Effects of an Exercise Program Combining Aerobic and Resistance Training on Protein Expressions of Neurotrophic Factors in Obese Rats Injected with Beta-Amyloid

Abstract

In this study, the effects of a 12-week exercise program combining aerobic and resistance training on high-fat diet-induced obese Sprague Dawley (SD) rats after the injection of beta-amyloid into the cerebral ventricle were investigated. Changes in physical fitness, cognitive function, blood levels of beta-amyloid and metabolic factors, and protein expressions of neurotrophic factors related to brain function such as BDNF (brain-derived neurotrophic factor) in the quadriceps femoris, hippocampus, and cerebral cortex were analyzed. The subjects were thirty-two 10-week-old SD rats (DBL Co., Ltd., Seoul, Korea). The rats were randomized into four groups: β-Non-Ex group (n = 8) with induced obesity and βA25-35 injection into the cerebral ventricle through stereotactic biopsy; β-Ex group (n = 8) with induced obesity, βA25-35 injection, and exercise; S-Non-Ex group (n = 8) with an injection of saline in lieu of βA25-35 as the control; and S-Ex group (n = 8) with saline injection and exercise. The 12-week exercise program combined aerobic training and resistance training. As for protein expressions of the factors related to brain function, the combined exercise program was shown to have a clear effect on activating the following factors: PGC-1α (peroxisome proliferator-activated receptor gamma coactivator 1-alpha), FNDC5 (fibronectin type III domain-containing protein 5), and BDNF in the quadriceps femoris; TrkB (Tropomyosin receptor kinase B), FNDC5, and BDNF in the hippocampus; PGC-1α, FNDC5, and BDNF in the cerebral cortex. The protein expression of β-amyloid in the cerebral cortex was significantly lower in the β-Ex group than in the β-Non-Ex group (p < 0.05). The 12-week intervention with the combined exercise program of aerobic and resistance training was shown to improve cardiopulmonary function, muscular endurance, and short-term memory. The results demonstrate a set of positive effects of the combined exercise program, which were presumed to have arisen mainly due to its alleviating effect on β-amyloid plaques, the main cause of reduced brain function, as well as the promotion of protein expressions of PGC-1α, FNDC5, and BDNF in the quadriceps femoris, hippocampus, and cerebral cortex.

Exercise Regulates Myokines in Aging-Related Diseases through Muscle-Brain Crosstalk

“…Moreover, the application of such exercise was mostly seen in related studies on BDNF expression. One study [75] found that after 12 weeks of daily moderate-intensity combined AE and RE training for obese SD rats injected with Aβ protein, the expression of peroxisome proliferator-activated receptor gamma coactivator-1α, FNDC5, and BDNF protein in the rats was activated, and the level of BDNF increased. Short-term memory and spatial perception abilities were improved in the passive avoidance test and Morris water maze test.…”

“…These myokines may play a neuroprotective, antiinflammatory role in preventing the progression of AD before it is developed and may also slow the progression of the disease after it is developed and prevent it from worsening. Studies on AE intervention after cognitive decline also found that cognitive function tests such as the Exercise Regulates Myokines through Muscle-Brain Crosstalk Morris water maze test and Stroop interference test showed better results than before [44,75]. Current studies on exercise-regulating myokines mostly use exercise with a frequency of 3 times a week.…”

The effects of resistance exercise on cognitive function, amyloidogenesis, and neuroinflammation in Alzheimer’s disease

“…RE applied in old animals or animal models of AD, using exercise programs lasting between 4 and 12 weeks, increased BDNF levels in the hippocampus (Özbeyli et al, 2017;Vilela et al, 2017;Jafarzadeh et al, 2021;Kim et al, 2021;Lee et al, 2022;Rahmati et al, 2022). Two of these studies also showed increased levels of exercise-induced NGF (Jafarzadeh et al, 2021;Rahmati et al, 2022) Frontiers in Neuroscience 04 frontiersin.org the brain of resistance-trained animals (Pena et al, 2020).…”

The Related Metabolic Diseases and Treatments of Obesity

“…A meta-analysis study shows that exercise, especially aerobic exercise, significantly decreases the N-terminal-pro hormone B-type natriuretic peptide (BNP) in patients with heart failure, regardless of obesity status [ 89 ]. A 12 week exercise program combining aerobic and resistance training on obese β-amyloid-treated rats significantly alleviated the side effects of β-amyloid plaque on brain function, and improved cardiopulmonary function, muscular endurance, and short-term memory ability [ 90 ]. This exercise training also activated the expression of many proteins that are associated with brain function in the hippocampus and cerebral cortex, including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), fibronectin type III domain-containing protein 5 (FNDC5), and brain-derived neurotrophic factor (BDNF).…”