How alcohol changes a brain receptor that controls a calming neurosteroid
Alcohol-induced epigenetic reprogramming of PPAR-α affects allopregnanolone biosynthesis
The team wants to learn if long-term alcohol use changes the brain receptor PPAR-α and lowers the calming neurosteroid allopregnanolone in people with alcohol problems.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Illinois at Chicago NIH-funded |
| Lab location | 1 site (Chicago, UNITED STATES) |
| Project ID | NIH-11125908 on NIH RePORTER |
What this research studies
From the patient perspective, researchers combine animal models and human brain tissue to track how chronic alcohol exposure alters genes and epigenetic marks that control production of the calming neurosteroid allopregnanolone. They measure key enzymes (like 5α-reductase and 3α-HSD) and DNA methylation patterns in corticolimbic brain regions affected by alcohol. The team will test whether activating the nuclear receptor PPAR-α with the natural compound palmitoylethanolamide (PEA) can restore neurosteroid levels and reduce anxiety and alcohol seeking in models. Findings from postmortem human brain samples will be compared to the animal results to strengthen relevance to people with alcohol use disorder.
Who could benefit from this research
Good fit: Adults with alcohol use disorder or a history of heavy drinking who experience withdrawal-related anxiety would be the most directly relevant group.
Not a fit: People without alcohol problems or whose symptoms stem from unrelated medical or psychiatric causes may not benefit from these findings.
Why it matters
Potential benefit: If successful, this work could point to new ways to boost calming neurosteroids or target PPAR-α to ease withdrawal-related anxiety and reduce drinking.
How similar studies have performed: Preclinical studies have shown PPAR-α activation and neurosteroid manipulation can reduce anxiety and alcohol intake in animals, but translating this into proven human treatments is still early.
Where this research is happening
Chicago, UNITED STATES
- University of Illinois at Chicago — Chicago, United States (Active)
Researchers
- Principal investigator: Pinna, Graziano — University of Illinois at Chicago
- Study coordinator: Pinna, Graziano
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.