How chronic stress and the protein REDD1 in the frontal brain can make it harder to adapt
Chronic stress-induced REDD1 expression in prefrontal cortex and cognitive inflexibility
This work looks at whether long-term stress raises a brain protein called REDD1 in the frontal cortex and helps explain why people with stress-related depression often have trouble adapting their thinking.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | Medical College of Wisconsin NIH-funded |
| Lab location | 1 site (Milwaukee, United States) |
| Project ID | NIH-11232332 on NIH RePORTER |
What this research studies
The team uses a mouse model that mimics long-term unpredictable stress to reproduce thinking problems seen in people with depression. They focus on a specific group of frontal cortex nerve cells that carry D2 dopamine receptors and measure tiny connections called dendritic spines. Researchers will compare males and females because early results suggest the effect differs by sex, and they will link changes in the protein REDD1 to both brain-cell structure and behavior on strategy-switching tasks. Together the experiments aim to map a chain from stress to molecular change to altered brain wiring and inflexible thinking.
Who could benefit from this research
Good fit: The project is most relevant to adults with stress-related major depressive disorder who experience cognitive inflexibility, though the experiments are currently performed in animals rather than enrolling patients.
Not a fit: People without stress-linked depression or whose thinking problems come from other medical causes are less likely to benefit directly from this specific line of work.
Why it matters
Potential benefit: If successful, this work could point to new molecular targets for treatments that improve mental flexibility in stress-related depression.
How similar studies have performed: Prior animal studies have linked REDD1 and chronic stress to mood and brain changes, but targeting REDD1 in specific frontal neuron subtypes and translating that to human treatments remains relatively novel.
Where this research is happening
Milwaukee, United States
- Medical College of Wisconsin — Milwaukee, United States (Active)
Researchers
- Principal investigator: Mantsch, John R — Medical College of Wisconsin
- Study coordinator: Mantsch, John R
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.