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Exercise can reduce the incidence of stress-related mental diseases, such as depression and anxiety. Control group was neither exposed to CVMS nor TRE (noCVMS/noTRE). Females were tested and levels of serum17-beta-oestradiol (E2), estrogen receptors α immunoreactive neurons (ERα-IRs), estrogen receptors β immunoreactive neurons (ERβ-IRs) and oxytocin immunoreactive neurons (OT-IRs) were measured. The results showed there’s increased anxiety-like behaviors for mice from CVMS/noTRE, CVMS/higher speed TRE (CVMS/HTRE) and noCVMS/HTRE groups when they were put in open field and elevated maze tests. They had lower serum E2 levels than mice from CVMS/low-moderate speed TRE (CVMS/LMTRE), noCVMS/LMTRE and noCVMS/noTRE groups. The three groups of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice had more ERα-IRs and less ERβ-IRs in the medial preoptic area (mPOA), bed nucleus of the stria terminalis (BNST) and medial amygdala (MeA), hypothalamic paraventricular nucleus (PVN) and supraoptic nucleus (SON). The number of OT-IRs in PVN and SON of CVMS/noTRE, CVMS/HTRE and noCVMS/HTRE mice was also lower than that of mice from CVMS/LMTRE, noCVMS/LMTRE and noCVMS/noTRE groups. Interestingly, CVMS/LMTRE and noCVMS/LMTRE mice were similar to noCVMS/noTRE mice in that they did not show anxiety, while CVMS/HTRE and noCVMS/HTRE mice did not, which were similar to the mice in CVMS/noTRE. We propose that LMTRE instead of HTRE changes the serum concentration of E2. ERβ/ERα ratio and OT level in the brain may be responsible for the decrease in anxiety-like behavior in female mice exposed to anxiety-inducing stress conditions., Highlights • CVMS/LMTRE did not show anxiety. • noCVMS/LMTRE did not show anxiety. • ERβ/ERα ratio decreas anxiety. • OT decreas anxiety.

Yi Wang,1 Wenhua Li,1 Hongmei Zhang,1 Qingfeng Zhang,1 Geqi Ding,1 Zhiyu Guo,2 Yan Deng,1 Chunmei Li,1 Lixue Yin1 1Key Laboratory of Ultrasound in Cardiac Electrophysiology and Biomechanics of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2GE Cardiovascular Ultrasound Clinical & Research Department, Chengdu, People’s Republic of ChinaCorrespondence: Lixue YinKey Laboratory of Ultrasound in Cardiac Electrophysiology and Biomechanics of Sichuan Province, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, 32#, Xierduan, 1st Ring Road, Chengdu, People’s Republic of ChinaTel +86 18981838968Email yinlixue_cardiac@163.com; yinlixue8968@126.comPurpose: Left ventricular (LV) contractile reserve is commonly used for LV systolic function assessment, while data on normal LV contractile reserve to exercise and the effect of gender on it are contradictory and limited, especially in Chinese adults. The aims of the present study are to clarify echocardiographic normal reference of LV contractile reserve during treadmill exercise stress echocardiography in healthy Chinese adults and to evaluate the sex-specific impact on it.Patients and Methods: The study population consisted of 157 healthy Chinese adults. All subjects underwent comprehensive echocardiographic assessment at rest and immediately after a symptom-limited treadmill stress test. The impact of gender on LV contractile reserve was analyzed.Results: The study population consisted of 157 healthy Chinese adults. All subjects underwent comprehensive echocardiographic assessment at rest and immediately after a symptom-limited treadmill stress test. The impact of gender on LV contractile reserve was analyzed.Conclusion: Traditional LV contractile reserve of men was much higher than that of women in a healthy Chinese population. The difference might be because of higher BSA in men. ΔGLS was less influenced by METs and CI at rest compared to ΔEF. ΔGLS, and especially the ΔGLS index, might be considered as a more preferable contractile reserve parameter for clinical cardiac function evaluation.Keywords: stress echocardiography, treadmill stress test, left ventricular contractile reserve, longitudinal strain

This study was aimed to consider the effects of uphill (concentric, CON) and downhill (eccentric, ECC) treadmill exercise with Nano-BCAA supplementation on muscle protein expression of Akt and mTOR. Thirty aging male Wistar rats were randomly divided into 6 groups of (n = 5 each group): control (healthy), uphill running (CON, 0 to + 15°), downhill running (ECC, 0 to − 15°), Nano-BCAA (BCAA with Nano-Chitosan), CON + Nano-BCAA, and ECC + Nano-BCAA. The exercise training was performed in an interval form, with 3 sessions per weeks lasting 8 weeks. BCAA (in Nano form) administered by gavage 3 sessions per week for 8 weeks. RT-PCR was used to measure gene expression of Akt and mTOR. As well, protein expression of mTOR was performed by the IHC method. Administration of BCAA with CON and ECC increased the Akt gene expression (p

Physical exercise in humans induces changes in intraocular pressure, relating to the type and intensity of the workload. The purpose of the present study was to evaluate the variations in intraocular pressure and arterial blood pressure in dogs that underwent physical exercise on a treadmill. Thirty dogs were submitted to physical exercise consisting of walking (15 minutes), trotting (20 minutes), and walking (10 minutes). The intraocular pressure, blood pressure and pulse rate were recorded for each dog before starting the treadmill exercise, immediately after it ended, and after 20 minutes of passive recovery. Two-way repeated analysis of variance measurement showed the significant effect of treadmill exercise (P≤0.01) on intraocular pressure, pulse rate and diastolic blood pressure. No significant changes were observed to systolic blood pressure. Intraocular pressure and diastolic blood pressure decreased significantly during the passive recovery, and were strongly related. The pulse rate was significantly lower during the passive recovery. Although the mechanism determining the reduction in intraocular pressure during exercise remains not fully understood, our results suggest that it is strongly related to variations in arterial blood pressure.

Memory state of rat pups born to old and obese mother rats and the effect of a treadmill running of mother rats on the memory of rat pups were studied. The radial 8-arm maze test was performed to detect spatial learning memory, and the level of tumor necrosis factor-α, interleukin (IL)-1β, and IL-6 in the hippocampus was measured by enzymelinked immunoassay. Western blotting was performed for the expression of nuclear factor kappa-light-chain-enhancer (NF-κB), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IκB-α), B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), matrix metalloproteinase (MMP)-9, and immunohistochemistry for caspase-3 was conducted. The newborn rats were classified into following groups: pups born to old mother rats, pups born to old mother rats with exercise, pups born to old and obese mother rats, and pups born to old and obese mother rats with exercise. Exercise of mother ameliorated spatial learning memory impairment, inhibited proinflammatory cytokines production, NF-κB expression, and IκB-α phosphorylation of the pups born to old and obese mother rats. Maternal exercise suppressed Bax expression, the number of caspase-3, the level of MMP-9, and enhanced Bcl-2 expression of the pups born to old and obese mother rats. When the maternal exercise was performed, the impairment of spatial learning memory in pups was ameliorated. Therefore, it can be seen that exercise during pregnancy of older and obese mothers is an important factor in fetal health management.

The incidence of hypertension is continuously increasing. This study aimed to investigate the changes in clinical biochemical indexes of patients with heart failure with preserved ejection fraction (HFpEF), or patients with hypertensive heart disease (HHD) before and after treadmill exercise.Seventy-eight patients with HFpEF and 78 patients with HHD who were admitted to our hospital between February 2020 and February 2021 were selected to take a treadmill exercise test. All patients continued to exercise for 1 month. Clinical biochemical indexes [hemoglobin A1c (HbA1c), low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), total cholesterol (TC), N-segment pro-brain natriuretic peptide (NT-proBNP), and cardiac troponin I (cTnI)] were measured before and after the treadmill exercise test and compared between the two groups. Receiver operating characteristic (ROC) curves were drawn to analyze the optimal cutoff values of the clinical biochemical indexes in the diagnosis of HFpEF. The positive diagnostic rates of the biochemical indicators for HFpEF before and after treadmill exercise were compared using the optimal cut-off value of ROC as the positive standard.Before exercise, there was no significant difference in HbA1c, LDL-C, HDL-C, or TC between the two groups (P0.05), but NT-proBNP and cTnI were significantly higher in the HFpEF group than in the HHD group (P0.05). ROC curve analysis showed that before exercise, the best cutoff values for plasma NT-proBNP and cTnI in the diagnosis of HFpEF were 2,248.24 pg/mL and 1.14 ng/mL, respectively. After exercise, no significant difference was found in HbA1c, LDL-C, HDL-C, or TC between the two groups (P0.05). However, the levels of NT-proBNP and cTnI in both groups were higher after exercise, with more significant increases seen in the HFPEF group (P0.05). The positive rates of plasma NT-proBNP and cTnI in HFpEF group were statistically higher after exercise than before exercise (P0.05).The changes in plasma NT-proBNP and cTnI in patient after treadmill exercise can be used as sensitive indicators for the diagnosis and differentiation of HFpEF and HHD.

Age-induced apoptosis is believed to be caused by the imbalance between production of reactive oxygen species (ROS) and human body antioxidant defence. Regular aerobic treadmill-exercise has been suggested to enhance the antioxidant defence. This study aimed to investigate the effects of long-term treadmill exercise on age-related oxidative stress and the apoptosis of oligodendrocytes in the spinal cord of the rat. Sixty male rats were divided into six groups: three exercised groups, which underwent 6, 9 and 12 months of mild-to-moderate treadmill exercise and three non-exercised control groups. Spinal cord white or grey matter tissue sampling was done through mid-thoracic laminectomy. The malondialdehyde (MDA; indicator of oxidative stress) levels, the number of apoptotic oligodendrocytes and ultrastructural alterations were also evaluated. Our data showed that treadmill exercise resulted in decreased lipid peroxidation and the number of apoptotic oligodendrocytes in the spinal cord of rats, as compared to non-exercised animals. These results were confirmed by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) staining and electron microscope. This study suggests that the long-term treadmill exercise can affect oxidative stress and oligodendrocytes apoptosis in the spinal cord of aged rats and further studies are needed to validate these findings in humans.

Introduction: A sequence of time-dependent changes can affect the brain’s functional capacity. This study aimed at investigating the effects of Forced Aerobic Exercise (FAE) versus the Rosemary Extract (RE) on the learning abilities and oxidative stress modulation in rats. Methods: Young and old rats received daily FAE and RE for 3 months. Using the Passive Avoidance (PA) test, we evaluated the learning and memory of the rats by Step-Through Latency (STL) score. We measured the Superoxide Dismutase (SOD), Glutathione Peroxidase (GPx), Catalase (CATA), Malondialdehyde (MDA) enzymes levels, and Total Antioxidant Capacity (TAC) in the hippocampus Results: FAE could significantly increase the STL score (P

Prenatal stress causes learning deficits by inhibiting neurogenesis in the hippocampus. We studied the effects of maternal treadmill running or offspring treadmill running on the spatial learning ability of adolescent offspring rats or adult offspring rats born to maternal rats that received stress during pregnancy. For this study, spatial learning ability was measured by radial 8-arm maze task. Immunohistochemistry for 5-bromo-2'-deoxyuridine and Western blot for brain-derived neurotrophic factor (BDNF), tyrosine kinase B (TrkB), Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2) were also conducted. Stress was induced by exposing pregnant rats to hound in an enclosed room. Maternal treadmill running or treadmill running of offspring improved spatial learning ability of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Maternal treadmill running or treadmill running of offspring increased hippocampal cell proliferation of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Maternal treadmill running or treadmill running of offspring increased BDNF and TrkB expression in the hippocampus of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Maternal treadmill running or treadmill running of offspring inhibited Bax expression and increased Bcl-2 expression in the hippocampus of adolescent and adult offspring rats born to maternal rats receiving stress during pregnancy. Mother's exercise during pregnancy or child's exercise after childbirth can improve the spatial learning ability deteriorated due to stress during pregnancy.

Purpose Heat-and-moisture-exchanging devices (HME) are commonly used by endurance athletes during training in sub-zero environments, but their effects on performance are unknown. We investigated the influence of HME usage on running performance at − 15 °C. Methods Twenty-three healthy adults (15 male, 8 female; age 18–53 years; $$\dot{V}{\text O}_{2peak}$$ V ˙ O 2 p e a k men 56 ± 7, women 50 ± 4 mL·kg−1·min−1) performed two treadmill exercise tests with and without a mask-style HME in a randomised, crossover design. Participants performed a 30-min submaximal warm-up (SUB), followed by a 4-min maximal, self-paced running time-trial (TT). Heart rate (HR), respiratory frequency (fR), and thoracic area skin temperature (Tsk) were monitored using a chest-strap device; muscle oxygenation (SmO2) and deoxyhaemoglobin concentration ([HHb]) were derived from near-infra-red-spectroscopy sensors on m. vastus lateralis; blood lactate was measured 2 min before and after the TT. Results HME usage reduced distance covered in the TT by 1.4%, despite similar perceived exertion, HR, fR, and lactate accumulation. The magnitude of the negative effect of the HME on performance was positively associated with body mass (r2 = 0.22). SmO2 and [HHb] were 3.1% lower and 0.35 arb. unit higher, respectively, during the TT with HME, and Tsk was 0.66 °C higher during the HME TT in men. HR (+ 2.7 beats·min−1) and Tsk (+ 0.34 °C) were higher during SUB with HME. In the male participants, SmO2 was 3.8% lower and [HHb] 0.42 arb. unit higher during SUB with HME. Conclusion Our findings suggest that HME usage impairs maximal running performance and increases the physiological demands of submaximal exercise.

Maternal nutrition is necessary for the growth of the fetus, and excessive intake of nutrients interferes with brain development in offspring. In the current study, the effect of treadmill running during pregnancy in obese maternal rats on spatial learning memory and spatial working memory in rat pups was investigated. Phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), and extracellular signal-regulated kinase 1 and 2 (ERK1/2) was also identified in rat pups. Female rats were divided into the normal diet group and the high-fat diet group for 7 weeks, including pregnancy and lactation. Maternal treadmill running was performed for 4 weeks. The born rat pups were classified into a control group, a treadmill exercise group, a high-fat diet group, a high-fat diet and treadmill exercise group according to the status of maternal rats. Radial 8-arm maze task for spatial learning memory and Morris water maze task for spatial working memory were done. Western blot analysis was conducted to determine the expressions of PI3K, Akt, ERK1/2. In the current results, maternal treadmill running during pregnancy improved spatial learning memory and spatial working memory in rat pups born to obese maternal rats. This improving effect of memory was due to the enhanced phosphorylation of PI3K, Akt, and ERK1/2 by treadmill running.

Background Resting electrocardiogram (ECG) identification of long QT syndrome (LQTS) has limitations. Uncertainty exists on how to classify patients with borderline prolonged QT intervals. We tested if exercise testing could help serve to guide which children with borderline prolonged QT intervals may be gene positive for LQTS. Methods Pediatric patients (n = 139) were divided into three groups: Controls (n = 76), gene positive LQTS with borderline QTc (n = 21), and gene negative patients with borderline QTc (n = 42). Borderline QTc was defined between 440-470 (male) and 440-480 (female) ms. ECGs were recorded supine, sitting, and standing. Patients then underwent treadmill stress testing with Bruce protocol followed by a 9-minute recovery phase. Results Supine resting QTc, age, and Schwartz score for the three groups were: (a) gene positive: 446 ± 23 ms, 12.4 ± 3.4 years old, 3.2 ± 1.8; (b) gene negative: 445 ± 20 ms, 12.1 ± 2 years old, 2.0 ± 1.2; and (c) control: 400 ± 24 ms, 15.0 ± 3 years old. The three groups could be differentiated by their QTc response at two time points: standing and recovery phase at 6 minutes. Standing QTc ≥460 ms differentiated borderline prolonged QTc patients (gene positive and gene negative) from controls. Late recovery QTc ≥480 ms distinguished gene positive from gene negative patients. Conclusion Exercise stress testing can be useful to identify children who are gene positive borderline LQTS from a normal population and gene negative borderline QTc children, allowing for selective gene testing in a higher risk group of patients with borderline QTc intervals and intermediate Schwartz scores.

Maternal obesity is known to increase the likelihood of offspring becoming obese, high blood pressure, and other metabolic disorders. After inducing obesity, the effect of treadmill exercise in maternal rats during pregnancy on short-term memory was investigated in relation to neurogenesis in rat pups. Short-term memory was declined in rat pups born to obese maternal rats, and treadmill running during pregnancy alleviated short-term memory impairment in rat pups born to obese maternal rats. The number of doublecortin (DCX)-positive and 5-bro-mo-2'-deoxyuridine (BrdU)-positive cells in the hippocampal dentate gyrus was decreased in rat pups born to obese maternal rats. Treadmill running during pregnancy increased the number of DCX-positive and BrdU-positive cells in rat pups born to obese maternal rats. Expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB) in the hippocampus was decreased in the rat pups born to obese maternal rats. Treadmill running during pregnancy increased the expressions of BDNF and TrkB in rat pups born to obese maternal rats. Enhancing effect of short-term memory by treadmill exercise may be due to increased neurogenesis through activation of the BDNF-TrkB signaling pathway by treadmill exercise.

Context: Obesity is a major risk factor for chronic diseases. Abnormal changes in cardiovascular responses to exercise indicate the alteration in autonomic activity in obese. Aims: To assess and compare the cardiovascular parameters before and after exercise among obese and nonobese adult males. Subjects and Methods: Thirty each obese and normal-weight males between the age group 18-45 years were selected as cases and controls, respectively. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), corrected QT intervals were measured before and after submaximal treadmill exercise (QT and QTc) were done according to Bruce protocol. HR, SBP, DBP, MAP, QT, and QTc were also measured during passive recovery at 1 min and 5 min after exercise. Statistical Analysis Used: One-way analysis of variance and t-test were used to assess changes before and after exercise. Results: Resting HR was significantly higher in obese when compared to nonobese (P < 0.05). SBP, DBP, MAP, QT, and QTc were significantly higher in obese when compared to nonobese (P < 0.001). Immediately after exercise HR, SBP, DBP, MAP, QT, and QTc were significantly higher in obese when compared to nonobese (P < 0.001) 1 min after exercise. Conclusions: Obese individuals had elevated resting cardiovascular parameters and showed increased responses to steady exercise which could be due to alteration in autonomic functions with sympathetic hyperactivity. Delayed rate of decrease in HR and BP after exercise was also observed in obese, which indicates that they are at risk of developing cardiovascular diseases.

Introduction: This study evaluated the relationship between relative handgrip strenght index (rHGSi) as well as chronotropic response index (Cri) and heart rate recovery index (HRRi), which are the prognostic parameters of treadmill exercise. Patients and Methods: In total, 490 patients who were recommended to undergo the exercise electrocardiographic test were recruited in this study. The participants were divided into two groups based on both Cri (normal and low CRi groups) and rHGSi (high and low rHGSi groups). Results: The treadmill exercise time, peak heart rate, and metabolic equivalents were higher in the high rHGSi group than in the low rHGSi group. In addition, the 1st minute HRRi and Cri were higher in the high rHGSi group than in the low rHGSi group. The treadmill exercise time, basal and peak heart rate, metabolic equivalents, and 1st minute HRRi were significantly lower in the low CRi group than in the normal Cri group. rHGSi was considered an independent predictor of low chronotropic response index. Based on a bivariate analysis, a statistically significant positive correlation was observed between Cri and rHGSi. Similarly, there was a positive association between rHGSi and 1st minute HRRi. Conclusion: rHGSi might be a practical and effective tool in cardiovascular risk stratification., Giriş: Bu çalışmada, rölatif el kavrama gücü indeksi ile egzersiz testinin önemli prognostik belirteçleri olan kronotropik cevap indeksi ve kalp hızı toparlanma indeksi arasındaki ilişki araştırılmıştır. Hastalar ve Yöntem: Treadmill egzersiz testi planlanan 490 hasta çalışmaya alındı. Çalışma grubu el kavrama gücü indeksi ve kronotropik cevap indeksi değerlerine göre ayrı ayrı ikişer gruba ayrıldı. Bulgular: Yüksek rölatif el kavrama gücü indeksi grubunda, treadmill egzersiz zamanı, zirve kalp hızı ve metabolik ekivalan değeri düşük rölatif el kavrama gücü indeksi gruba kıyasla daha yüksek bulunmuştur. Ek olarak kronotropik cevap indeksi ve birinci dakika kalp hızı toparlanma indeksi gibi prognostik parametreler de yüksek rölatif el kavrama gücü indeksi grubunda daha yüksek bulunmuştur. Çalışma grubunu kronotropik cevap indeksine göre gruplandırıp incelediğimizde, treadmill egzersiz zamanı, bazal ve zirve kalp hızı, metabolik ekivalan ve birinci dakika ve kalp hızı toparlanma indeksi değerleri düşük kronotropik cevap indeksi grubunda yüksek kronotropik cevap indeksi gruba kıyasla daha düşük tespit edilmiştir. Ek olarak, rölatif el kavrama gücü indeksi düşük kronotropik cevap indeksinin bağımsız öngörücüsü olarak saptanmıştır. Yapılan çalışmada kronotropik cevap indeksi ve rölatif el kavrama gücü indeksi arasında pozitif korelasyon saptanmıştır. Aynı şekilde birinci dakika kalp hızı toparlanma indeksi ve rölatif el kavrama gücü indeksi arasında da istatistiksel olarak anlamlı derecede korelasyon saptanmıştır. Sonuç: Rölatif el kavrama gücü indeksi popülasyonda kardiyovasküler risk sınıflandırması için kullanışlı ve pratik bir araçtır.

Background Abnormal dynamics of QT intervals in response to sympathetic nervous system stimulation are used to diagnose long‐QT syndrome (LQTS). We hypothesized that parasympathetic stimulation with cold‐water face immersion following exercise would influence QT dynamics in patients with LQTS type 3 (LQT3). Methods Study participants (n = 42; mean age = 11.2 years) comprised 20 genotyped LQTS children and 22 healthy children. The LQTS group was divided into LQT3 (n = 12) and non‐LQT3 (n = 8) subgroups. Provocative testing for assessing QT dynamics comprised a treadmill exercise followed by cold‐water face immersion. The QT intervals were automatically measured at rest and during exercise, recovery, and cold‐water face immersion. The QT/heart rate (HR) relationship was visualized by plotting beat‐to‐beat confluence of the data. Results The QT/HR slopes, determined by linear regression analysis, were steeper in the LQTS group than in the control group during exercise and immersion tests: −2.16 ± 0.63 versus −1.21 ± 0.28, P

Introduction: Alzheimer’s disease is strongly correlated with learning and memory impairments. As exercise can enhance memory and learning, in this study, we have investigated the effects of treadmill exercise on memory impairment in amyloid β (Aβ)- treated rats focusing on brain-derived neurotrophic factor (BDNF) expression. Methods: Wistar male rats received intracerebroventricular (ICV) injection of Aβ and exercised on a treadmill for one month. Memory function was assessed using Morris water maze (MWM) and avoidance learning tasks. The level of BDNF was examined by the ELISA test. Results: The results of MWM and avoidance learning tasks showed that treadmill exercise could improve Aβ- induced memory impairment significantly. Moreover, BDNF expression increased following exercise in the Aβ- treated rats. Conclusion: The present results suggested that treadmill exercise may improve memory in Alzheimer’s disease by increasing BDNF level in the hippocampus.

The purpose of this study was to investigate the difference of emotional response, dopamine and lactate concentrations in moderate-intensity continuous exercise(MICE) and high-intensity interval exercise(HIIE)) according to with or without obesity. The subjects of this study were 30 adult males in their 20s and were divided into obesity group (OG, n=15) and non-obesity group (NOG, n=15). Treadmill exercise was performed with MICE (warm up for 5 minutes at 50% VT, exercise for time to consume 150㎉ at 90% VT, cool down for 5 minutes a t 50% VT) and HIIE ( repeated 5 t imes for 2 minutes at 115% VT, active recovery was repeated 4 times for 2 minutes at 85% VT). The results of the statistical analysis are as follows. MICE showed no difference in feeling scale between OG and NOF, and in HIIE, the feeling scale of OG was significantly negative compared to the NOG. In addition, the OG was more negative than the NOG in the PACES after exercise. Dopamine expression showed that both groups increased significantly after 10 minutes of exercise compared to before exercise in MICE and HIIE. At the concentration of lactate, the OG was significantly higher at the end of exercise than the NOG at HIIE.

Maternal separation during early life causes psychiatric and neurologi-cal disorders such as anxiety and depression. Depression or anxiety is closely associated with memory impairment. The purpose of this study was to investigate the effect of treadmill exercise on activity, short-term memory, vascular dysfunction using maternal separation-induced de-pression model. Maternal separation started on 15-day-old rats. The rats in the maternal separation and fluoxetine injection group received intraperitoneal injection of 5 mg/kg of fluoxetine one time daily for 15 days from 21 to 35 days. The rats performed treadmill exercise once a day during 15 days from 21 to 35 days. There was low activity and short-term memory was decreased in the maternal separation rats. Treadmill exercise and fluoxetine injection increased activity and ameliorated memory impairment. The number of rat endothelial cells antigen-1 (RECA-1) of microvessels was decreased in the maternal separation rats. The number of RECA-1was increased by treadmill exercise and fluoxetine injection. Expression of matrix metalloproteinase-9 (MMP-9) was increased and expressions of zonula occludens-2 (ZO-2) and oc-cludin were decreased in the maternal separation rats. Treadmill exer-cise and fluoxetine injection suppressed MMP-9 expression and en-hanced ZO-2 and occludin expressions in the maternal separation rats. The present study shows treadmill exercise and antidepressant treat-ment ameliorates depressive symptom and short-term memory impair-ment by protecting from blood-brain barrier damage.

Neuronal cell death in the hippocampus by cerebral ischemia causes disability of memory function. Cerebral ischemia also alters the expressions of brain-derived neurotrophic factor (BDNF), cyclic adenosine monophosphate-responsive element binding protein (CREB), extracellular signal-regulated protein kinase (ERK), and phosphatidylinositol 3-kinase/protein kinase B (Akt). In the present study, we investigated the effect of treadmill exercise on cerebral ischemia in relation with ERK-Akt-CREB-BDNF signaling pathway in the hippocampus using gerbils. Induction of cerebral ischemia deteriorated short-term memory with suppression of phosphorylation of ERK-Akt-CREB-BDNF pathway in the hippocampus of gerbils. Enhancement of apoptosis in the hippocampus was accompanied in the ischemia gerbils. Treadmill exercise improved short-term memory through enhancing phosphorylation of ERK-Akt-CREB-BDNF pathway with suppressing apoptosis in the hip-pocampus of the ischemia gerbils. The present results suggest that improvement of memory function after cerebral ischemia by treadmill exercise may be involved in the ERK-Akt-CREB-BDNF signaling pathway, resulting in inhibition of apoptosis in the hippocampus.

Purpose: Poloxamer-407 (P-407) is used to induce hyperlipidemia. Exercise is effective in improving arteriosclerosis and cognitive impairment. In this research, the effect of treadmill running on short-term memory in the P-407-treated hyperlipidemia rats was studied focusing on neuroinflammation.Methods: Rats were classified in normal group, normal and treadmill exercise group, P-407-treated group, and P-407-treated and treadmill exercise group. Hyperlipidemia rats were made by single intraperitoneal injection with P-407 (500 mg/kg). Treadmill exercise was conducted for 30 minutes once a day, 5 days per week during 28 days. Step-down avoidance task was done to measure short-term memory. Glial fibrillary acidic protein and ionized calcium binding adaptor molecule 1 were assessed by immunohistochemistry. Expression of adhesion molecules and proinflammatory cytokines was determined by western blot analysis.Results: Treadmill exercise alleviated lipid profiles in the P-407-induced hyperlipidemia rats. Treadmill exercise improved short-term memory, inhibited reactive astrogliosis and microglia activation, and suppressed expression of adhesion molecules and proinflammatory cytokines in the hyperlipidemic rats.Conclusions: Treadmill exercise exerts alleviating effect on memory deficits by inhibiting hippocampal neuroinflammation in the hyperlipidemia. The current results suggest that treadmill running serves as the treatment strategy for the cognitive dysfunction caused by hyperlipidemia.

Background: Exercise has been proven to be an effective therapy for stroke by reducing the microglia-initiated proinflammatory response. Few studies, however, have focused on the phenotypic changes in microglia cells caused by exercise training. The present study was designed to evaluate the influence of treadmill exercise on microglia polarization and the molecular mechanisms involved.Methods: Male Sprague-Dawley rats were randomly assigned into 3 groups: sham, MCAO and exercise. The middle cerebral artery occlusion (MCAO) and exercise groups received MCAO surgery and the sham group a sham operation. The exercise group also underwent treadmill exercise after the surgery. These groups were studied after 4 and 7 days to evaluate behavioral performance using a modified neurological severity score (mNSS), and infarct conditions using 2,3,5-triphenyl tetrazolium chloride. Quantitative real-time polymerase chain reaction (qRT-PCR) and Luminex was employed to determine the expressions of markers of microglia phenotypes. Western blotting was employed to identify the phosphorylation levels of Janus kinase1 (JAK1) and signal transducer and activator of transcription 6 (STAT6). Immunofluorescence was conducted to identify microglia phenotypes.Results: Treadmill exercise was found to improve neurobehavioral outcomes, mainly motor and balance functions, reduce infarct volumes and significantly increase interleukin-4 (IL-4) expression. In addition, treadmill exercise inhibited M1 microglia and promoted M2 microglia activation as evidenced by decreased M1 and increased M2 markers. Furthermore, an obvious increase in p-JAK1 and p-STAT6 was observed in the exercise group.Conclusions: Treadmill exercise ameliorates cerebral ischemia–reperfusion injury by enhancing IL-4 expression to promote M2 microglia polarization, possibly via the JAK1-STAT6 pathway.

BackgroundDespite the association of physical activity with improved cardiovascular outcomes and the association of high coronary artery calcification (CAC) scores with poor prognosis, elite endurance athletes have increased CAC. Yet, they nevertheless have better cardiovascular survival. We hypothesized that exercise may transform vascular calcium deposits to a more stable morphology.MethodsTo test this, hyperlipidemic mice (Apoe-/-) with baseline aortic calcification were separated into 2 groups (n = 9/group) with control mice allowed to move ad-lib while the exercise group underwent a progressive treadmill regimen for 9 weeks. All mice underwent blood collections and in vivo 18F-NaF μPET/μCT imaging both at the start and end of the exercise regimen. At euthanasia, aortic root specimens were obtained for histomorphometry.ResultsResults showed that, while aortic calcification progressed similarly in both groups based on µCT, the fold change in 18F-NaF density was significantly less in the exercise group. Histomorphometric analysis of the aortic root calcium deposits showed that the exercised mice had a lower mineral surface area index than the control group. The exercise regimen also raised serum PTH levels twofold.ConclusionThese findings suggest that weeks-long progressive exercise alters the microarchitecture of atherosclerotic calcium deposits by reducing mineral surface growth, potentially favoring plaque stability.

Purpose The purpose of this study was to investigate the effect of treadmill exercise and MitoQ treatment on NADPH oxidase, antioxidation and vascular function-related factors in aortic of D-galactose-induced aging rats. Methods To induce the animal model of aging, D-galactose was diluted in saline, and a dose of 100mg /kg was intraperitoneally injected into Sprague-Dawley rats once a day for a total of 10 weeks. Rats were divided into five groups: Control group (CON, n=9), D-galactose control group (DC, n=9), D-galactose+MitoQ group (DM, n=9), D-galactose+Exercise group (DE, n=9), D-galactose+MitoQ + Exercise group(DME, n=9), and treadmill exercise was conducted for 5 days/week during 8 weeks with gradual increase of intensity. MitoQ treatment was intraperitoneally injected at a concentration of 100μM/kg twice a week for 8 weeks during the research period. Results The result showed that treadmill exercise and MitoQ treatment decreased the expression of NADPH oxidase level and increased antioxidant enzyme such as SOD-2, catalase. It lead to positive effects such as increasing the level of eNOS, a protein involved in vascular function while decreasing the level of VCAM-1. In addition, as a result, it showed the structurally reduced intima-media thickness. Conclusions It can be concluded that treadmill exercise and MitoQ treatment are effective in ameliorating and treating vascular dysfunction resulting from aging.

Objective Recently, exergames have been used an exercise modality as aerobic fitness activities. However, evidence of its effectiveness on cardiovascular (CV)‐related risk factors remain unclear. Hypothesis We evaluate the effects of exergaming on CV‐related risk factors compared with traditional aerobic exercise in high CV risk patients. Methods Sixty‐five postmenopausal women with high CV risk were randomized among exergame (n = 22), treadmill (n = 22), and control (n = 21) groups. The exergame group was engaged in the running‐based exergame using Exer Heart and the treadmill group walked or jogged on a treadmill. Cardiorespiratory fitness, flow‐mediated dilation, endothelial progenitor cells (EPCs), epicardial fat thickness, metabolic parameters, and anthropometric parameters were measured in patients before and 12 weeks after the training. Results Exergaming significantly improved VO2 peak (P

Multiple treadmill-based studies using low numbers of horses have evaluated potential prophylactic treatments for exercise-induced pulmonary haemorrhage (EIPH) and found no effect. However, the relevance of these findings to racing is unclear. Because severity of EIPH incurred on treadmills has not been compared to that following high-speed racetrack exercise in the same horses, we retrospectively performed this comparison using bronchoalveolar lavage fluid red cell numbers (BALFRBC) due to the relative insensitivity of tracheobronchoscopy. Six race-fit Thoroughbreds with recent tracheobronchoscopic EIPH scores ≥2 were exercised to fatigue on a treadmill at 115% V̇O2max (5% incline, 12.3-14.2 m/s), and maximally on a racetrack over 800 m and 1,100 m with average speeds ranging from 16.4-16.7 and 15.5-16.6 m/s, respectively. Run order varied but was not randomised. Bronchoalveolar lavage (BAL) was performed blindly using Bivona tubes 45-60 mins post-exercise. BALFRBC were determined using a haemocytometer. Data were expressed as median and interquartile range, and analysed using RM ANOVA with significance set at P

Oxygen uptake (V̇O2), heart rate (HR), energy cost (EC) and oxygen pulse are lower during downhill compared to level or uphill locomotion. However, a change in oxygen pulse and EC during prolonged grade exercise is not well documented. This study investigated changes in cardiorespiratory responses and EC during 45-min grade exercises. Nine male healthy volunteers randomly ran at 75% HR reserve during 45-min exercise in a level (+1%), uphill (+15%) or downhill (−15%) condition. V̇O2 , minute ventilation (V̇E ) and end-tidal carbon dioxide (PetCO2) were recorded continuously with 5-min averaging between the 10th and 15th min (T1) and 40th and 45th min (T2). For a similar HR (157±3 bpm), V̇O2 , V̇E , and PetCO2 were lower during downhill compared to level and uphill conditions (p

PURPOSE This study is to investigate the effects of treadmill exercise on iron accumulation and microglial cell activity in the cerebral cortex of APP-C105 transgenic Alzheimer’s mice. METHODS The transgenic mice and their comparative non-transgenic mice at 24 months of age were divided into 3 groups: NTC (Non-Tg-Con, n=7), TC (Tg-Con, n=7), TE (Tg-Exe, n=7). TE group ran on the treadmill (30 min/day, 5 day/week) for 8 weeks. RESULTS The results show that treadmill exercise significantly improved spatial memory and cognitive function in TE group compared with TC group in Morris water-maze test and Passive avoidance test. In addition, TE group with treadmill exercise showed to decrease significantly in the accumulation level of iron, amyloid-beta protein, activated-microglia factor and pro-inflammation factor in comparison with TC group. anti-inflammation factor TE group was significantly increased than TC group. CONCLUSIONS These results suggest that treadmill exercise has positive effects on cognitive function, iron accumulation level of iron and activated-microglia factor and it can act as a key role for clinical strategy in AD.

BackgroundBone is a dynamically hierarchical material that can be divided into length scales of several orders of magnitude. Exercise can cause bone deformation, which in turn affects bone mass and structure. This study aimed to study the effects of treadmill running with different intensities on the long bone integrity and muscle biomechanical properties of adult male rats.MethodsForty-eight 5-month-old male SD rats were randomly divided into 4 groups: i.e., sedentary group (SED), exercise with speed of 12 m/min group (EX12), 16 m/min group (EX16), and 20 m/min group (EX20). The exercise was carried out for 30 min every day, 5 days a week for 4 weeks. The femurs were examined using three-point bending test, microcomputer tomography scanning and nanoindentation test; the soleus muscle was dissected for tensile test; ALP and TRACP concentrations were measured by serum analysis.ResultsThe failure load was significantly increased by the EX12 group, whereas the elastic modulus was not significantly changed. The microstructure and mineral densities of the trabecular and cortical bone were significantly improved by the EX12 group. The mechanical properties of the soleus muscle were significantly increased by treadmill exercise. Bone formation showed significant increase by the EX12 group. Statistically higher nanomechanical properties of cortical bone were detected in the EX12 group.ConclusionThe speed of 12 m/min resulted in significant changes in the microstructure and biomechanical properties of bone; besides, it significantly increased the ultimate load of the soleus muscle. The different intensities of treadmill running in this study provide an experimental basis for the selection of exercise intensity for adult male rats.

PURPOSE Impaired autophagy, a conserved process for the cellular energy homeostasis by degrading damaged cytosolic constituents, is an important contributor to the pathogenesis of atherosclerosis. The purpose of this study was to determine whether regular aerobic exercise can improve obesity-induced dysregulation of autophagy in mice arterial endothelial cells. METHODS High-fat diet-induced obese mice were subjected to the treadmill running for 10 weeks (15 m/min, 1 hour/day, 6 days/week). Endothelial cells were isolated from aorta by perfusing with QIAzol reagent. The mRNA and protein expressions of autophagy-related genes were investigated by qRT-PCR and western-blot respectively. Statistical analysis was performed by one-way ANOVA. RESULTS Autophagy-related gene expressions in both levels of mRNA and protein were significantly decreased in vascular endothelial cells and arterial vessels of obese mice. However, these phenomena have been partly reversed by the regular treatment of treadmill exercise for 10 weeks. Furthermore, eNOS downregulation induced by the obesity was also improved by the regular aerobic exercise, representing enhanced endothelial function. CONCLUSIONS The current study has shown that the obesity-induced autophagy dysregulation and vascular dysfunction can be partly improved by the regular aerobic exercise in mice vascular endothelial cells.

This study aimed to determine the effects of a single bout exercise on mitochondria-mediated apoptotic signaling in cardiac and skeletal muscles. Fischer 344 rats (4 months old) were randomly divided into the control or a single bout of exercise group (n=10 each). The rats performed a single bout of treadmill exercise for 60 min. Mitochondria-mediated apoptotic signaling (e.g., Bax, Bcl-2, mitochondrial permeability transition pore [mPTP] opening, cytochrome c, and cleaved caspase-3) was measured in cardiac (e.g., left ventricle) and skeletal (e.g., soleus and white gastrocnemius) muscles. A single bout of exercise significantly decreased mPTP opening sensitivity in all tissues. However, a single bout of exercise did not show any statistical differences in Bax, Bcl-2, cytochrome c, and cleaved caspase-3 in all tissues measured. A single bout of exercise did not show definite results on characteristics of mitochondria-mediated apoptotic signaling. Therefore, further research is necessary to provide a more mechanistic understanding of the apoptosis pathway.

BACKGROUND Hypertension usually accompanies the elevated sympathetic activity and sleep interruption. Few researches explored the dynamic changes and possible correlations in cardiovascular functions and sleep patterns during the development of hypertension. In contrast, exercise training provides several benefits on cardiovascular and sleep function in hypertensive subjects. However, controlling various factors during a long period of exercise training is difficult in hypertensive subjects, an animal model may be essential. This study aimed to explore dynamic changes in cardiovascular functions and sleep patterns during the development period of hypertension (10–20 weeks old) in spontaneously hypertensive rats (SHRs) and effects of exercise intervention. METHODS We used the treadmill exercise model for 8 weeks and started when SHRs were 12 weeks old. Electroencephalogram, electromyogram, electrocardiogram, and blood pressure (BP) were recorded simultaneously for 24 hours once a week over 11 weeks. RESULTS Untrained SHRs revealed the age-related increments in BP, and the significant increasing slopes of differences on BP and vascular sympathetic activity were observed during the development period of hypertension. Compared with untrained rats, age-related increases in BP and vascular sympathetic activity were significantly suppressed in trained SHRs. Nevertheless, trained SHRs showed more quiet sleep time at partial weeks. The positive correlation between the differences from 10 weeks of vascular sympathetic activity and BP was disappeared in trained SHRs. CONCLUSIONS There existed the significant correlation between the dynamic changes of vascular sympathetic activity and age-related elevation of BP during the development period of hypertension; however, exercise prevented hypertension and disrupted this correlation.

IntroductionChronotropic response with exercise is evaluated by peak heart rate (HR) achieved. Since most of the exercise-related chronotropic response occurs early after exercise is initiated, we investigated whether the HR achieved with a standard dose of exercise (Bruce stage 2) is associated with exercise capacity. We hypothesized that those with a blunted or disproportionate HR response at this exercise dose would have reduced exercise capacity compared to those with a typical HR response.Material and methodsWe reviewed 3,084 consecutive normal maximal treadmill stress echocardiographic reports acquired from individual adults over a 1.5-year period. We examined for association between stage 2 Bruce HR with age and sex-adjusted exercise capacity.ResultsAfter adjustment for age and sex, Bruce stage 2 HR was inversely associated ( = –0.08, p < 0.01) with exercise duration. Thus for every additional 10 beats per minute achieved in stage 2, exercise duration was generally shortened by about 45 s. Most of the subjects (92%) who had a stage 2 Bruce HR response below the 10th percentile had above average or average exercise capacity for their age and sex.ConclusionsLower Bruce stage 2 HR was associated with increased exercise capacity. Severely blunted HR response was associated with above average exercise capacity. Caution should therefore be exercised in attributing exercise intolerance to a blunted HR response when making a diagnosis of chronotropic incompetence.

The present study investigated whether treadmill exercise with bone marrow stromal cells (BMSCs) transplantation increase expression level of protein synthesis-related molecules in the soleus muscle after spinal cord injury (SCI). The spinal cord contusion injury was performed at the T9–10 level using the impactor (10 g×25 mm). BMSCs were cultured from femur and tibia of 4-week-old rats and then transplanted directly into the lesion 1-week post injury. The rats in exercise group were walking on treadmill device for 6 days per a week during 6 weeks. Prepared soleus muscles were used for examining mechanisms of protein synthesis after SCI. Myostatin induction level was increased by SCI, but BMSCs engrafting after SCI decreased compared to SCI group. Combination of treadmill exercise with BMSCs showed more potent decrement on myostatin expression. Protein kinase B (Akt) and mammalian target of rapamycin (mTOR) levels were significantly increased in SCI and BMSCs transplantation group compared to SCI group. Combination of treadmill exercise with BMSCs further facilitated expression levels of Akt and mTOR. Insulin-like growth factor-I (IGF-I) and phosphorylated cyclic adenosine monophosphate response element-binding protein (p-CREB) induction levels were more increased in SCI and BMSC transplantation group compared to SCI group. Combination of treadmill exercise with BMSCs further increased expression levels of IGF-I and p-CREB, although statistical significance was not appeared. Combining treadmill exercise with BMSCs transplantation might accelerate protein synthesis and hypertrophy in the soleus muscle after SCI through activation of IGF-I/mTOR signaling pathway.

Nicotine withdrawal symptoms comprise insomnia, depression, anxiety, attention disorders, and increased craving. We evaluated the ameliorating effect of treadmill exercise on nicotine withdrawal symptoms. The rats in the nicotine withdrawal groups received subcutaneous injection with 6-mg/kg nicotine hydrogen tartrate salt for 17 days. And then, the injection of nicotine hydrogen tartrate salt was stopped next for 2 weeks. The rats in the exercise groups performed treadmill running once a day, 5 days per week, for 31 days. In the present results, activity was decreased and anxiety-like behavior was observed in the nicotine withdrawal rats. Treadmill running increased activity and ameliorated anxiety-like behavior in the nicotine-withdrawal rats. Expressions of tryptophan hydroxylase (TPH) and 5-hydroxytryptamine (5-HT) in the dorsal raphe were decreased in the nicotine withdrawal rats, in contrast, treadmill running increased TPH and 5-HT expressions. Impaired short-term memory and deteriorated spatial learning ability were observed in the nicotine withdrawal rats, in contrast, treadmill running ameliorated impairment of short-term memory and spatial learning ability. Expressions of brain-derived neurotrophic factor and tyrosine kinase B (TrkB) were decreased in the nicotine withdrawal rats, in contrast, treadmill running increased brain-derived neurotrophic factor and TrkB expressions. The numbers of the doublecortin (DCX)-positive cells and 5-bromo-2'-deoxyuridine (BrdU)-positive cells in the dentate gyrus were suppressed in the nicotine withdrawal rats, in contrast, treadmill running enhanced the numbers of DCX-positive cells and BrdU-positive cells. The present study demonstrate that treadmill exercise ameliorated nicotine withdrawal-induced anxiety, depression, and memory impairment.

Background Bone tissue displays a hierarchical organization. Mechanical environments influence bone mass and structure. This study aimed to explore the effects of different mechanical stimuli on growing bone properties at macro–micro–nano scales. Methods Sixty five-week-old female Wistar rats were treadmill exercised at moderate intensity with the speed of 12 m/min, and then randomly divided into five groups according to weight-bearing level. After 8 weeks of experiment, femurs were harvested to perform multiscale tests. Results Bone formation was significantly increased by weight-bearing exercise, whereas bone resorption was not significantly inhibited. Trabecular and cortical bone mineral densities showed no significant increase by weight-bearing exercise. The microstructure of trabecular bone was significantly improved by 12% weight-bearing exercise. However, similar positive effects were not observed with further increase in weight-bearing levels. The nanomechanical properties of trabecular bone were not significantly changed by weight-bearing exercise. The macrostrength of whole femur and the nanomechanical properties of cortical bone significantly decreased in the 19% and 26% weight-bearing exercise groups. Conclusion When rats ran on the treadmill at moderate intensity during growth period, additional 12% weight-bearing level could significantly increase bone formation, improve microstructure of trabecular bone, as well as maintain the structure and mechanical properties of cortical bone. Excessive weight-bearing level caused no positive effects on the trabecular bone microstructure and properties of cortical bone at all scales. In addition, increased weight-bearing level exerted no significant influence on trabecular and cortical bone mineral densities.

PURPOSE This study was performed to investigate the effect of hypoxia in conjugation with endurance exercise training on skeletal muscle satellite cell activity in rats. METHODS Sprague-Dawley rats (20 weeks, N=21) were randomly divided into Control (Con, n=7), normoxia exercise (NE, n=7), and hypoxia exercise (HE, n=7) groups. Exercise training was performed on a rodent treadmill at a frequency of 5 days/week for 4 weeks, with gradual increases in exercise intensity. The rats were sacrificed 48 hours following the last exercise session. We conducted immunohistochemistry and western-blot for evaluating satellite cell cycle in phenotype and protein levels. RESULTS Any groups did not increase body weight, muscle weight and cross-sectional area were not increased in any groups after 4 weeks (p>.05). Satellite cell proliferation improved in NE (p=.001) and HE (p

NMN dampened exercise-induced benefits on glucose handling in diet-induced obesity. NMN administration alongside treadmill exercise enhanced the ratio of antioxidants to prooxidants. We suggest that NMN administration may not be beneficial when NAD+ levels are replete.

Purpose: Exercise is known to reduce proinflammatory cytokines production and apoptosis. We investigated the effect of treadmill running on spatial learning memory in terms of activation of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathway in Alzheimer disease (AD) rats. We also evaluated the effect of treadmill running on proinflammatory cytokine production and apoptosis.Methods: Using the stereotaxic frame, amyloid-β (Aβ) was injected into the lateral ventricle of the brain. The rats belong to treadmill running groups were forced to run on a motorized treadmill for 30 minutes per a day during 4 weeks, starting 3 days after Aβ injection. Morris water maze task was done for the determination of spatial learning memory. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, immunohistochemistry for cleaved caspase-3, and western blot for NF-κB, inhibitory protein of NF-κB (IκB), MAPK signaling pathway, tumor necrosis factor (TNF)-α, interleukin (IL)-1β were done.Results: Induction of AD increased proinflammatory cytokine secretion by activating the NF-κB/MAPK signaling pathway. These changes induced apoptosis in the hippocampus and reduced spatial learning memory. In contrast, treadmill running inactivated the NF-κB/MAPK signaling pathway and suppressed proinflammatory cytokine production. These changes inhibited apoptosis and improved spatial learning memory.Conclusions: Current results showed that treadmill running promoted spatial learning memory through suppressing proinflammatory cytokine production and apoptosis via inactivation of NF-κB/MAPK signaling pathway. Treadmill exercise can be considered an effective intervention for symptom relieve of AD.

Alzheimer's disease (AD) is associated with increased depression-related behaviours. Previous studies have reported a greater risk of AD and depression in women. In recent years, we and others have provided evidence that exercise during life could be used as a therapeutic strategy for stress-related disorders such as depression. The main goal of the current study was to determine whether treadmill exercise during life can reduce depression-related behaviours in male and female Wistar rats with sporadic Alzheimer-like disease (ALD). Animals were subjected to treadmill exercise eight weeks before and four weeks after ALD induction by streptozocin (STZ). We measured body weight, food intake, and depression-related symptoms in rats using five behavioural tests. We measured brain-derived-neurotrophic factor (BDNF), tumour-necrosis factor (TNF)-α, and interleukin (IL)-10 levels in the hippocampus and prefrontal cortex of animals. Our findings showed that exercise but not ALD induction decreased body weight and food intake in male and female rats. ALD induction increased depression-related symptoms and hippocampal TNF-α in male and female rats. Besides, treadmill exercise alone decreased depression-related behaviours and increased hippocampal BDNF in females but not males. We also found that treadmill exercise decreased depression-related behaviours and TNF-α in the hippocampus and prefrontal cortex, and increased IL-10 in the prefrontal cortex and BDNF in the hippocampus of female ALD-induced rats. However, treadmill exercise only reduced anhedonia-like behaviour and hippocampal TNF-α in male ALD-induced rats. Overall, the evidence from this study suggests that treadmill exercise alters depression-related behaviours, brain BDNF and cytokines in a sex-dependant manner in rats with sporadic Alzheimer-like disease.

The purpose of this study was to determine whether treadmill walking exercise can improve mechanical allodynia through regulation of Wnt/β-catenin signaling in dorsal root ganglion (DRG) neurons at the early stage of regeneration after sciatic nerve injury (SNI). The experimental rats were divided into seven groups: the normal control, sedentary groups for 3-, 7-, and 14-day post crush (dpc), and exercise group for 3, 7, and 14 dpc. The rats in exercise groups performed treadmill walking exercise at a speed of 8 m/min for 20 min once a day according to ex-periment duration. For evaluating neuropathic pain-like behavior after SNI, the mechanical allodynia was examined by von Frey apparatus. And the expression levels of pain-related protein were identified in the cytoplasm or nucleus of DRG neurons using Western blot techniques. Mechanical allodynia was significantly ameliorated in the exercise group at 7 and 14 dpc. Treadmill exercise further decreased Wnt3a ex-pression at 3, 7, and 14 dpc compared to in the sedentary group. Also, phosphorylated-low-density lipoprotein receptor 6 was decreased in exercise groups at 3 and 14 dpc. Beta-catenin was significantly de-creased in exercise groups at 3 and 14 dpc compared to sedentary groups as well as treadmill exercise decreased translocation of β-cat-enin towards the nucleus of DRG neurons at 14 dpc. Our findings indi-cate that treadmill walking exercise may be an important regulator of neuropathic pain after peripheral nerve injury through delayed Wnt/β-catenin signaling pathway in DRG neurons.