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Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer's disease mice.

ABSTRACT: BACKGROUND:Both human and animal studies have shown beneficial effects of physical exercise on brain health but most tend to be based on aerobic rather than resistance type regimes. Resistance exercise has the advantage of improving both muscular and cardiovascular function, both of which can benefit the frail and the elderly. However, the neuroprotective effects of resistance training in cognitive impairment are not well characterized. METHODS:We evaluated whether short-term resistant training could improve cognitive function and pathological changes in mice with pre-existing cognitive impairment. Nine-month-old 3xTg mouse underwent a resistance training protocol of climbing up a 1-m ladder with a progressively heavier weight loading. RESULTS:Compared with sedentary counterparts, resistance training improved cognitive performance and reduced neuropathological and neuroinflammatory changes in the frontal cortex and hippocampus of mice. In line with these results, inhibition of pro-inflammatory intracellular pathways was also demonstrated. CONCLUSIONS:Short-term resistance training improved cognitive function in 3xTg mice, and conferred beneficial effects on neuroinflammation, amyloid and tau pathology, as well as synaptic plasticity. Resistance training may represent an alternative exercise strategy for delaying disease progression in Alzheimer's disease.

SUBMITTER: Liu Y

PROVIDER: S-EPMC6942350 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer's disease mice.

Liu Yan Y Chu John Man Tak JMT Yan Tim T Zhang Yan Y Chen Ying Y Chang Raymond Chuen Chung RCC Wong Gordon Tin Chun GTC

Journal of neuroinflammation 20200103 1

<h4>Background</h4>Both human and animal studies have shown beneficial effects of physical exercise on brain health but most tend to be based on aerobic rather than resistance type regimes. Resistance exercise has the advantage of improving both muscular and cardiovascular function, both of which can benefit the frail and the elderly. However, the neuroprotective effects of resistance training in cognitive impairment are not well characterized.<h4>Methods</h4>We evaluated whether short-term resi ...[more]

PMID: 31900170

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Project description:BackgroundMechanical ventilation is strongly associated with cognitive decline after critical illness. This finding is particularly evident among older individuals who have pre-existing cognitive impairment, most commonly characterized by varying degrees of cerebral amyloid-? accumulation, neuroinflammation, and blood-brain barrier dysfunction. We sought to test the hypothesis that short-term mechanical ventilation contributes to the neuropathology of cognitive impairment by (i) increasing cerebral amyloid-? accumulation in mice with pre-existing Alzheimer's disease pathology, (ii) increasing neurologic and systemic inflammation in wild-type mice and mice with pre-existing Alzheimer's disease pathology, and (iii) increasing hippocampal blood-brain barrier permeability in wild-type mice and mice with pre-existing Alzheimer's disease pathology.MethodsWe subjected double transgenic Alzheimer's disease (APP/PSEN1) and wild-type mice to mechanical ventilation for 4?h and compared to non-mechanically ventilated Alzheimer's disease model and wild-type mice. Cerebral soluble/insoluble amyloid-?1-40/amyloid-?1-42 and neurological and systemic markers of inflammation were quantified. Hippocampal blood-brain barrier permeability was quantified using a novel methodology that enabled assessment of small and large molecule permeability across the blood-brain barrier.ResultsMechanical ventilation resulted in (i) a significant increase in cerebral soluble amyloid-?1-40 (p?=?0.007) and (ii) significant increases in neuroinflammatory cytokines in both wild-type and Alzheimer's disease mice which, in most cases, were not reflected in the plasma. There were (i) direct correlations between polymorphonuclear cells in the bronchoalveolar fluid and cerebral soluble amyloid-?1-40 (p?=?0.0033), and several Alzheimer's disease-relevant neuroinflammatory biomarkers including cerebral TNF-? and IL-6; (iii) significant decreases in blood-brain barrier permeability in mechanically ventilated Alzheimer's disease mice and a trend towards increased blood-brain barrier permeability in mechanically ventilated wild-type mice.ConclusionsThese results provide the first evidence that short-term mechanical ventilation independently promotes the neuropathology of Alzheimer's disease in subjects with and without pre-existing cerebral Alzheimer's disease pathology. Future studies are needed to further clarify the specific mechanisms by which this occurs and to develop neuroprotective mechanical ventilation strategies that mitigate the risk of cognitive decline after critical illness.

Project description:Older adults have reduced fluid intake and impaired body fluid and electrolyte regulation. Older female adults exhibit exaggerated exercise blood pressure (BP) responses, which is associated with an increased risk of adverse cardiovascular events. However, it is unclear if dysregulated body fluid homeostasis contributes to altered exercise BP responses in older female adults. We tested the hypothesis that short-term water deprivation (WD) increases exercise BP responses in older female adults. Fifteen female adults (eight young [25 ± 6 years] and seven older [65 ± 6 years]) completed two experimental conditions in random crossover fashion; a euhydration control condition and a stepwise reduction in water intake over three days concluding with a 16-hr WD period. During both trials, beat-to-beat BP (photoplethysmography) and heart rate (electrocardiogram) were continuously assessed during rest, handgrip exercise (30% MVC), and post-exercise ischemia (metaboreflex isolation). At screening, older compared to young female adults had greater systolic and diastolic BP (p ≤ .02). Accelerometer-assessed habitual physical activity was not different between groups (p = .65). Following WD, 24-hr urine flow rate decreased, whereas thirst, urine specific gravity, and plasma osmolality increased (condition: p < .05 for all), but these WD-induced changes were not different between age groups (interaction: p ≥ .31 for all). Resting systolic and diastolic BP values were higher in older compared to young adults (p < .01 for both), but were not different between experimental conditions (p ≥ .20). In contrast to our hypothesis, WD was associated with attenuated systolic BP responses during handgrip exercise (post hoc: p < .01) and post-exercise ischemia (post hoc: p = .03) in older, but not young, female adults. These data suggest that reduced water intake-induced challenges to body fluid homeostasis do not contribute to exaggerated exercise BP responses in post-menopausal female adults.

Dataset Information

Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer's disease mice.

Publications

Short-term resistance exercise inhibits neuroinflammation and attenuates neuropathological changes in 3xTg Alzheimer's disease mice.

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