Impact of Physical Exercise on the Hippocampal Pathology and Cognition in a Mouse Model of Alzheimer's Disease
Notice bibliographique
Résumé
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.
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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,001 | 0,000 |
| Méta-épidémiologie (sens large) | 0,001 | 0,001 |
| Bibliométrie | 0,001 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,001 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,001 | 0,000 |
| Intégrité de la recherche | 0,001 | 0,002 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».