and the generalized inflammatory marker Cox-2. At the cellular level, alcohol and inflammatory mediators, particularly LPS, Tnfα and Hmgb1 significantly activated microglial cells (Iba-1 expression) and selectively induced Pde4b expression with a minimal to no change in Pde4a and d isoforms. In comparison, the alcohol-induced decrease in brain cAMP levels was completely inhibited in WT mice treated with the Pde4 specific pharmacologic inhibitor rolipram and in Pde4b-/- mice. Moreover, all the observed markers of alcohol-induced brain inflammation were markedly attenuated. Importantly, glial cell activation induced by systemic endotoxemia (LPS administration) was also markedly decreased in Pde4b-/- mice. Taken together, these findings strongly support the notion that Pde4b plays a critical role in coordinating alcohol-induced, peripheral endotoxemia mediated neuro-inflammation and could serve as a significant therapeutic target.
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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.