Voluntary exercise increases brain tissue oxygenation and spatially homogenizes oxygen delivery in a mouse model of Alzheimer's disease
| Autor: | Samuel Bélanger, Xuecong Lu, Frédéric Lesage, Baoqiang Li, Yuankang Lu, Olivia de Montgolfier, Eric Thorin, Mohammad Moeini |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Aging medicine.medical_specialty Partial Pressure Mice Transgenic Disease Brain tissue 03 medical and health sciences Mice 0302 clinical medicine Oxygen Consumption Alzheimer Disease Internal medicine Physical Conditioning Animal medicine Dementia Animals Amyloid beta-Peptides business.industry General Neuroscience Brain Oxygenation Blood flow Hypoxia (medical) Barrel cortex medicine.disease Oxygen Disease Models Animal 030104 developmental biology Microscopy Fluorescence Multiphoton Turnover Cerebrovascular Circulation Cardiology Neurology (clinical) Geriatrics and Gerontology medicine.symptom business 030217 neurology & neurosurgery Developmental Biology |
| Zdroj: | Neurobiology of aging. 88 |
| ISSN: | 1558-1497 |
| Popis: | Although vascular contributions to dementia and Alzheimer's disease (AD) are increasingly recognized, the potential brain oxygenation disruption associated with AD and whether preventive strategies to maintain tissue oxygenation are beneficial remain largely unknown. This study aimed to examine (1) whether brain oxygenation is compromised by the onset of AD and (2) how voluntary exercise modulates the influence of AD on brain oxygenation. In vivo 2-photon phosphorescence lifetime microscopy was used to investigate local changes of brain tissue oxygenation with the progression of AD and its modulation by exercise in the barrel cortex of awake transgenic AD mice. Our results show that cerebral tissue oxygen partial pressure (PO2) decreased with the onset of AD. Reduced PO2 was associated with the presence of small near-hypoxic areas, an increased oxygen extraction fraction, and reduced blood flow, observations that were all reverted by exercise. AD and age also increased the spatial heterogeneity of brain tissue oxygenation, which was normalized by exercise. Ex vivo staining also showed fewer amyloid-β (Aβ) deposits in the exercise group. Finally, we observed correlations between voluntary running distance and cerebral tissue oxygenation/blood flow, suggesting a dose-response relationship of exercise on the brain. Overall, this study suggests that compromised brain oxygenation is an indicator of the onset of AD, with the emergence of potential deleterious mechanisms associated with hypoxia. Furthermore, voluntary exercise enhanced the neurovascular oxygenation process, potentially offering a means to delay these changes. |
| Databáze: | OpenAIRE |
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