Effects of Low-Load, High-Repetition Resistance Training on Maximum Muscle Strength and Muscle Damage in Elite Weightlifters: A Preliminary Study.

This study aimed to assess the impact of different resistance training (RT) loads and repetition on muscle damage, intramuscular anabolic signaling, and maximal muscle strength (MMS) in weightlifters. Eighteen male weightlifters were randomly assigned to 8 weeks of supervised RT regimes: high-load, low-repetition (HL), low-load, high-repetition (LH), and combination of HL and LH (COMBI). All groups exhibited a significant increase in skeletal muscle mass (SMM) and growth hormone levels, which ultimately contributed to improvement in MMS as indicated by 1-repetition maximum in the back squat and back muscle strength. Notably, while there were no significant changes in the mTOR protein, the phosphorylation of phosphorylation of p70 ribosomal protein S6 kinase 1 (p70S6K1), eukaryotic initiation factor 4E-binding protein 1 (4E-BP1), and eukaryotic elongation factor 2 (eEF2), which are involved in muscle cell growth, was significantly affected by the different training regimens. More importantly, LH-RT led to a significant reduction in muscle damage markers, creatine kinase (CK) and lactate dehydrogenase (LDH), suggesting reduced recovery time and fatigue. Our results demonstrated that the LH-RT paradigm could be a viable alternative for weightlifters to enhance MMS and muscle hypertrophy similar to HL-RT, while reducing RT-induced muscle damage, ultimately contributing to the enhancement of exercise performance.

Exercise as an antidepressant: exploring its therapeutic potential.

The COVID-19 pandemic has increased the prevalence of depressive disorders worldwide, requiring alternative treatments beyond medication and psychotherapy. Exercise has positive effects on the brain; therefore, it has emerged as a promising therapeutic option for individuals with depression. Considerable research involving humans and animals offers compelling evidence to support the mental health benefits of physical activity or exercise mediated by the regulation of complex theoretical paradigms. However, challenges such as conducting long-term follow-up assessments and considering individual characteristics remain in human studies despite extensive efforts. While animal studies provide valuable insights into the potential benefits of exercise and its impact on outcomes related to depression and anxiety in rodents exposed to different stress paradigms, translating the findings to humans requires careful evaluation. More research is needed to establish precise exercise prescription guidelines and to better understand the complex relationship between exercise and depressive disorders. Therefore, this concise review explores the evidence supporting exercise intervention as an antidepressant treatment and its underlying mechanisms.

Effect of Home-Based Tele-Pilates Intervention on Pregnant Women: A Pilot Study.

Pilates is effective for training the core muscles and stabilizing the hip joints, which provides relief from pelvic pain and low back pain during pregnancy. However, there are no specific guidelines on appropriate physical exercises for pregnant women due to the current pandemic. We aimed to apply the exercise standard proposed by the American College of Obstetricians and Gynecologists to home-based tele-Pilates exercise (HTPE), to determine its effect on the physical and mental health of pregnant women. We randomly divided the subjects into the following two groups who completed 8 weeks of HTPE (50 min/day, 2 days/week): (a) Pilates exercise (PE, n = 7) and (B) non-Pilates exercise (CON, n = 7). HTPE was performed by adjusting the program every 3 weeks, based on pain and physical fitness levels. We measured body composition, muscles of the hip joint, pelvic tilt, Oswestry Disability Index (ODI), and Pittsburgh Sleep Quality Index (PSQI), before and after HTPE. Following HTPE, while the percentage of body fat and body mass index had significantly decreased, the body fat mass did not change in the PE group (p < 0.05). The PE group showed an increase in strength of the left and right hip flexion and hip abduction, compared to the CON group (p < 0.01). The ODI and PSQI were significantly decreased in the PE group (p < 0.05). Therefore, the 8-week HTPE program is an effective exercise for pregnant woman that reduces body fat metabolism and strengthens muscles of the hip joint, thus alleviating pregnancy-induced low back pain and insomnia.

Exercise Reverses Amyloid ß-Peptide-Mediated Cognitive Deficits in Alzheimer's Disease Mice Expressing Mutant Presenilin-2.

PURPOSE: The molecular mechanisms by which physical exercise produces beneficial effects on pathologic features and behavioral symptoms of Alzheimer's disease (AD) are not well understood. Herein, we examined whether regular moderate exercise could improve cognitive function and produce transcriptomic responses in the brain. METHODS: Four groups of mice were studied: nontransgenic control, mice expressing the human presenilin-2 wild type, mice expressing the human presenilin-2 with the N141I mutation (Tg-PS2m), and Tg-PS2m that were subjected to treadmill exercise (TE) at a speed of 10 m·min-1 for 50 min·d-1, 5 d·wk-1, for 6 wk (Tg-PS2m/Ex). RESULTS: Tg-PS2m/Ex mice exhibited increased preference in exploring a novel object than Tg-PS2m in the novel object recognition test, whereas differences observed in the water maze test and passive avoidance test were not significant. Western blot and histological analyses using amyloid oligomer (A11) and ß-amyloid (6E10) antibody indicated that amyloid oligomer-reactive bands and plaque deposition in the hippocampus were reduced, although not significantly, after TE. Transcriptomic (RNA-sequencing) analysis and subsequent protein analysis revealed that the cell cycle regulatory gene, Cdc28 protein kinase regulatory subunit 2 (Cks2), was decreased, and the cell cycle- and apoptotic cell death-related factors, including cyclin D1, proliferating cell nuclear antigen, and cleaved caspase-3, were increased in the hippocampus of Tg-PS2m, whereas TE reversed their altered expression. CONCLUSIONS: The results support the hypothesis that the pathologic features and behavioral symptoms of AD caused by accumulation of amyloid ß-peptide in hippocampus, causing aberrant cell cycle reentry and apoptosis, can be reversed by regular exercise.

Treadmill Exercise Alleviates Brain Iron Dyshomeostasis Accelerating Neuronal Amyloid-ß Production, Neuronal Cell Death, and Cognitive Impairment in Transgenic Mice Model of Alzheimer's Disease.

Brain iron increases with age and abnormal brain iron metabolism is proving increasingly likely to be involved in the pathology of Alzheimer's disease (AD). The iron-regulatory effect of furin, a ubiquitously expressed proconvertase, might play an important role in AD. Therefore, there is an urgent need to study the effect of furin on iron regulation in AD. For that purpose, we aimed to determine the role of physical exercise in AD associated with brain iron dyshomeostasis. Treadmill exercise attenuated the AD-related abnormal brain iron regulation by furin in vivo, as demonstrated via experiments in aged APP-C105 mice. Next, we examined whether treadmill exercise decreases excessive iron, directly affecting amyloid-ß (Aß) production through the regulation of α-secretase-dependent processing of amyloid protein precursor (APP) involved in the modulation of furin activity. We first observed that cognitive decline and Aß-induced neuronal cell death were induced by disruption of APP processing via excess iron-induced disruption of furin activity in aged APP-C105 mice. The induced cognitive decline and cell death were attenuated by treadmill exercise. This result suggests that treadmill exercise alleviated cognitive decline and Aß-induced neuronal cell death by promoting α-secretase-dependent processing of APP through low iron-induced enhancement of furin activity. This is concomitant with decreasing levels of lipid peroxidation products and promoting antioxidant defense enzyme capacities. Therefore, iron-targeted therapeutic strategies involving treadmill exercise might be useful for patients with AD.

Neuroprotective Benefits of Exercise and MitoQ on Memory Function, Mitochondrial Dynamics, Oxidative Stress, and Neuroinflammation in D-Galactose-Induced Aging Rats.

Exercise and antioxidants have health benefits that improve cognitive impairment and may act synergistically. In this study, we examined the effects of treadmill exercise (TE) and mitochondria-targeted antioxidant mitoquinone (MitoQ), individually or combined, on learning and memory, mitochondrial dynamics, NADPH oxidase activity, and neuroinflammation and antioxidant activity in the hippocampus of D-galactose-induced aging rats. TE alone and TE combined with MitoQ in aging rats reduced mitochondrial fission factors (Drp1, Fis1) and increased mitochondrial fusion factors (Mfn1, Mfn2, Opa1). These groups also exhibited improved NADPH oxidase activity and antioxidant activity (SOD-2, catalase). TE or MitoQ alone decreased neuroinflammatory response (COX-2, TNF-α), but the suppression was greater with their combination. In addition, aging-increased neuroinflammation in the dentate gyrus was decreased in TE but not MitoQ treatment. Learning and memory tests showed that, contrarily, MitoQ alone demonstrated some similar effects to TE but not a definitive improvement. In conclusion, this study demonstrated that MitoQ exerted some positive effects on aging when used as an isolated treatment, but TE had a more effective role on cognitive impairment, oxidative stress, inflammation, and mitochondria dysfunction. Our findings suggest that the combination of TE and MitoQ exerted no synergistic effects and indicated regular exercise should be the first priority in neuroprotection of age-related cognitive decline.

Effects of treadmill exercise on the regulatory mechanisms of mitochondrial dynamics and oxidative stress in the brains of high-fat diet fed rats.

PURPOSE: The purpose of this study was to investigate the effects of treadmill exercise on oxidative stress in the hippocampal tissue and mitochondrial dynamic-related proteins in rats fed a long-term high-fat diet (HFD). METHODS: Obesity was induced in experimental animals using high fat feed, and the experimental groups were divided into a normal diet-control (ND-CON; n=12), a high fat diet-control (HFD-CON; n=12) and a high fat diet-treadmill exercise (HFD-TE; n=12) group. The rats were subsequently subjected to treadmill exercise (progressively increasing load intensity) for 8 weeks (5 min at 8 m/min, then 5 min at 11 m/min, and finally 20 min at 14 m/min). We assessed weight, triglyceride (TG) concentration, total cholesterol (TC), area under the curve, homeostatic model assessment of insulin resistance, and AVF/body weight. Western blotting was used to examine expression of proteins related to oxidative stress and mitochondrial dynamics, and immunohistochemistry was performed to examine the immunoreactivity of gp91phox. RESULTS: Treadmill exercise effectively improved the oxidative stress in the hippocampal tissue, expression of mitochondrial dynamic-related proteins, and activation of NADPH oxidase (gp91phox) and induced weight, blood profile, and abdominal fat loss. CONCLUSION: Twenty weeks of high fat diet induced obesity, which was shown to inhibit normal mitochondria fusion and fission functions in hippocampal tissues. However, treadmill exercise was shown to have positive effects on these pathophysiological phenomena. Therefore, treadmill exercise should be considered during prevention and treatment of obesity-induced metabolic diseases.

Resistance Exercise Improves Mitochondrial Quality Control in a Rat Model of Sporadic Inclusion Body Myositis.

BACKGROUND: Mitochondrial dysfunction is implicated in the pathogenesis of multiple muscular diseases, including sporadic inclusion body myositis (s-IBM), the most common aging-related muscle disease. However, the factors causing mitochondrial dysfunction in s-IBM are unknown. OBJECTIVE: We hypothesized that resistance exercise (RE) may alleviate muscle impairment by improving mitochondrial function via reducing amyloid-beta (Aß) accumulation. METHODS: Twenty-four male Wistar rats were randomized to a saline-injection control group (sham, n = 8), a chloroquine (CQ) control group (CQ-CON, n = 8), and a CQ plus RE group (CQ-RE, n = 8) in which rats climbed a ladder with weight attached to their tails 9 weeks after starting CQ treatment. RESULTS: RE markedly inhibited soleus muscle atrophy and muscle damage. RE reduced CQ-induced Aß accumulation, which resulted in decreased formation of rimmed vacuoles and mitochondrial-mediated apoptosis. Most importantly, the decreased Aß accumulation improved both mitochondrial quality control (MQC) through increased mitochondrial biogenesis and mitophagy, and mitochondrial dynamics. Furthermore, RE-mediated reduction of Aß accumulation elevated mitochondrial oxidative capacity by upregulating superoxide dismutase-2, catalase, and citrate synthase via activating sirtuin 3 signaling. CONCLUSION: RE enhances mitochondrial function by improving MQC and mitochondrial oxidative capacity via reducing Aß accumulation, thereby inhibiting CQ-induced muscle impairment, in a rat model of s-IBM.

Non-combative taekwondo evokes highly anaerobic physiological responses in elite-level athletes: potential evidence for a new training modality.

BACKGROUND: Despite the increasing international popularity of taekwondo (TKD) poomsae, there is a lack of physiological characterizations of elite-level competitors in the sport. Thus, the aim of the present study was to investigate the physiological demands associated with various types of TKD poomsae. METHODS: Eight male international TKD poomsae competitors carried out tae-geuk (TG) and professional (PF) poomsaes (in accordance with international competition standards), and consecutive TG (CTG) poomsae (a previously identified poomsae-specific training method). During each poomsae performance, oxygen uptake, heart rate, respiratory exchange ratio, and blood lactate were measured. The physiological responses were normalized and compared to maximal aerobic exercise tests such as a graded treadmill exercise (GXT) and maximal graded arm-crank ergometer exercise (ACE) to analyze the relative exercise intensity of each TKD poomsae. RESULTS: The results showed the relative exercise intensity of TG and PF poomsaes elicit moderate to high intensity physiological proportions of the maximal responses found during the GXT and ACE tests. Interestingly, CTG poomsae responses resulted in similar exercise intensities as those reported during high intensity interval training, indicating that CTG may be an effective training modality to improve aerobic and anaerobic exercise capacity while also utilizing and developing sport specific techniques and skills. CONCLUSIONS: This indicates the need for poomsae athletes to develop and maintain both aerobic and anaerobic capacity to enhance performance. Therefore, these physiological findings will help elite poomsae competitors and coaches to develop exercise programs of substantial duration and intensity to elicit beneficial performance adaptations.

Neuroprotective effect of treadmill exercise against blunted brain insulin signaling, NADPH oxidase, and Tau hyperphosphorylation in rats fed a high-fat diet.

Obesity induces oxidative stress by causing hyperglycemia and insulin resistance, while contributing to cognitive and memory decline by inducing insulin resistance in the brain and hyperphosphorylation of Tau proteins. We aimed to investigate the effects of treadmill exercise in improving these obesity-induced pathological phenomena. Sprague-Dawley rats aged 20 weeks were fed a high-fat diet (HFD) for 20 weeks to induce obesity. The rats were subsequently subjected to treadmill exercise (progressively increasing load intensity) for 8 weeks. The rats were divided into three groups: normal diet-control (n = 15), HFD-control (n = 15), and HFD-treadmill exercise (n = 15). We performed water maze and passive avoidance tests and assessed weight, area under the curve, homeostatic model assessment of insulin resistance, and abdominal visceral fat/body weight. Western blot was used to examine protein expression related to brain insulin signaling, tau hyperphosphorylation, and NADPH oxidase, and immunohistochemistry was performed to examine the immunoreactivity of p-Tau (Ser 202/Thr 205) and p22-phox. Treadmill exercise effectively rescued brain insulin signaling, hyperphosphorylation and aggregation of Tau protein, and NADPH oxidase activation in the high fat diet group. Furthermore, it improved insulin resistance inhibitors, decreased abdominal fat mass, inhibited weight gain, and rescued learning and memory. Obesity-induced insulin resistance contributes to cognitive decline, such as reduced learning and memory, but physical activity, such as treadmill exercise, was found to have a positive effect on brain function by improving thesepathological phenomena. Therefore, we suggest that treadmill exercise must be considered in the prevention and treatment of metabolic and neurodegenerative diseases.

Association of exercise-induced autophagy upregulation and apoptosis suppression with neuroprotection against pharmacologically induced Parkinson's disease.

PURPOSE: We investigated whether treadmill exercise (TE)-induced neuroprotection was associated with enhanced autophagy and reduced apoptosis in a mouse model of pharmacologically induced Parkinson's disease (PD). METHODS: PD was induced via the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). C57BL/6 male mice were randomly assigned to the following three groups: control (C57BL, n=10), MPTP with probenecid (MPTP/C, n=10), and MPTP/ C plus exercise (MPTP-TE, n=10). The MPTP-TE mice performed TE training (10 m/min, 60 min/day, 5 days/week) for 8 weeks. The rotarod test was used to assess motor function. RESULTS: TE restored MPTP/P-induced motor dysfunctionand increased tyrosine hydroxylase levels. Furthermore, TE diminished the levels of α-synuclein (α-syn), a neurotoxin; modulated the levels of autophagy-associated proteins, including microtubule-associated protein 1 light chain 3-II, p62, BECLIN1, BNIP3, and lysosomal-associated membrane protein-2, which enhanced autophagy; inhibited the activation of proapoptotic proteins (caspase-3 and BAX);and upregulated BCL-2, an antiapoptosis protein. CONCLUSION: Taken together, these results suggested that the TE-induced neuroprotection against MPTP-induced cell death was associated with enhanced autophagy and neuronal regeneration based on the findings of inhibited proapoptotic events in the brains of the TE-trained animals.

Neuroprotective effect of treadmill exercise possibly via regulation of lysosomal degradation molecules in mice with pharmacologically induced Parkinson's disease.

Dysfunction of mitophagy, which is a selective degradation of defective mitochondria for quality control, is known to be implicated in the pathogenesis of Parkinson's disease (PD). However, how treadmill exercise (TE) regulates mitophagy-related molecules in PD remains to be elucidated. Therefore, we aimed to investigate how TE regulates α-synuclein (α-syn)-induced neurotoxicity and mitophagy-related molecules in the nigro-striatal region of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mice. Our data showed that TE exhibited a significant restoration of tyrosine hydroxylase and motor coordination with suppression of α-syn expression, hallmarks of PD, possibly via up-regulation of lysosomal degradation molecules, LAMP-2 and cathepsin L, with down-regulation of p62, LC3-II/LC3-I ratio, PINK1 and parkin in the substantia nigra of MPTP mice. Therefore, these results suggest that treadmill exercise can be used as a non-invasive intervention to improve the pathological features and maintain a healthier mitochondrial network through appropriate elimination of defective mitochondria in PD.

Treadmill Exercise Attenuates α-Synuclein Levels by Promoting Mitochondrial Function and Autophagy Possibly via SIRT1 in the Chronic MPTP/P-Induced Mouse Model of Parkinson's Disease.

Accumulation of alpha-synuclein (α-Syn) is significantly correlated with the presence of progressive motor deficits, which is the main symptom of Parkinson's disease (PD). Although physical exercise reduces α-Syn levels, the molecular mechanisms by which physical exercise decreases α-Syn remain unclear. We hypothesized that treadmill exercise (TE) decreases α-Syn levels by improving mitochondrial function and promoting autophagy via the sirtuin-1 (SIRT1) signaling pathway in the chronic 1-methyl-1,2,3,6-tetrahydropyridine with probenecid (MPTP/P)-induced mouse model of PD. We found that TE reduces α-Syn levels, which subsequently ameliorates dopaminergic (DAergic) neuron loss and α-Syn-mediated apoptotic cell death. Most importantly, TE increases SIRT1 expression, which results in increased mitochondrial biogenesis and decreased oxidative stress by activating peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α). SIRT1 activation by TE also promotes autophagic clearance of α-Syn by inducing the activation of microtubule-associated protein 1 light chain 3 (LC3). Collectively, our results demonstrate that TE may reduce α-Syn levels by improving mitochondrial function and increasing autophagic flux, thereby ameliorating chronic MPTP/P-induced motor deficits in PD mice.

Treadmill exercise produces neuroprotective effects in a murine model of Parkinson's disease by regulating the TLR2/MyD88/NF-κB signaling pathway.

Parkinson's disease (PD) is characterized by progressive dopamine depletion and a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Treadmill exercise is a promising non-pharmacological approach for reducing the risk of PD and other neuroinflammatory disorders, such as Alzheimer's disease. The goal of this study was to investigate the effects of treadmill exercise on α-synuclein-induced neuroinflammation and neuronal cell death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Eight weeks of treadmill exercise improved motor deficits and reduced α-synuclein expression, a major causative factor of PD-like symptoms, in MPTP mice. Treadmill exercise also down-regulated the expression of toll-like receptor 2 and its associated downstream signaling molecules, including myeloid differentiation factor-88, tumor necrosis factor receptor-associated factor 6, and transforming growth factor-ß-activated protein kinase 1. These effects were associated with reduced ionized calcium-binding adapter molecule 1 expression, decreased IκBα and nuclear transcription factor-κB phosphorylation, decreased tumor necrosis factor α and interleukin-1ß expression, and decreased NADPH oxidase subunit expression in the SNpc and striatum. Additionally, it promoted the expression of tyrosine hydroxylase and the dopamine transporter, as well as plasma dopamine levels, in MPTP mice; these effects were associated with decreased caspase-3 expression and cleavage, as well as increased Bcl-2 expression in the SNpc. Taken together, our data suggest that treadmill exercise improves MPTP-associated motor deficits by exerting neuroprotective effects in the SNpc and striatum, supporting the notion that treadmill exercise is useful as a non-pharmacological tool for the management of PD.

Effect of Resistance Exercise on Muscle Metabolism and Autophagy in sIBM.

PURPOSE: Sporadic inclusion body myositis (sIBM), a muscular degenerative disease in the elderly, is an inflammatory myopathy characterized by muscle weakness in the wrist flexor, quadriceps, and tibialis anterior muscles. We aimed to identify the therapeutic effect of resistance exercise (RE) in improving sIBM symptoms in an sIBM animal model. METHODS: Six-week-old male Wistar rats were divided into a sham group (sham, n = 12), chloroquine-control group (CQ-con, n = 12), and chloroquine-RE group (CQ-RE, n = 12). The rats were subjected to 1 wk of exercise adaptation and 8 wk of exercise (three sessions per week). Protein expression was measured by Western blotting. Rimmed vacuoles (RV) were identified by hematoxylin and eosin staining and modified Gömöri trichrome staining, and amyloid deposition was examined by Congo red staining. RESULTS: The effects of CQ and RE differed depending on myofiber characteristics. Soleus muscles showed abnormal autophagy in response to CQ, which increased RV generation and amyloid-ß accumulation, resulting in atrophy. RE generated RV and decreased amyloid deposition in soleus muscles and also improved autophagy without generating hypertrophy. This reduced the atrophy signal transduction, resulting in decreased atrophy compared with the CQ-con group. Despite no direct effect of CQ, flexor hallucis longus muscles showed loss of mass because of reduced activity or increased inflammatory response; however, RE increased the hypertrophy signal, resulting in reduced autophagy and atrophy. CONCLUSIONS: These results demonstrate that RE had a preventive effect on sIBM induced by CQ treatment in an animal model. However, because the results were from an animal experiment, a more detailed study should be conducted over a longer period, and the effectiveness of different RE programs should also be investigated.

Treadmill exercise alleviates motor deficits and improves mitochondrial import machinery in an MPTP-induced mouse model of Parkinson's disease.

Alpha-synuclein (α-Syn) accumulation is significantly correlated with motor deficits and mitochondrial dysfunction in Parkinson's disease (PD), but the molecular mechanism underlying its pathogenesis is unclear. In this study, we investigated the effects of treadmill exercise on motor deficits and mitochondrial dysfunction in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD. Treadmill exercise inhibited dopaminergic neuron loss by promoting the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) and seemed to improve cell survival by reducing α-Syn expression. Most importantly, treadmill exercise increased expression of the mitochondrial import machinery proteins TOM-40, TOM-20, and TIM-23. This was associated with decreased α-Syn expression and subsequent upregulation of the mitochondrial proteins COX-I, COX-IV, and mtHSP70. Taken together, these results indicate that treadmill exercise may ameliorate motor deficits and improve mitochondrial dysfunction by reducing α-Syn expression in the MPTP-induced mouse model of PD.

Neuroprotective effects of endurance exercise against neuroinflammation in MPTP-induced Parkinson's disease mice.

Parkinson's disease (PD) is one of the main degenerative neurological disorders accompanying death of dopaminergic neurons prevalent in aged population. Endurance exercise (EE) has been suggested to confer neurogenesis and mitigate the degree of seriousness of PD. However, underlying molecular mechanisms responsible for exercise-mediated neuroprotection against PD remain largely unknown. Given the relevant interplay between elevated α-synuclein and neuroinflammation in a poor prognosis and vicious progression of PD and anti-inflammatory effects of EE, we hypothesized that EE would reverse motor dysfunction and cell death caused by PD. To this end, we chose a pharmacological model of PD (e.g., chronic injection of neurotoxin MPTP). Young adult male mice (7 weeks old) were randomly divided into three groups: sedentary control (C, n=10), MPTP (M, n=10), and MPTP + endurance exercise (ME, n=10). Our data showed that EE restored motor function impaired by MPTP in parallel with reduced cell death. Strikingly, EE exhibited a significant reduction in α-synuclein protein along with diminished pro-inflammatory cytokines (i.e., TNF-α and IL-1ß). Supporting this, EE prevented activation of Toll like receptor 2 (TLR2) downstream signaling cascades such as MyD88, TRAF6 and TAK-1 incurred by in MPTP administration in the striatum. Moreover, EE reestablished tyrosine hydroxylase at levels similar to C group. Taken together, our data suggest that an EE-mediated neuroprotective mechanism against PD underlies anti-neuroinflammation conferred by reduced levels of α-synuclein. Our data provides an important insight into developing a non-pharmacological countermeasure against neuronal degeneration caused by PD.

Treadmill exercise decreases amyloid-ß burden possibly via activation of SIRT-1 signaling in a mouse model of Alzheimer's disease.

Accumulation of amyloid-ß (Aß) correlates significantly with progressive cognitive deficits, a main symptom of Alzheimer's disease (AD). Although treadmill exercise reduces Aß levels, the molecular mechanisms underlying the effects are not fully understood. We hypothesize that treadmill exercise decreases Aß production and alleviates cognitive deficits by activating the non-amyloidogenic pathway via SIRT-1 signaling. Treadmill exercise improved cognitive deficits and alleviated neurotoxicity. Most importantly, treadmill exercise increased SIRT-1 level, which subsequently resulted in increased ADAM-10 level by down-regulation of ROCK-1 and upregulation of RARß, ultimately facilitating the non-amyloidogenic pathway. Treadmill exercise-induced activation in SIRT-1 level also elevated PGC-1α level and reduced BACE-1 and C-99 level, resulting in inhibition of the amyloidogenic pathway. Treadmill exercise may thus inhibit Aß production via upregulation of SIRT-1, which biases amyloid precursor protein processing toward the non-amyloidogenic pathway. This study provides novel and valuable insight into the molecular mechanisms possibly by which treadmill exercise reduces Aß production.

The effect of treadmill exercise on inflammatory responses in rat model of streptozotocin-induced experimental dementia of Alzheimer's type.

PURPOSE: The aim of this study was to investigate the effect of treadmill exercise on inflammatory response in streptozotocin (STZ)-induced animal model of Alzheimer's disease (AD). METHODS: To induce the animal model of AD, Sprague-Dawley rats were injected into intracerebroventricular (ICV) injection with 1.5 mg/kg of STZ. Rats were divided into three groups as Sham-con group (n = 7), STZ-con group (n = 7) and STZ-exe group (n = 7). Exercise group ran on the treadmill for 30 min/day, 5 days/week during 6 weeks. RESULTS: The results of this study were as follows: First, STZ-exe group was improved on cognitive function when compared to STZ-con group in water maze test. Second, STZ-exe group help reduce the expression level of amyloid-beta (Aß). In addition, Toll-like receptors-4 (TLR4), Nuclear factor-kB (NF-kB), Tumor necrosis factor-α (TNF-α) and Interleukin-1α (IL-1α) level of STZ-exe group was significantly decreased when compared to STZ-con group. CONCLUSION: These results show that treadmill exercise had positive effect on cognitive function and reduced inflammatory response in STZ-induced animal model of AD.