Can exercise protect against chronic stress induced cerebral microvessel changes in Lean and Obese Zucker rats?
Bibliographic record
Abstract
Background Chronic stress‐induced depression is a major cardiovascular risk factor, and metabolic Syndrome (MetS) is linked with depression. The relationship among chronic stress/depression (UCMS), MetS, CVD, and cerebrovascular dysfunction is poorly understood. We determined how UCMS and Exercise training affected cerebral microvessels density (MVD), and the pro (nitric oxide, VEGF, STAT3) and anti (TSP‐1) angiogenic factors. We hypothesize that UCMS will decrease MVD in Obese Zucker Rats (OZR = MetS), and exercise training will prevent this rarefaction by increasing pro‐angiogenic mediators, while reducing anti‐angiogenic factors including oxidative stress. Methods Nine‐week old lean rats (LZR) and OZR were randomly assigned (n=6/group) to: Control(C), Exercise (EX), subjected daily to an UCMS, and EX+UCMS for 8 weeks. At 17 weeks, brains were removed and snap frozen in Tissue Tek medium. Cortex MVD were measured by fluorescence IHC (rat anti‐CD31 antibody). Oxidative stress was assessed in cerebral tissue by ELISA technique (anti 3‐Nitrotyrosine antibody) and by DHE. Cerebral inflammatory and angiogenic markers for STAT3, VEGF and TSP‐1 were measured by western blot or ELISA. Results MVD was decreased (−31%, p<0.05) in the cortex from OZR‐UCMS vs. OZR control. Exercise training attenuated UCMS induced decreased MVD in OZR by 41%. In contrast, there were no significant differences (8% decrease to 4% increase) in MVD among LZR groups. In both LZR and OZR UCMS increased oxidative stress, and decreased nitric oxide in the cerebral vessels. Although VEGF results were not yet significant, a slight decrease was seen in OZR UCMS that was recovered with exercise training in UCMS. Initial data also suggests that TSP‐1, which is higher in OZR vs. LZR control, is also influenced by UCMS, and Ex. Compared to LZR‐C, LZR‐UCMS had an 74% increase in STAT3. Although both OZR‐C and OZR UCMS exhibited significantly increased STAT3 phosphorylation compared to LZR‐C, there was no difference between OZR‐C and OZR UCMS. Both LZR‐Ex and OZR‐Ex attenuated UCMS induced elevated STAT3 activity. Conclusion Taken together, UCMS drives the development of decreased brain MVD in OZR. Chronic stress and obesity both independently increased STAT3 signaling in the brain, which was then abrogated by exercise in both lean and obese animals. Exercise also prevented the onset of cortical rarefaction seen in OZR‐UCMS. We are further exploring TSP1 and VGEF pathways. Support or Funding Information Acknowledgements: American Physiological Society Short‐Term Experience for Underrepresented Persons Fellowship and the National Institute of Diabetes and Digestive and Kidney Diseases for helping to fund this project. National Institute of Health (5P20GM109098), and National Institute of General Medical Sciences Grant U54 GM‐104942.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".