Mild Cognitive Impairment in the Presence of Depressive Symptoms Related to Impaired Cerebrovascular Function in the Obese Zucker Rat
Bibliographic record
Abstract
Metabolic syndrome is a highly prevalent constellation of pathologies that frequently combines overweight/obesity, moderate hypertension, atherogenic dyslipidemia, and type II diabetes mellitus, and is accompanied by a systemic vascular pro‐inflammatory, pro‐oxidant condition. The evolution of metabolic syndrome is associated with elevated cerebrovascular disease risk including elevations in both the occurrence and the severity of stroke and transient ischemic attacks within the cerebral circulation. Frequently, these impairments to cerebral vascular function also result in cognitive and behavioral impairments to the afflicted individual even in the absence of an acute pathological event. Given the established elevation in depressive symptoms in OZR that develop in parallel to cerebrovascular dysfunction, we sought to determine the extent to which cognition was impaired. In this study 17–18‐wk‐old male lean and (LZR) obese Zucker rats (OZR) were tested for learning, memory, and behavioral flexibility using an operant conditioning chamber (OCC) and the Morris Water Maze (MWM). Learning was assessed by number of trials to reach 8 correct consecutive responses in OCC or a 6 trial MWM protocol. Performance in a retrieval or probe session 24 h after learning was used to measure memory in OCC and MWM respectively. Behavioral flexibility was measured by analyzing error types in OCC and search strategy in the MWM probe test. Depressive symptoms were measured using coat score, novelty suppressed feeding response, and latency to start grooming and frequency of subsequent grooming after sucrose spray. Ex vivo pressurized middle cerebral arteries (MCA) were used to determine the extent to which metabolic syndrome in OZR alters key indices of vascular reactivity of cerebral resistance vessels and the mechanics of the vascular wall. Endothelium dependent vasodilator reactivity was attenuated in OZR vs LZR in response to acetylcholine. Further impairments were demonstrated in OZR with an increase in depressive symptoms as measured by an increase in coat score and latency to start grooming after sucrose spray as well as mild cognitive impairment measured by increased time to reach the platform in MWM learning trials. In contrast, no signs of cognitive impairment were demonstrated in OCC. These results suggest that the changes in cerebrovascular function in OZR are associated with the development of depressive symptoms and mild cognitive impairment in MWM learning with no changes in learning, memory, or behavior flexibility in OCC at this age. Support or Funding Information CIHR (#130138 and #389769); NSERC (RGPIN‐2018‐05450)
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 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".