Treadmill Running Regulates Adult Neurogenesis, Spatial and Non-spatial Learning, Parvalbumin Neuron Activity by ErbB4 Signaling.

Exercise can promote adult neurogenesis and improve symptoms associated with schizophrenia and other mental disorders via parvalbumin (PV)-positive GABAergic interneurons in the dentate gyrus ErbB4 is the receptor of neurotrophic factor neuregulin 1, expressed mostly in PV-positive interneurons. Whether ErbB4 in PV-positive neurons mediates the beneficial effect of exercise and adult neurogenesis on mental disorder needs to be further investigation. Here, we first conducted a four-week study on the effects of AG1478, an ErbB4 inhibitor, on memory and neurogenesis. AG1478 significantly impaired the performance in several memory tasks, including the T-maze, Morris water maze, and contextual fear conditioning, downregulated the expression of total ErbB4 (T-ErbB4) and the ratio of phosphate-ErbB4 (p-ErbB4) to T-ErbB4, and associated with neurogenesis impairment. Interestingly, AG1478 also appeared to decrease intracellular calcium levels in PV neurons, which could be reversed by exercise. These results suggest exercise may regulate adult neurogenesis and PV neuron activity through ErbB4 signaling. Overall, these findings provide further evidence of the importance of exercise for neurogenesis and suggest that targeting ErbB4 may be a promising strategy for improving memory and other cognitive functions in individuals with mental disorders.

Peak fat oxidation, peak oxygen uptake, and running performance increase during pre-season in sub-elite male football players.

PURPOSE: In Football, the high-intensity running bouts during matches are considered decisive. Interestingly, recent studies showed that peak fat oxidation rates (PFO) are higher in football players than other athletes. This study aimed to investigate whether PFO increases following a pre-season. Secondarily, and due to COVID-19, we investigated whether PFO is related to the physical performance in a subgroup of semi-professional male football players. METHODS: Before and after 8 weeks of pre-season training, 42 sub-elite male football players (18 semi-professionals and 24 non-professionals) had a dual-energy x-ray absorptiometry scan and performed a graded exercise test on a treadmill for the determination of PFO, the exercise intensity eliciting PFO (Fatmax) and peak oxygen uptake (V̇O2peak). Additionally, the semi-professional players performed a Yo-Yo Intermittent Recovery Test level 2 (YYIR2) before and after pre-season training to determine football-specific running performance. RESULTS: PFO increased by 11 ± 10% (mean ± 95% CI), p = 0.031, and V̇O2peak increased by 5 ± 1%, p < 0.001, whereas Fatmax was unchanged (+12 ± 9%, p = 0.057), following pre-season training. PFO increments were not associated with increments in V̇O2peak (Pearson's r2 = 0.00, p = 0.948) or fat-free mass (FFM) (r2 = 0.00, p = 0.969). Concomitantly, YYIR2 performance increased in the semi-professional players by 39 ± 17%, p < 0.001, which was associated with changes in V̇O2peak (r2 = 0.35, p = 0.034) but not PFO (r2 = 0.13, p = 0.244). CONCLUSIONS: PFO, V̇O2peak, and FFM increased following pre-season training in sub-elite football players. However, in a subgroup of semi-professional players, increments in PFO were not associated with improvements in YYIR2 performance nor with increments in V̇O2peak and FFM.

Comparison of Concurrent and Asynchronous Running Kinematics and Kinetics From Marker-Based and Markerless Motion Capture Under Varying Clothing Conditions.

As markerless motion capture is increasingly used to measure 3-dimensional human pose, it is important to understand how markerless results can be interpreted alongside historical marker-based data and how they are impacted by clothing. We compared concurrent running kinematics and kinetics between marker-based and markerless motion capture, and between 2 markerless clothing conditions. Thirty adults ran on an instrumented treadmill wearing motion capture clothing while concurrent marker-based and markerless data were recorded, and ran a second time wearing athletic clothing (shorts and t-shirt) while markerless data were recorded. Differences calculated between the concurrent signals from both systems, and also between each participant's mean signals from both asynchronous clothing conditions were summarized across all participants using root mean square differences. Most kinematic and kinetic signals were visually consistent between systems and markerless clothing conditions. Between systems, joint center positions differed by 3 cm or less, sagittal plane joint angles differed by 5° or less, and frontal and transverse plane angles differed by 5° to 10°. Joint moments differed by 0.3 N·m/kg or less between systems. Differences were sensitive to segment coordinate system definitions, highlighting the effects of these definitions when comparing against historical data or other motion capture modalities.

Effects of treadmill exercise and chronic stress on anxiety-like behavior, neuronal activity, and oxidative stress in basolateral amygdala in morphine-treated rats.

The basolateral amygdala (BLA), which is sensitive to stress, is necessary for reward-seeking behavior and addiction. Regular exercise can produce various positive effects by affecting the BLA. Therefore, we aimed to investigate the effects of chronic stress and treadmill running (TR) on anxiety-like behavior, neuronal activity, lipid peroxidation (measured by malondialdehyde (MDA) levels, a marker for oxidative stress), and total thiol in BLA, in morphine-treated rats. Male Wistar rats were restricted in restraint stress and/or ran on the treadmill and treated with morphine (5 mg/kg) for 21 days. Anxiety-like behavior was evaluated using an elevated plus maze (EPM) and open field tests (OFTs), on day 22. On day 23, neuronal activity in BLA was assessed via single-unit recording. Finally, MDA and total thiol were assessed in BLA. Our results showed that chronic administration of morphine (5 mg/kg) did not affect anxiety-like behavior. However, the morphine-treated rats, subjected to chronic stress and exercise, showed fewer anxiety-like behaviors. Morphine increased BLA's MDA levels but it was prevented by TR. Glutamatergic and GABAergic basal neuronal activities were low in morphine-treated rats but after acute morphine application, there was a significant decrease in GABAergic neuronal activities in the morphine-exercise-stress (Mor-Exe-St) group. The results of this study showed that in morphine-treated rats, stress and exercise or their combination could have either co-directional or opposite effects to the chronic effects of morphine. These results indicate the existence of common pathways similar to endogenous opioids.

Hypoxia with or without Treadmill Exercises Affects Slow-Twitch Muscle Atrophy and Joint Destruction in a Rat Model of Rheumatoid Arthritis.

The effects of treadmill running under hypoxic conditions on joints and muscles of collagen-induced arthritis (CIA) rats were investigated. CIA rats were divided into normoxia no-exercise, hypoxia no-exercise (Hypo-no), and hypoxia exercise (Hypo-ex) groups. Changes were examined on days 2 and 44 of hypoxia with or without treadmill exercises. In the early stage of hypoxia, the expression of hypoxia-inducible factor (HIF)-1α increased in the Hypo-no and Hypo-ex groups. The expression of the egl-9 family hypoxia-inducible factor 1 (EGLN1) and vascular endothelial growth factor (VEGF) in the Hypo-ex group also increased. Under sustained hypoxia, the Hypo-no and Hypo-ex groups did not show increased expression of HIF-1α or VEGF, but p70S6K levels were elevated. Histologically, joint destruction was alleviated in the Hypo-no group, the loss of muscle weight in slow-twitch muscles was prevented, and muscle fibrosis was suppressed. In the Hypo-ex group, the preventive effect of a reduction in the slow-twitch muscle cross-sectional area was enhanced. Thus, chronic hypoxia in an animal model of rheumatoid arthritis controlled arthritis and joint destruction and prevented slow-twitch muscle atrophy and fibrosis. The combination of hypoxia with treadmill running further enhanced the preventive effects on slow-twitch muscle atrophy.

Reliability of Soft Tissue Vibration Measurement and Number of Steps Demanded during Treadmill Running.

The present study aims to determine the test-retest reliability of the input signal (INPUT) of foot impact and soft tissue vibration (STV) of the lower limb muscles during treadmill running. Twenty-six recreational runners participated in three running trials at constant velocity (10 km/h) within two days. The INPUT and STV of gastrocnemius medialis (GAS) and vastus lateralis (VL) were extracted from 100 steps measured by three triaxial accelerometers. The Intraclass Correlation Coefficient (ICC) was calculated to determine the Intra-trial and Inter-day reliability of the different variables. Intra-trial reliability results indicated that most of the INPUT and GAS STV parameters, except for damping coefficient and setting time, have good to excellent reliability (0.75 < ICC < 0.9) from the beginning of the run (10 steps) to the end. In contrast, only 4 VL STV parameters showed good reliability. Furthermore, inter-trial reliability measured on day one showed that the number of reliable parameters reduced, especially for VL STV, and more steps were required (20 < steps < 80) to achieve good reliability. Inter-day reliability results showed that only one VL STV parameter reached good reliability. Therefore, the present results show that the measurement of the foot impact and the calf muscle vibrations present a good to excellent reliability measured on a single trial and two trials carried out on the same day. The reliability of these parameters remains good when comparing two days of experimentation. We recommend measuring impact and STV parameters during treadmill running in the same session.

Treadmill running prevents atrophy differently in fast- versus slow-twitch muscles in a rat model of rheumatoid arthritis.

To investigate the effects of treadmill running on two different types of skeletal muscle, we established a rat model of collagen-induced arthritis (CIA). The skeletal muscles studied were the extensor digitorum longus (EDL), which is rich in fast-twitch muscle fibers, and the soleus, which is rich in slow-twitch muscle fibers. The histological and transcriptional changes in these muscles at 14 and 44 days after immunosensitization were compared between rats that were forced to exercise (CIA ex group) and free-reared CIA rats (CIA no group). Change in protein expression was examined on day 14 after a single bout of treadmill running. Treadmill running had different effects on the relative muscle weight and total and fiber cross-sectional areas in each muscle type. In the soleus, it prevented muscle atrophy. Transcriptional analysis revealed increased eukaryotic translation initiation factor 4E (Eif4e) expression on day 14 and increased Atrogin-1 and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) expression on day 44 in the soleus in the CIA ex group, suggesting an interaction between muscle type and exercise. A single bout of treadmill running increased the level of Eif4e and p70S6K and decreased that of Atrogin-1 in the soleus on day 14. Treadmill running prevented muscle atrophy in the soleus in a rat model of rheumatoid arthritis via activation of mitochondrial function, as evidenced by increased PGC-1α expression.

Moderate-intensity treadmill running relieves motion-induced post-traumatic osteoarthritis mice by up-regulating the expression of lncRNA H19.

BACKGROUND: The purpose of this study was to explore whether moderate-intensity exercise can alleviate motion-induced post-traumatic osteoarthritis (PTOA) and the expression change of lncRNA H19 during this progression. METHODS: Twenty-week-old male C57BL/6 mice were randomly divided into five groups: model control group (MC group, n = 6), treadmill model group (M group, n = 6), rehabilitation control group (RC group, n = 6), treadmill model + rehabilitation training group (M + R group, n = 6) and treadmill model + convalescent group (M + C group, n = 6). Paraffin sections were used to observe the pathological changes in the mouse knee joint in each group. A micro-CT was used to scan the knee joint to obtain the morphological indexes of the tibial plateau bone. Real-time PCR was used to detect the mRNA levels of inflammatory factors, synthetic and catabolic factors in cartilage. RESULTS: After high-intensity exercise for 4 weeks, the inflammation and catabolism of the mouse knee cartilage were enhanced, and the anabolism was weakened. Further study showed that these results were partially reversed after 4-week moderate-intensity training. The results of hematoxylin-eosin staining confirmed this finding. Meanwhile, high-intensity exercise reduced the expression of lncRNA H19 in cartilage, while the expression of lncRNA H19 increased after 4 weeks of moderate-intensity exercise. CONCLUSION: High-intensity treadmill running can cause injury to the knee cartilage in C57BL/6 mice which leads to PTOA and a decrease of lncRNA H19 expression in cartilage. Moderate-intensity exercise can relieve PTOA and partially reverse lncRNA H19 expression.

Quantitative and Qualitative Running Gait Analysis through an Innovative Video-Based Approach.

Quantitative and qualitative running gait analysis allows the early identification and the longitudinal monitoring of gait abnormalities linked to running-related injuries. A promising calibration- and marker-less video sensor-based technology (i.e., Graal), recently validated for walking gait, may also offer a time- and cost-efficient alternative to the gold-standard methods for running. This study aim was to ascertain the validity of an improved version of Graal for quantitative and qualitative analysis of running. In 33 healthy recreational runners (mean age 41 years), treadmill running at self-selected submaximal speed was simultaneously evaluated by a validated photosensor system (i.e., Optogait-the reference methodology) and by the video analysis of a posterior 30-fps video of the runner through the optimized version of Graal. Graal is video analysis software that provides a spectral analysis of the brightness over time for each pixel of the video, in order to identify its frequency contents. The two main frequencies of variation of the pixel's brightness (i.e., F1 and F2) correspond to the two most important frequencies of gait (i.e., stride frequency and cadence). The Optogait system recorded step length, cadence, and its variability (vCAD, a traditional index of gait quality). Graal provided a direct measurement of F2 (reflecting cadence), an indirect measure of step length, and two indexes of global gait quality (harmony and synchrony index). The correspondence between quantitative indexes (Cadence vs. F2 and step length vs. Graal step length) was tested via paired t-test, correlations, and Bland-Altman plots. The relationship between qualitative indexes (vCAD vs. Harmony and Synchrony Index) was investigated by correlation analysis. Cadence and step length were, respectively, not significantly different from and highly correlated with F2 (1.41 Hz ± 0.09 Hz vs. 1.42 Hz ± 0.08 Hz, p = 0.25, r2 = 0.81) and Graal step length (104.70 cm ± 013.27 cm vs. 107.56 cm ± 13.67 cm, p = 0.55, r2 = 0.98). Bland-Altman tests confirmed a non-significant bias and small imprecision between methods for both parameters. The vCAD was 1.84% ± 0.66%, and it was significantly correlated with neither the Harmony nor the Synchrony Index (0.21 ± 0.03, p = 0.92, r2 = 0.00038; 0.21 ± 0.96, p = 0.87, r2 = 0.00122). These findings confirm the validity of the optimized version of Graal for the measurement of quantitative indexes of gait. Hence, Graal constitutes an extremely time- and cost-efficient tool suitable for quantitative analysis of running. However, its validity for qualitative running gait analysis remains inconclusive and will require further evaluation in a wider range of absolute and relative running intensities in different individuals.

Physical exercise-induced thermoregulatory responses in trained rats: Effects of manipulating the duration and intensity of aerobic training sessions.

This study investigated the effects of increasing the intensity and/or duration of aerobic training sessions on thermoregulatory responses in rats subjected to exercises in temperate and warm environments. Thirty-two adult male Wistar rats were divided into four groups: a control (CON) group and three groups that were subjected to an 8-week aerobic training, during which the physical overload was achieved by predominantly increasing the exercise intensity (INT), duration (DUR) or by increasing both in an alternate manner (ID). During the last week of training, the rats received an abdominal sensor implant to measure their core body temperature (TCORE) by telemetry. After the training protocol, the 32 rats were subjected to incremental speed-exercises in temperate (23 °C) and warm (32 °C) environments. The rats had their TCORE recorded while running on a treadmill, and the ratio between the increase in TCORE and distance traveled was calculated to estimate thermoregulatory efficiency. All training protocols increased the rats' thermoregulatory efficiency during the incremental-speed exercise at 23 °C; i.e., trained rats attained faster running speeds but unchanged TCORE at fatigue compared to CON rats. However, none of the load components of training sessions - intensity or duration - was more effective than the other in improving this efficiency. At 32 °C, the aerobic training protocols did not influence the exercise-induced thermoregulatory responses. Our data indicate that different progressions in aerobic training performed at temperate conditions improved thermoregulatory efficiency during incremental exercise in the same environment; this training-induced adaptation was not clearly observed when running in warmer conditions.

Protection of DAergic neurons mediates treadmill running attenuated olfactory deficits and olfactory neurogenesis promotion in depression model.

In this study, we aimed to test the effects of treadmill running on depression induced olfactory functions and OB neurogenesis in depression model. Depression model was created with chronic unpredictable mild stress (CUMS) and treadmill running was performed as the antidepressant treatment. Behavioral results showed that treadmill running not only attenuated the depression mood but also improved the olfactory discrimination and sensitivity in CUMS depression model. Immune-staining further indicates treadmill running promoted neurogenesis in hippocampal OB region. Moreover, treadmill running prevented the loss of DAergic neurons in glomerular layer of OB region, indicating the critical role of DAergic neuronal functions in regulating treadmill running mediated olfactory functions. In depression model, inhibiting DAergic neurons by intra-OB injection of 6-OHDA resulted in the compromised improving effects of treadmill running olfactory discrimination. In conclusion, treadmill running could attenuate depression associated olfactory deficits by promoting olfactory neurogenesis and improve DAergic neural functions.

Acute physical exercise promotes the consolidation of emotional material.

Physical exercise can improve cognitive functions and promote learning and memory, especially when performed in close temporal proximity to the encoding of information. This benefit may occur due to circulating stress hormones released in response to acute exercise. When administered after encoding, acute stress typically enhances the consolidation of emotional stimuli. However, whether acute exercise also selectively modulates emotional memories remains to be explored. Likewise, the potential role of sex in moderating these effects has not been addressed so far. Here, we tested whether a single bout of aerobic exercise after learning boosts the consolidation and thus long-term memory for emotional versus neutral visuospatial stimuli. Healthy men and women learned an object-location task and subsequently were exposed to a vigorous-treadmill running task or control intervention. Memory was assessed 24 h later. Acute exercise significantly increased heart rate and salivary cortisol in both sexes and selectively facilitated the consolidation of emotional stimuli. In particular, we found improved memory for negative items in women and better recall of positive items in men following exercise exposure. This memory benefit was positively related to the increase in heart rate and cortisol in both men and women, suggesting that the favorable effects of acute exercise on emotional memory may be mediated via a co-activation of the sympathetic nervous system and the hypothalamus-pituitary-adrenocortical axis. Our findings thereby provide first evidence for the improvement of emotional memory consolidation by acute physical exercise that appears to rely on similar neuroendocrine mechanisms as psychosocial stressors. Given that exercise is healthy, cost-effective and practical in nature, it constitutes an ideal behavioral intervention strategy for boosting memory in clinical and educational settings alike.

Neuromuscular responses of the superficial quadriceps femoris muscles: muscle specific fatigue and inter-individual variability during severe intensity treadmill running.

OBJECTIVES: This study examined the time course of changes and patterns of responses in electromyographic amplitude (EMG AMP) and EMG mean power frequency (MPF) for the superficial quadriceps muscles during exhaustive treadmill runs within the severe exercise intensity zones (SIZ1 and SIZ2). METHODS: The EMG signals for the vastus lateralis (VL), rectus femoris (RF), and vastus medialis (VM) as well as times to exhaustion (Tlim) were recorded in ten runners during two exhaustive treadmill runs (SIZ1 and SIZ2). The composite and individual responses were compared among muscles and between intensities. RESULTS: The composite patterns of responses in EMG AMP (linear, quadratic, and cubic increases; r2/R2=0.684-0.848) and EMG MPF (linear, quadratic, and cubic decreases; r2/R2=0.648 - 0.852) for the VL and RF were consistent with neuromuscular fatigue in both zones, but those for the VM were not (quadratic, cubic, and non-significant relationships with responses near baseline). The RF tended to demonstrate greater fatigue (EMG MPF decreased from 80-100% Tlim). There was large inter-individual variability (only 10-60% of responses consistent with composite) in response to fatiguing treadmill running. CONCLUSIONS: The current findings support the examination and characterization of neuromuscular fatigue on an intensity, muscle, and subject-by-subject basis.

Time-course of running treadmill adaptation in novice treadmill runners.

Studies on running biomechanics and energetics are usually conducted on a treadmill. To ensure that locomotion on a treadmill is comparable to locomotion overground, participants need to be expert in the use of the device. This study aimed to identify the number and duration of sessions needed to obtain stable measurements for spatiotemporal and metabolic parameters in unexperienced treadmill runners. Fourteen male recreational runners performed three 15-min treadmill running trials in different days at a submaximal speed. Spatiotemporal and metabolic parameters were registered at minutes: 5, 10, 15 and their within-trial and between-trial changes were analysed using a two-way repeated measures ANOVA and Bonferroni post-hoc test. Within-trial differences were found in step frequency (decreased over time), Step Length and Contact Time (increased), reaching stability at different time points. Ventilator parameters increased, reaching stability after 5-10 min, while heart rate increased progressively over time. The only between-trial differences were an increase in step length and a decrease in step frequency at min 1, between trials 1 and 3. In conclusion, at least three running trials of 15 min are required to familiarize with the device. The last 5 min of the third trial can be regarded as stable measurements.

Frequent Carbohydrate Ingestion Reduces Muscle Glycogen Depletion and Postpones Fatigue Relative to a Single Bolus.

The timing of carbohydrate ingestion and how this influences net muscle glycogen utilization and fatigue has only been investigated in prolonged cycling. Past findings may not translate to running because each exercise mode is distinct both in the metabolic response to carbohydrate ingestion and in the practicalities of carbohydrate ingestion. To this end, a randomized, cross-over design was employed to contrast ingestion of the same sucrose dose either at frequent intervals (15 × 5 g every 5 min) or at a late bolus (1 × 75 g after 75 min) during prolonged treadmill running to exhaustion in six well-trained runners (V˙O2max 61 ± 4 ml·kg-1·min-1). The muscle glycogen utilization rate was lower in every participant over the first 75 min of running (Δ 0.51 mmol·kg dm-1·min-1; 95% confidence interval [-0.02, 1.04] mmol·kg dm-1·min-1) and, subsequently, all were able to run for longer when carbohydrate had been ingested frequently from the start of exercise compared with when carbohydrate was ingested as a single bolus toward the end of exercise (105.6 ± 3.0 vs. 96.4 ± 5.0 min, respectively; Δ 9.3 min, 95% confidence interval [2.8, 15.8] min). A moderate positive correlation was apparent between the magnitude of glycogen sparing over the first 75 min and the improvement in running capacity (r = .58), with no significant difference in muscle glycogen concentrations at the point of exhaustion. This study indicates that failure to ingest carbohydrates from the outset of prolonged running increases reliance on limited endogenous muscle glycogen stores-the ergolytic effects of which cannot be rectified by subsequent carbohydrate ingestion late in exercise.

The magnitude of physical exercise-induced hyperthermia is associated with changes in the intestinal permeability and expression of tight junction genes in rats.

We investigated whether the magnitude of exercise-induced hyperthermia influences intestinal permeability and tight junction gene expression. Twenty-nine male Wistar rats were divided into four groups: rest at 24 °C and exercise at 13 °C, 24 °C or 31 °C. The exercise consisted of a 90-min treadmill run at 15 m/min, and different ambient temperatures were used to produce distinct levels of exercise-induced hyperthermia. Before the experimental trials, the rats were treated by gavage with diethylenetriaminepentaacetic acid labeled with technetium-99 metastable as a radioactive probe. The rats' core body temperature (TCORE) was measured by telemetry. Immediately after the trials, the rats were euthanized, and the intestinal permeability was assessed by measuring the radioactivity of blood samples. The mRNA levels of occludin and zonula occludens-1 (ZO-1) genes were determined in duodenum samples. Exercise at 24 °C increased TCORE to values close to 39 °C, without changing permeability compared with the resting trial at the same environment. Meanwhile, rats' TCORE exceeded 40 °C during exercise at 31 °C, leading to greater permeability relative to those observed after exercise in the other ambient temperatures (e.g., 0.0037%/g at 31 °C vs. 0.0005%/g at 13 °C; data expressed as medians; p < 0.05). Likewise, the rats exercised at 31 °C exhibited higher mRNA levels of ZO-1 and occludin genes than the rats exercised at 24 °C or 13 °C. The changes in permeability and gene expression were positively and significantly associated with the magnitude of hyperthermia. We conclude that marked hyperthermia caused by exercise in the warmer environment increases intestinal permeability and mRNA levels of tight junction genes.

Forced Physical Training Increases Neuronal Proliferation and Maturation with Their Integration into Normal Circuits in Pilocarpine Induced Status Epilepticus Mice.

Increased number of newly-born neurons produced at latent stage after status epilepticus (SE) contribute to aberrant rewiring of hippocampus and are hypothesized to promote epileptogenesis. Although physical training (PT) was reported to cause further increase in neurogenesis after SE, how PT affect their integration pattern is still elusive, whether they integrate into normal circuits or increase aberrant integrations is yet to be determined. To understand this basic mechanism by which PT effects SE and to elaborate the possible role of neuronal integrations in prognosis of SE, we evaluated the effect of 4 weeks of treadmill PT in adult male mice after pilocarpine-induced SE on behavioral and aberrant integrations' parameters. Changes in BDNF gene methylation and its protein level in hippocampus was also measured at latent stage (2-weeks) to explore underlying pathways involved in increasing neurogenesis. Our results demonstrated that although PT increased proliferation and maturation of neurons in dentate gyrus, they showed reduced aberrant integrations into hippocampal circuitry assessed through a decrease in the number of ectopic granular cells, hilar basal dendrites and mossy fiber sprouting as compared to non-exercised SE mice. While SE decreased the percentage methylation of specific CpGs of BDNF gene's promoter, PT did not yield any significant difference in methylation of BDNF CpGs as compared to non-exercised SE mice. In conclusion, PT increases hippocampal neurogenesis through increasing BDNF levels by some pathways other than demethylating BDNF CpGs and causes post SE newly-born neurons to integrate into normal circuits thus resulting in decreased spontaneous recurrent seizures and enhanced spatial memory.

Treadmill Running in Established Phase Arthritis Inhibits Joint Destruction in Rat Rheumatoid Arthritis Models.

Exercise therapy inhibits joint destruction by suppressing pro-inflammatory cytokines. The efficacy of pharmacotherapy for rheumatoid arthritis differs depending on the phase of the disease, but that of exercise therapy for each phase is unknown. We assessed the differences in the efficacy of treadmill running on rheumatoid arthritis at various phases, using rat rheumatoid arthritis models. Rats with collagen-induced arthritis were used as rheumatoid arthritis models, and the phase after immunization was divided as pre-arthritis and established phases. Histologically, the groups with forced treadmill running in the established phase had significantly inhibited joint destruction compared with the other groups. The group with forced treadmill running in only the established phase had significantly better bone morphometry and reduced expression of connexin 43 and tumor necrosis factor α in the synovial membranes compared with the no treadmill group. Furthermore, few cells were positive for cathepsin K immunostaining in the groups with forced treadmill running in the established phase. Our results suggest that the efficacy of exercise therapy may differ depending on rheumatoid arthritis disease activity. Active exercise during phases of decreased disease activity may effectively inhibit arthritis and joint destruction.

Effects of mild running on substantia nigra during early neurodegeneration.

Moderate physical exercise acts at molecular and behavioural levels, such as interfering in neuroplasticity, cell death, neurogenesis, cognition and motor functions. Therefore, the aim of this study is to analyse the cellular effects of moderate treadmill running upon substantia nigra during early neurodegeneration. Aged male Lewis rats (9-month-old) were exposed to rotenone 1mg/kg/day (8 weeks) and 6 weeks of moderate treadmill running, beginning 4 weeks after rotenone exposure. Substantia nigra was extracted and submitted to proteasome and antioxidant enzymes activities, hydrogen peroxide levels and Western blot to evaluate tyrosine hydroxylase (TH), alpha-synuclein, Tom-20, PINK1, TrkB, SLP1, CRMP-2, Rab-27b, LC3II and Beclin-1 level. It was demonstrated that moderate treadmill running, practiced during early neurodegeneration, prevented the increase of alpha-synuclein and maintained the levels of TH unaltered in substantia nigra of aged rats. Physical exercise also stimulated autophagy and prevented impairment of mitophagy, but decreased proteasome activity in rotenone-exposed aged rats. Physical activity also prevented H2O2 increase during early neurodegeneration, although the involved mechanism remains to be elucidated. TrkB levels and its anterograde trafficking seem not to be influenced by moderate treadmill running. In conclusion, moderate physical training could prevent early neurodegeneration in substantia nigra through the improvement of autophagy and mitophagy.