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.

A Cross-Sectional Study Evaluating the Effects of Resistance Exercise on Inflammation and Neurotrophic Factors in Elderly Women with Obesity

“…The results of this study showed that NF-κB levels were significantly decreased after resistance exercise in the EG, and this group showed significantly lower IFN-γ levels than the CG. These results are congruent with the results of previous studies that reported a significant decrease in NF-κB and IFN-γ levels after exercise training in humans with metabolic syndrome [35][36][37] and those of studies showing that resistance exercise can alleviate neuroinflammation in rodent models [38]. Balducci et al reported that anti-inflammatory effects of exercise training depended on exercise modalities, regardless of weight loss because serum IFN-γ levels of subjects with metabolic syndrome were significantly decreased when aerobic exercises were combined with anaerobic exercises rather than when only aerobic exercises were performed by patients with metabolic syndrome [36].…”

Neuroprotective Effects of Chronic Resveratrol Treatment and Exercise Training in the 3xTg-AD Mouse Model of Alzheimer’s Disease

“…Recent studies have also supported these beneficial effects of treadmill or wheel running initiated in young mice on AD-related pathology, including decreases in Aβ 1–40 and 1–42 in the hippocampus and cerebral cortex after 20 weeks of treadmill running initiated in 4-month-old 3xTg-AD mice fed a high-fat diet [ 23 ] and after 12 weeks of treadmill running in 3 month-old 3xTg-AD mice [ 21 ]. In addition to the benefits afforded by aerobic exercise training, resistance training attenuates the amyloid burden in the 3xTg-AD mouse regardless of the age of mice at the onset of exercise [ 19 , 20 ]. It is evident from these studies that exercise, regardless of the form, slows the accumulation of Aβ species.…”

“…Exercise training (ET) performed on a regular basis improves the quality of life and reduces the incidence of cognitive defects and the progression of AD [ 15 , 16 , 17 ]. In the 3xTg mouse model of AD, ET affords neuroprotection by reducing Aβ content [ 18 , 19 ], inflammation and apoptosis in the hippocampus [ 20 , 21 , 22 , 23 ] and by improving mitochondrial function and neurogenesis [ 21 ]. Similarly, the consumption of natural products containing polyphenols has gained interest as a non-pharmacological approach for the treatment and prevention of AD.…”

“…Therefore, considering the benefits of both ET and the consumption of Resv in the prevention of neurodegenerative diseases, the purpose of this study was to examine the role of ET and dietary supplementation with Resv on different conformational toxic species of Aβ, Aβ-induced apoptosis, inflammation, neuroprotection, and regulation of the endolysosomal pathway in the 3xTg mouse. Since previous studies have indicated that ET alone is protective against neurodegeneration [ 18 , 19 , 20 , 21 , 22 , 23 ], we aimed to determine whether the combined treatment of ET with Resv supplementation would provide added protection against the development of AD-induced pathology.…”

Modulation of MicroRNAs as a Potential Molecular Mechanism Involved in the Beneficial Actions of Physical Exercise in Alzheimer Disease

“…Resistance training in 3xTg-AD mice also reduced the accumulation of Aβ and Tau protein, reduced expression of TNF-α and IL-1β, increased expression of IL-6, IL-10, Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and fibroblast growth factor 21 (FGF-21), increased the expression of structural synaptic proteins, and improved cognitive function. These benefits may also be associated with AKT, GSK-3β, and JNK signaling pathways that were modulated by PE [ 214 ].…”