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| Status |
Public on Oct 03, 2024 |
| Title |
Polygenic Risk for Alcohol Use Disorder Affects Cellular Responses to Ethanol Exposure in a Human Microglial Cell Model II |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Polygenic risk scores (PRS) assess genetic susceptibility to Alcohol Use Disorder (AUD), yet their molecular implications remain underexplored. Neuroimmune interactions, particularly in microglia, are recognized as significant contributors to AUD pathophysiology. We investigated the interplay between AUD PRS and ethanol in human microglia derived from iPSCs from individuals with high-or low-PRS (HPRS or LPRS) of AUD. Ethanol exposure induced elevated CD68 expression and morphological changes in microglia, with differential responses between HPRS and LPRS microglial cells. Transcriptomic analysis revealed expression differences in MHCII complex and phagocytosis-related genes following ethanol exposure; HPRS microglial cells displayed enhanced phagocytosis and increased CLEC7Aexpression, unlike LPRS microglial cells. Synapse numbers in co-cultures of induced neurons with microglia after alcohol exposure were lower in HRPS co-cultures, suggesting possible excess synapse pruning. This study provides insights into the intricate relationship between AUD PRS, ethanol, and microglial function, potentially influencing neuronal functions in developing AUD.
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| Overall design |
Cultures were prepared of iPS cells from multiple iPSC lines prepared from subjects with AUD and high polygenic risk (HPRS) and unaffected with low polygenic risk (LPRS). Total cellular RNA was prepared for quality assurance assays.
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| Contributor(s) |
Li X, Liu J, Kreimer A, Hart RP, Pang ZP |
| Citation missing |
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| NIH grant(s) |
| Grant ID |
Grant title |
Affiliation |
Name |
| R01 AA023797 |
Cellular and genomic mechanisms of the impact of ethanol on human neural model |
RUTGERS BIOMEDICAL AND HEALTH SCIENCES |
Zhiping P. Pang |
| U10 AA008401 |
Collaborative Study on the Genetics of Alcoholism (COGA). |
SUNY DOWNSTATE MEDICAL CENTER |
Bernice Porjesz |
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| |
| Submission date |
Jul 05, 2024 |
| Last update date |
Oct 03, 2024 |
| Contact name |
Ronald P. Hart |
| E-mail(s) |
rhart@rutgers.edu
|
| Phone |
848-445-1783
|
| Organization name |
Rutgers University
|
| Department |
Cell Biology & Neuroscience
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| Street address |
604 Allison Rd Rm B430
|
| City |
Piscataway |
| State/province |
NJ |
| ZIP/Postal code |
08854 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA1132252 |
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