Hippocampal Growth Factor and Myokine Cathepsin B Expression following Aerobic and Resistance Training in 3xTg-AD Mice

Abstract

Aerobic training (AT) can support brain health in Alzheimer’s disease (AD); however, the role of resistance training (RT) in AD is not well established. Aside from direct effects on the brain, exercise may also regulate brain function through secretion of muscle-derived myokines. Aims. This study examined the effects of AT and RT on hippocampal BDNF and IGF-1 signaling, β-amyloid expression, and myokine cathepsin B in the triple transgenic (3xTg-AD) model of AD. 3xTg-AD mice were assigned to one of the following groups: sedentary (Tg), aerobic trained (Tg+AT, 9 wks treadmill running), or resistance trained (Tg+RT, 9 wks weighted ladder climbing) (n=10/group). Rotarod latency and strength were assessed pre- and posttraining. Hippocampus and skeletal muscle were collected after training and analyzed by high-resolution respirometry, ELISA, and immunoblotting. Tg+RT showed greater grip strength than Tg and Tg+AT at posttraining (p<0.01). Only Tg+AT improved rotarod peak latency (p<0.01). Hippocampal IGF-1 concentration was ~15% greater in Tg+AT and Tg+RT compared to Tg (p<0.05); however, downstream signals of p-IGF-1R, p-Akt, p-MAPK, and p-GSK3β were not altered. Cathepsin B, hippocampal p-CREB and BDNF, and hippocampal mitochondrial respiration were not affected by AT or RT. β-Amyloid was ~30% lower in Tg+RT compared to Tg (p<0.05). This data suggests that regular resistance training reduces β-amyloid in the hippocampus concurrent with increased concentrations of IGF-1. Both types of training offered distinct benefits, either by improving physical function or by modifying signals in the hippocampus. Therefore, inclusion of both training modalities may address central defects, as well as peripheral comorbidities in AD.

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.…”

Effects of Long-Term Endurance Exercise and Lithium Treatment on Neuroprotective Factors in Hippocampus of Obese Rats

“…Most previous studies [56,57] that reported changes in GSK3 β activation by exercise training applied protocols with high exercise intensity or relatively high exercise quantity, and Yang et al [58] reported that GSK3β showed little change at low strength, but it was reported to be significantly changed at medium and high strength. In addition, Pena et al [59] suggested that GSK3β hardly changed even when a relatively large amount of exercise was applied by using a combination of aerobic and resistance exercise. In this study, in order to observe the interaction between exercise and lithium, it was considered that the change in exercise-induced GSK3β was not clearly seen when applied with low intensity from the viewpoint of minimizing exercise stimulation.…”

Modulatory Effect of Myokines on Reactive Oxygen Species in Ischemia/Reperfusion

“…Insulin-like growth factor 1 (IGF-1) is synthesized mainly in the liver and acts as a growth and differentiation factor. IGF-1 is also synthesized by skeletal muscle after physical activity [ 151 , 152 , 153 , 154 ]. Apart from its prominent role in muscle hypertrophy and regeneration, IGF-1 exerts protection against oxidative stress-induced cellular injury.…”