Impact of Physical Exercise on the Hippocampal Pathology and Cognition in a Mouse Model of Alzheimer's Disease
Bibliographic record
Abstract
It is recognized that neuronal and vascular functions are affected during the progression of Alzheimer’s disease (AD). The accumulation of amyloid-beta peptides (Aβ) in the parenchyma and around blood vessels can contribute to neuronal and vascular compromise, and exacerbate cognitive impairment. Exercise has been described as one of the most influential modulators at preventing cognitive deficits observed in AD. The present work examined the extent to which physical activity is capable of reducing Aβ-related pathologies. I hypothesized that physical exercise stimulates memory and neurogenesis, remodels vasculature and lessens Aβ burden in the hippocampus of TgCRND8 mouse model of amyloidosis. All animals entered the study at 3 months of age and separate cohorts ran for 1, 2, or 3 months. My results indicate that voluntary running promotes spatial memory, neurogenesis, and cerebrovascular morphology in TgCRND8 mice. Specifically, the number of proliferating cells was significantly greater in running compared to non-running (sedentary) TgCRND8 mice as disease progressed. The number of doublecortin-positive new immature neurons was higher in TgCRND8 mice running for 1 month, compared to sedentary transgenics. Neuronal maturation was increased after 2 months (and not 1 month) of running in TgCRND8 mice. Running reduced plaque load in the dentate gyrus and Cornu Ammonis subregions of the hippocampus only after 2 months (5 month-old mice), and not after 1 month (4 month-old mice) or 3 months (6 month-old mice) of exercise. In 6 month-old mice, cerebral amyloid angiopathy levels were significantly reduced in running compared to sedentary mice. At 6 months of age, sedentary TgCRND8 mice had higher capillary density, capillary length, branch density, and non-capillary tortuosity compared to age-matched non-transgenics. These changes in vascular morphology suggest an adaptative response to Aβ pathology. In contrast, the vascular parameters of TgCRND8 mice running for 3 months were indistinguishable from non-transgenics animals. Memory improvements were observed at 4, 5 and 6 months of age in TgCRND8 mice running for 1, 2, and 3 months, respectively. Running TgCRND8 mice spent more time in the novel arm of the Y-maze compared to the familiar arms. Overall, these data indicate that as amyloidosis progresses in the hippocampus of TgCRND8 mice, physical exercise has a pronounced impact on cognition, with spatial memory rescued even when the number of new mature neurons (at 4 months) and plaque burden (at 4 and 6 months) are not significantly altered compared to sedentary transgenic animals. These data suggest that increasing neurogenesis and lowering plaque buildup may not be individually necessary to promote cognitive function. In conclusion, this work demonstrates that exercise as a lifestyle modification can improve cognition and reduce the negative impact of AD-related hippocampal pathologies.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| 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".