Acute Exercise and Brain BACE1 Protein Content: a Time Course Study
Bibliographic record
Abstract
Obesity and type 2 diabetes are significant risk factors in the development of neurodegenerative disorders, such as Alzheimer's disease (AD). A variety of cellular mechanisms, such as altered insulin and stress‐signaling contribute to neurodegeneration, and have been linked to increases in beta‐site amyloid precursor protein cleaving enzyme 1 (BACE1). BACE1 is the rate limiting enzyme in the production of amyloid‐beta peptides which are implicated in the pathology of AD. Previous work suggests that a single, acute bout of exercise may have beneficial neuro‐protective effects in the prefrontal cortex of obese mice, independent of weight loss. The purpose of this study was to examine‐ how long the exercise induced alterations in the prefrontal cortex persist following a single exercise bout. Male C57BL/6 mice were fed either a low (LFD, 10% kcals from lard) or a high fat diet (HFD, 60% kcals from lard) for 7 weeks. HFD mice then underwent an acute bout of exercise (treadmill running: 15 m/min, 5% incline, 120 min) followed by a recovery period of 2, 8, or 24 hours. The HFD resulted in increased body mass (LFD 27.8±1.05 vs HFD 41.7±0.60 g; p<0.05) and glucose intolerance (AUC LFD 63.27±4.5 vs HFD 128.9±4.6; p<0.05). In the prefrontal cortex, BACE1 protein content was reduced 2‐ and 8‐hours post‐exercise compared to the sedentary HFD group, however BACE1 protein content 24‐hours post‐exercise was not different (p<0.05). Compared to the LFD, the HFD had higher prefrontal cortex phosphorylation of p38, JNK, and Akt (Ser473), with no changes in ERK phosphorylation, indicative of increased neuronal stress and aberrant insulin signaling. Post‐exercise p38 and JNK phosphorylation were no different from either the HFD or LFD groups, while ERK phosphorylation was significantly reduced by 24‐hours of recovery. These changes were accompanied by an increase in circulating BDNF (pg/ml) at 24‐hour recovery (p<0.01). Our results suggest that a single, acute bout of exercise may have beneficial neuro‐protective effects in obesity. We provide evidence that an acute bout of exercise can reduce markers of stress‐signaling pathways as well as BACE1 protein content in the prefrontal cortex. However, the reduction in BACE1 content is short lived and highlights the importance of daily exercise interventions for long‐term improvements in early AD‐associated pathology. Support or Funding Information Supported by Alzheimer Society of Brant, Haldimand, Norfolk, Hamilton, and Halton PI:REKM This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| 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) | 0.001 | 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 source (direct Gemma or distilled Codex), 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".