Related Experiment Video
Updated: May 12, 2026
Isolation, Proliferation and Differentiation of Rhesus Macaque Adipose-Derived Stem Cells
Published on: May 26, 2021
Chronic alcohol consumption induces phenotypic and functional alterations consistent with a hyper-inflammatory state
Hami Hemati1, Madison B Blanton2, Heather E True2
1Microbiology, Immunology and Molecular Genetics, College of Medicine, University of Kentucky, Lexington, KY, United States.
Abstract:
Alcohol-induced dysregulation of microglial activity is associated with neuroinflammation, cognitive decline, heightened risk for neurodegenerative diseases, alcohol dependence, and escalation of alcohol drinking. Given the challenge of longitudinally sampling primary microglia, we optimized an in vitro method to differentiate peripheral blood mononuclear cells (PBMC) from rhesus macaque (RM) into induced microglia-like cells (RM-iMGLs). The RM-iMGLs displayed transcriptional profiles distinct from monocyte progenitors and closely resembling primary microglia. Notably, morphological features showed that differentiated RM-iMGLs derived from subjects with chronic alcohol consumption (CAC), while bigger, exhibited a bipolar-like morphology. Additionally, dysregulation in key inflammatory and regulatory markers, along with increased baseline phagocytic activity, was observed in CAC-derived RM-iMGLs. Phenotypic and functional assessments following LPS stimulation indicated the enrichment of a CD86+ hyper-inflammatory subpopulation in RM-iMGLs derived from ethanol-consuming animals, accompanied by an overall increase in immune reactivity, indicative of a heightened inflammatory state. Collectively, these findings demonstrate that in vitro differentiation of PBMCs offers a minimally invasive yet highly translational approach to studying the impact of CAC on microglial function and that CAC reshapes both functional and transcriptional profiles of RM-iMGLs, which require further investigation at the single-cell level.
Insights
Chronic alcohol consumption alters immune cells, creating microglia-like cells with heightened inflammation. This study optimized a method to study alcohol
Area of Science:
- Neuroscience
- Immunology
- Toxicology
Background:
- Alcohol-induced microglial dysregulation contributes to neuroinflammation and cognitive decline.
- Studying microglia longitudinally is challenging due to difficulties in direct sampling.
- Chronic alcohol consumption (CAC) impacts brain health through neuroinflammatory pathways.
Purpose of the Study:
- To optimize an in vitro method for differentiating rhesus macaque (RM) peripheral blood mononuclear cells (PBMCs) into induced microglia-like cells (RM-iMGLs).
- To investigate the impact of CAC on the function and characteristics of RM-iMGLs.
- To establish a translational model for studying alcohol's effects on microglial activity.
Main Methods:
- Differentiation of RM PBMCs into RM-iMGLs.
- Transcriptional profiling to compare RM-iMGLs with monocyte progenitors and primary microglia.
- Morphological, phenotypic, and functional assessments of RM-iMGLs from control and CAC subjects.
- Lipopolysaccharide (LPS) stimulation to evaluate immune reactivity.
Main Results:
- RM-iMGLs exhibited transcriptional profiles similar to primary microglia, distinct from progenitors.
- CAC-derived RM-iMGLs were larger, showed bipolar-like morphology, and had increased baseline phagocytic activity.
- LPS stimulation revealed a hyper-inflammatory CD86+ subpopulation and heightened immune reactivity in CAC-derived RM-iMGLs.
- CAC reshaped both functional and transcriptional profiles of RM-iMGLs.
Conclusions:
- In vitro differentiation of PBMCs provides a minimally invasive model to study CAC's effects on microglia.
- CAC significantly alters microglial function and inflammatory profiles, suggesting a role in alcohol-related neuroinflammation.
- Further single-cell level investigations are warranted to fully elucidate CAC-induced microglial changes.
More Related Videos
05:12Chronic Intermittent Ethanol Vapor Exposure Paired with Two-Bottle Choice to Model Alcohol Use Disorder
Published on: June 23, 2023
08:37Assessment of Glutamine as a Fuel Source for Alveolar Macrophages Exposed to Chronic Ethanol Using an Extracellular Flux Bioanalyzer
Published on: November 15, 2024
Related Concept Videos
01:23Cirrhosis I: Introduction
01:24Cirrhosis II: Pathophysiology