Study of the N1-(2,3,4-Trimethoxybenzyl)-N2-{2-[(2,3,4-Trimethoxybenzyl)Amine]Ethyl}-1,2-Ethandiamine Compound Effect on the Physical Performance of Animals.

We studied the effect of N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine (compound ALM-802) on the physical performance of mice after acute fatigue. The animals' performance was assessed on a treadmill. The criterion for assessing exercise tolerance was the length of the distance passed when running on a treadmill until complete fatigue. To assess the actoprotective activity of compound ALM-802, we used a method of stepwise increase in load with an initial running speed of 42 cm/sec and its subsequent increase by 5 cm/sec every 5 min. The maximum speed of movement of the treadmill belt is 77 cm/sec. Animals that received compound ALM-802 (2 mg/kg intraperitoneally), 1 day after acute fatigue, ran a distance to complete fatigue that exceeded that of control mice by 68% (387.9±60.5 and 230.6±29.6 m, respectively, p=0.023). The reference drug trimetazidine (30 mg/kg, intraperitoneally) did not have a significant effect on the distance traveled. Compound ALM-802 helps restore physical performance, i.e. exhibits significant actoprotective activity.

Accuracy of Kinovea-based kinematic gait analysis compared to a three-dimensional motion analysis system in healthy dogs.

OBJECTIVE: The goal of this study was to compare the accuracy of kinematic measurements obtained using the 2-D video-based kinematic motion analysis (KMA) software Kinovea (version 0.9.5; http://www.kinovea.org) with 3-D KMA in healthy dogs. METHODS: In this prospective study, 3-D marker-based KMA (VICON-Nexus, version 2.12.1, and Procalc, version 1.6; VICON Motion Systems Ltd) was performed on healthy dogs (body weight ≥ 20 kg; height at withers > 50 cm) walking on a treadmill (study period: November 2022). Simultaneously, dogs were video recorded by 1 smartphone (iPhone SE; Apple Inc) at a 1.50-m distance perpendicular to the shoulder (60 frames per second; 1,920 X 1,080 pixels) for KMA using Kinovea. Joint angle and joint angle velocity of the shoulder, elbow, carpus, hip, stifle, and tarsus were calculated for 6 synchronized gait cycles. Each gait cycle was divided into 10 increments. The difference between 3-D KMA and Kinovea was assessed for each parameter using robust linear mixed-effects models. RESULTS: 34 dogs were included. The estimated joint angle difference between 3-D KMA and Kinovea was less than 2° for all shoulder and elbow gait cycle increments. For the carpus, hip, stifle, and tarsus, the difference was less than 2° in 9, 5, 4, and 4 out of 10 gait cycle increments, respectively. CONCLUSIONS: Kinovea provides accurate kinematic data for the shoulder and elbow of healthy dogs. Carpal, hip, stifle, and tarsal kinematics were less accurate. CLINICAL RELEVANCE: The use of Kinovea for clinical and research purposes remains limited. Future Kinovea-based studies are needed to investigate the accuracy of carpal, hip, stifle, and tarsal kinematics.

Exploratory study of the lateral body sway predictability as frame of reference for gait rehabilitation following a total knee arthroplasty.

AIMS: The aim of the present study was to investigate whether the predictability of fronto-parallel trunk rotations (lateral body sway) could serve as a frame of reference to monitor recovery after total knee arthroplasty (TKA). METHODS: Before surgery, 11 TKA patients were asked to perform a treadmill walking task at three different speeds. In addition, their gait abilities were scored on three standard clinical walking tests. The treadmill walking task was repeated at three different timepoints following surgery, i.e., at 3, 6 and 12 months post-TKA. The movements of the trunk were digitized with an inertial sensor to capture the amplitude and the sample entropy (SEn) of the lateral body sway that were evaluated in separate ANOVAs. RESULTS: Before surgery the TKA group showed larger body sway (P = 0.025) with smaller SEn values (P = 0.038), which both restored to levels of healthy adults in the 12 months following surgery. Systematic correlations between the SEn values and the clinical test scores were found. CONCLUSIONS: The current findings show that movement behavior of the trunk in the fronto-parallel plane was affected by knee osteoarthritis and suggest that the predictability of the lateral body sway may serve as an index of recovery after TKA.

Treadmill exercise prevents recognition memory impairment in VD rat model and enhancement of hippocampal structural synaptic plasticity.

OBJECTIVE: In vascular dementia (VD), memory impairment caused by the damage of synaptic plasticity is the most prominent feature that afflicts patients and their families. Treadmill exercise has proven beneficial for memory by enhancing synaptic plasticity in animal models including stroke, dementia, and mental disorders. The aim of this study was to examine the effects of treadmill exercise on recognition memory and structural synaptic plasticity in VD rat model. METHODS: Male Sprague-Dawley rats were randomly assigned into four groups: control group (C group, n = 6), vascular dementia group (VD group, n = 6), treadmill exercise and vascular dementia group (Exe-VD group, n = 6), and treadmill exercise group (Exe group, n = 6). Four-week treadmill exercise was performed in the Exe-VD and Exe groups. Then, the common carotid arteries of rats in the VD and Exe-VD groups were identified to establish the VD model. Behavior tests (open-field test and novel recognition memory test) were adopted to evaluate anxiety-like behavior and recognition memory. Transmission electron microscopy and Golgi staining were performed to observe synaptic ultrastructure and spine density in the hippocampus. RESULTS: Our study demonstrated that VD rat exhibited significantly anxiety-like behavior and recognition impairment (p < .01), while treadmill exercise significantly alleviated anxiety-like behavior and improved recognition memory in VD rat (p < .01). Transmission electron microscopy revealed that hippocampal synapse numbers were significantly decreased in the VD group compared to the control group (p < .05). These alterations were reversed by treadmill exercise, and the rats exhibited healthier synaptic ultrastructure, including significantly increased synapse (p < .05). Meanwhile, golgi staining revealed that the spine numbers of the hippocampus were significantly decreased in the VD group compared to the control group (p < .05). When compared with the VD group, hippocampal spine numbers were significantly increased in the Exe-VD group (p < .05). CONCLUSION: The improvement of VD-associated recognition memory by treadmill exercises is associated with enhanced structural synaptic plasticity in VD rat model.

Moderate-intensity aerobic exercise enhanced dopamine signaling in diet-induced obese female mice without preventing body weight gain.

Obesity continues to rise in prevalence and financial burden despite strong evidence linking it to an increased risk of developing several chronic diseases. Dopamine response and receptor density are shown to decrease under conditions of obesity. However, it is unclear if this could be a potential mechanism for treatment without drugs that have a potential for abuse. Therefore, the aim of this study was to investigate whether moderate-intensity exercise could reduce body weight gain and the associated decreases in dopamine signaling observed with high-fat diet-induced adiposity. We hypothesized that exercise would attenuate body weight gain and diet-induced inflammation in high-fat (HF)-fed mice, resulting in dopamine signaling (release and reuptake rate) comparable to sedentary, low-fat (LF)-fed counterparts. This hypothesis was tested using a mouse model of diet-induced obesity (DIO) and fast-scan cyclic voltammetry to measure evoked dopamine release and reuptake rates. Although the exercise protocol employed in this study was not sufficient to prevent significant body weight gain, there was an enhancement of dopamine signaling observed in female mice fed a HF diet that underwent treadmill running. Additionally, aerobic treadmill exercise enhanced the sensitivity to amphetamine (AMPH) in this same group of exercised, HF-fed females. The estrous cycle might influence the ability of exercise to enhance dopamine signaling in females, an effect not observed in male groups. Further research into females by estrous cycle phase, in addition to determining the optimal intensity and duration of aerobic exercise, are logical next steps.

Differential expression of genes in the RhoA/ROCK pathway in the hippocampus and cortex following intermittent hypoxia and high intensity interval training.

Neuroplasticity is regulated by a balance of neurotrophic factors and inhibitory molecules that are permissive and restrictive to central nervous system (CNS) adaptation, respectively. Intermittent hypoxia (IH) and high intensity interval training (HIIT) are known to upregulate neurotrophic factors which are associated with improvements in learning and memory and greater functional recovery following CNS insults. We investigated whether the RhoA/ROCK signaling pathway (known to restrict neuroplasticity) is also modulated by IH and HIIT in the hippocampus, cortex, and lumbar spinal cord of male Wistar rats. The gene expression of 25 RhoA/ROCK signaling pathway components was determined following IH or IH combined with HIIT (30 minutes/day, five days/week, for six weeks). IH included ten three-minute bouts which alternated between hypoxia (15% O2) and normoxia. IH+HIIT synchronized the hypoxia protocol with treadmill training at speeds of 50 cm.s-1 during hypoxia, and 15 cm.s-1 during normoxia. In the hippocampus, IH and IH+HIIT significantly downregulated aggrecan and Nogo-receptor 2 mRNA which are involved in the inhibition of neuroplasticity. However, IH and IH+HIIT significantly upregulated genes including Lingo-1, Ncan, NgR3, and Sema4d in the cortex. This is the first time IH and HIIT have been linked to the modulation of plasticity inhibiting pathways. These results provide a fundamental step towards elucidating the interplay between the neurotrophic and inhibitory mechanisms involved in experience-driven neural plasticity which will aid in optimizing physiological interventions for the treatment of cognitive decline or neurorehabilitation.

Exercise training induces mild skeletal muscle adaptations without altering disease progression in a TDP-43 mouse model.

Exercise training is considered a non-pharmacological therapeutic approach for many diseases. Mild-to-moderate endurance exercise training is suggested to improve the mental and physical state of people with Amyotrophic Lateral Sclerosis (ALS). The aim of the present study was to determine the capacity of symptomatic rNLS8 mice, which develop ALS-reminiscent TAR DNA-binding protein 43 (TDP-43) pathology and motor dysfunction, to perform mild-to-moderate intensity treadmill exercise training and to evaluate the effects of this training on skeletal muscle health and disease progression. Symptomatic rNLS8 mice were able to complete four weeks of mild-to-moderate treadmill running (30 min at 6-13 m/min, 3 days a week). Exercise training induced an increase in the percentage of type IIA fibers in the tibialis anterior muscle as well as minor adaptations in molecular markers of myogenic, mitochondrial and neuromuscular junction health in some forelimb and hindlimb muscles. However, this exercise training protocol did not attenuate the loss in motor function or delay disease progression. Alternative exercise regimes need to be investigated to better understand the role exercise training may play in alleviating symptoms of ALS.

Physiological Adaptations to Progressive Endurance Exercise Training in Adult and Aged Rats: Insights from the Molecular Transducers of Physical Activity Consortium (MoTrPAC).

While regular physical activity is a cornerstone of health, wellness, and vitality, the impact of endurance exercise training on molecular signaling within and across tissues remains to be delineated. The Molecular Transducers of Physical Activity Consortium (MoTrPAC) was established to characterize molecular networks underlying the adaptive response to exercise. Here, we describe the endurance exercise training studies undertaken by the Preclinical Animal Sites Studies component of MoTrPAC, in which we sought to develop and implement a standardized endurance exercise protocol in a large cohort of rats. To this end, Adult (6-mo) and Aged (18-mo) female (n = 151) and male (n = 143) Fischer 344 rats were subjected to progressive treadmill training (5 d/wk, ∼70%-75% VO2max) for 1, 2, 4, or 8 wk; sedentary rats were studied as the control group. A total of 18 solid tissues, as well as blood, plasma, and feces, were collected to establish a publicly accessible biorepository and for extensive omics-based analyses by MoTrPAC. Treadmill training was highly effective, with robust improvements in skeletal muscle citrate synthase activity in as little as 1-2 wk and improvements in maximum run speed and maximal oxygen uptake by 4-8 wk. For body mass and composition, notable age- and sex-dependent responses were observed. This work in mature, treadmill-trained rats represents the most comprehensive and publicly accessible tissue biorepository, to date, and provides an unprecedented resource for studying temporal-, sex-, and age-specific responses to endurance exercise training in a preclinical rat model.

Effects of short-term dietary nitrate supplementation on exercise and coronary blood flow responses in patients with peripheral artery disease.

Background: Peripheral arterial disease (PAD) is a prevalent vascular disorder characterized by atherosclerotic occlusion of peripheral arteries, resulting in reduced blood flow to the lower extremities and poor walking ability. Older patients with PAD are also at a markedly increased risk of cardiovascular events, including myocardial infarction. Recent evidence indicates that inorganic nitrate supplementation, which is abundant in certain vegetables, augments nitric oxide (NO) bioavailability and may have beneficial effects on walking, blood pressure, and vascular function in patients with PAD. Objective: We sought to determine if short-term nitrate supplementation (via beetroot juice) improves peak treadmill time and coronary hyperemic responses to plantar flexion exercise relative to placebo (nitrate-depleted juice) in older patients with PAD. The primary endpoints were peak treadmill time and the peak coronary hyperemic response to plantar flexion exercise. Methods: Eleven PAD patients (52-80 yr.; 9 men/2 women; Fontaine stage II) were randomized (double-blind) to either nitrate-rich (Beet-IT, 0.3 g inorganic nitrate twice/day; BRnitrate) or nitrate-depleted (Beet-IT, 0.04 g inorganic nitrate twice/day, BRplacebo) beetroot juice for 4 to 6 days, followed by a washout of 7 to 14 days before crossing over to the other treatment. Patients completed graded plantar flexion exercise with their most symptomatic leg to fatigue, followed by isometric handgrip until volitional fatigue at 40% of maximum on day 4 of supplementation, and a treadmill test to peak exertion 1-2 days later while continuing supplementation. Hemodynamics and exercise tolerance, and coronary blood flow velocity (CBV) responses were measured. Results: Although peak walking time and claudication onset time during treadmill exercise did not differ significantly between BRplacebo and BRnitrate, the diastolic blood pressure response at the peak treadmill walking stage was significantly lower in the BRnitrate condition. Increases in CBV from baseline to peak plantar flexion exercise after BRplacebo and BRnitrate showed a trend for a greater increase in CBV at the peak workload of plantar flexion with BRnitrate (p = 0.06; Cohen's d = 0.56). Conclusion: Overall, these preliminary findings suggest that inorganic nitrate supplementation in PAD patients is safe, well-tolerated, and may improve the coronary hyperemic and blood pressure responses when their calf muscles are most predisposed to ischemia.Clinical trial registration:https://clinicaltrials.gov/, identifier NCT02553733.

Moderate aerobic training enhances the effectiveness of insulin therapy through hypothalamic IGF1 signaling in rat model of Alzheimer's disease.

Alzheimer's disease (AD) is a neurological condition that is connected with a decline in a person's memory as well as their cognitive ability. One of the key topics of AD research has been the exploration of metabolic causes. We investigated the effects of treadmill exercise and intranasal insulin on learning and memory impairment and the expression of IGF1, BDNF, and GLUT4 in hypothalamus. The animals were put into 9 groups at random. In this study, we examined the impact of insulin on spatial memory in male Wistar rats and analyzed the effects of a 4-week pretreatment of moderate treadmill exercise and insulin on the mechanisms of improved hypothalamic glucose metabolism through changes in gene and protein expression of IGF1, BDNF, and GLUT4. We discovered that rat given Aß25-35 had impaired spatial learning and memory, which was accompanied by higher levels of Aß plaque burden in the hippocampus and lower levels of IGF1, BDNF, and GLUT4 mRNA and protein expression in the hypothalamus. Additionally, the administration of exercise training and intranasal insulin results in the enhancement of spatial learning and memory impairments, the reduction of plaque burden in the hippocampus, and the enhancement of the expression of IGF1, BDNF, and GLUT4 in the hypothalamus of rats that were treated with Aß25-35. Our results show that the improvement of learning and spatial memory due to the improvement of metabolism and upregulation of the IGF1, BDNF, and GLUT4 pathways can be affected by pretreatment exercise and intranasal insulin.

Treadmill running on neuropathic pain: via modulation of neuroinflammation.

Neuropathic pain is a type of chronic pain caused by an injury or somatosensory nervous system disease. Drugs and exercise could effectively relieve neuropathic pain, but no treatment can completely stop neuropathic pain. The integration of exercise into neuropathic pain management has attracted considerable interest in recent years, and treadmill training is the most used among exercise therapies. Neuropathic pain can be effectively treated if its mechanism is clarified. In recent years, the association between neuroinflammation and neuropathic pain has been explored. Neuroinflammation can trigger proinflammatory cytokines, activate microglia, inhibit descending pain modulatory systems, and promote the overexpression of brain-derived neurotrophic factor, which lead to the generation of neuropathic pain and hypersensitivity. Treadmill exercise can alleviate neuropathic pain mainly by regulating neuroinflammation, including inhibiting the activity of pro-inflammatory factors and over activation of microglia in the dorsal horn, regulating the expression of mu opioid receptor expression in the rostral ventromedial medulla and levels of γ-aminobutyric acid to activate the descending pain modulatory system and the overexpression of brain-derived neurotrophic factor. This article reviews and summarizes research on the effect of treadmill exercise on neuropathic pain and its role in the regulation of neuroinflammation to explore its benefits for neuropathic pain treatment.

Cardiorespiratory Fitness Decreases High-Sensitivity C-Reactive Protein and Improves Parameters of Metabolic Syndrome.

AIM: To evaluate the relationship between cardiorespiratory fitness (CRF), expressed as maximal oxygen uptake (ml.kg-1.min-1), metabolic syndrome (MetS), and high-sensitivity C-reactive protein (hs-CRP), a marker of systemic inflammation. METHODS: The relationship between CRF, MetS, and hs-CRP was examined in a cohort of 173 men and women. CRF was evaluated using a Bruce protocol treadmill test and measured as estimated maximal oxygen uptake (VO2 max). Participants' physical activity status was self-reported. Plasma hs-CRP levels were measured using a standardized immunoassay, and the diagnostic criteria for MetS were based on guidelines established by the International Diabetes Federation (IDF). RESULTS: An inverse association was observed between hs-CRP levels and estimated VO2 max (p<0.01). Additionally, hs-CRP increased linearly with the number of MetS criteria present (p<0.01), while the estimated VO2 max decreased as the number of MetS criteria increased (p<0.01). Moreover, higher estimated VO2 max correlated with increased self-reported physical activity levels (p<0.01). Notably, participants engaging in two to three hours of exercise per week had hs-CRP levels ≤2.5 mg/L (p=0.018), considered a low-to-moderate risk range. CONCLUSION: Higher CRF, reflected by an estimated VO2 max, ≥45 ml/kg/min, is associated with lower hs-CRP levels and fewer MetS criteria. Additionally, regular physical activity, corresponding to higher VO2 max, appears to reduce systemic inflammation and ameliorate MetS risk factors. These findings support the mechanisms by which improved CRF and exercise may lower the risk of cardiovascular diseases (CVD) and type 2 diabetes (T2DM).

Magnetic Stimulation of Gigantocellular Reticular Nucleus with Iron Oxide Nanoparticles Combined Treadmill Training Enhanced Locomotor Recovery by Reorganizing Cortico-Reticulo-Spinal Circuit.

Background: Gigantocellular reticular nucleus (GRNs) executes a vital role in locomotor recovery after spinal cord injury. However, due to its unique anatomical location deep within the brainstem, intervening in GRNs for spinal cord injury research is challenging. To address this problem, this study adopted an extracorporeal magnetic stimulation system to observe the effects of selective magnetic stimulation of GRNs with iron oxide nanoparticles combined treadmill training on locomotor recovery after spinal cord injury, and explored the possible mechanisms. Methods: Superparamagnetic iron oxide (SPIO) nanoparticles were stereotactically injected into bilateral GRNs of mice with moderate T10 spinal cord contusion. Eight-week selective magnetic stimulation produced by extracorporeal magnetic stimulation system (MSS) combined with treadmill training was adopted for the animals from one week after surgery. Locomotor function of mice was evaluated by the Basso Mouse Scale, Grid-walking test and Treadscan analysis. Brain MRI, anterograde virus tracer and immunofluorescence staining were applied to observe the tissue compatibility of SPIO in GRNs, trace GRNs' projections and evaluate neurotransmitters' expression in spinal cord respectively. Motor-evoked potentials and H reflex were collected for assessing the integrity of cortical spinal tract and the excitation of motor neurons in anterior horn. Results: (1) SPIO persisted in GRNs for a minimum of 24 weeks without inducing apoptosis of GRN cells, and degraded slowly over time. (2) MSS-enabled treadmill training dramatically improved locomotor performances of injured mice, and promoted cortico-reticulo-spinal circuit reorganization. (3) MSS-enabled treadmill training took superimposed roles through both activating GRNs to drive more projections of GRNs across lesion site and rebalancing neurotransmitters' expression in anterior horn of lumbar spinal cord. Conclusion: These results indicate that selective MSS intervention of GRNs potentially serves as an innovative strategy to promote more spared fibers of GRNs across lesion site and rebalance neurotransmitters' expression after spinal cord injury, paving the way for the structural remodeling of neural systems collaborating with exercise training, thus ultimately contributing to the reconstruction of cortico-reticulo-spinal circuit.

Effects of different combinations of mechanical loading intensity, duration, and frequency on the articular cartilage in mice.

BACKGROUND: Understanding how healthy articular cartilage responds to mechanical loading is critical. Moderate mechanical loading has positive effects on the cartilage, such as maintaining cartilage homeostasis. The degree of mechanical loading is determined by a combination of intensity, frequency, and duration; however, the best combination of these parameters for knee cartilage remains unclear. This study aimed to determine which combination of intensity, frequency, and duration provides the best mechanical loading on healthy knee articular cartilage in vitro and in vivo. METHODS AND RESULTS: In this study, 33 male mice were used. Chondrocytes isolated from mouse knee joints were subjected to different cyclic tensile strains (CTSs) and assessed by measuring the expression of cartilage matrix-related genes. Furthermore, the histological characteristics of mouse tibial cartilages were quantified using different treadmill exercises. Chondrocytes and mice were divided into the control group and eight intervention groups: high-intensity, high-frequency, and long-duration; high-intensity, high-frequency, and short-duration; high-intensity, low-frequency, and long-duration; high-intensity, low-frequency, and short-duration; low-intensity, high-frequency, and long-duration; low-intensity, high-frequency, and short-duration; low-intensity, low-frequency, and long-duration; low-intensity, low-frequency, and short-duration. In low-intensity CTSs, chondrocytes showed anabolic responses by altering the mRNA expression of COL2A1 in short durations and SOX9 in long durations. Furthermore, low-intensity, low-frequency, and long-duration treadmill exercises minimized chondrocyte hypertrophy and enhanced aggrecan synthesis in tibial cartilages. CONCLUSION: Low-intensity, low-frequency, and long-duration mechanical loading is the best combination for healthy knee cartilage to maintain homeostasis and activate anabolic responses. Our findings provide a significant scientific basis for exercise and lifestyle instructions.

Research progress on the application of anti-gravity treadmill in the rehabilitation of Parkinson's disease patients: a mini review.

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by motor and non-motor symptoms. It is the second most common chronic progressive neurodegenerative disease. PD still lacks a known cure or prophylactic medication. Current treatments primarily address symptoms without halting the progression of PD, and the side effects of dopaminergic therapy become more apparent over time. In contrast, physical therapy, with its lower risk of side effects and potential cardiovascular benefits, may provide greater benefits to patients. The Anti-Gravity Treadmill is an emerging rehabilitation therapy device with high safety, which minimizes patients' fear and allows them to focus more on a normal, correct gait, and has a promising clinical application. Based on this premise, this study aims to summarize and analyze the relevant studies on the application of the anti-gravity treadmill in PD patients, providing a reference for PD rehabilitation practice and establishing a theoretical basis for future research in this area.

Multisensory Fusion Training and 7, 8-Dihydroxyflavone Improve Amyloid-ß-Induced Cognitive Impairment, Anxiety, and Depression-Like Behavior in Mice Through Multiple Mechanisms.

Background: There is growing interest in the role of physical activity in patients with of Alzheimer's disease (AD), particularly regarding its impact of cognitive function, gut microbiota, metabolites, and neurotrophic factors. Objective: To investigate the impact of multisensory fusion training (MSFT) combined with 7, 8-dihydroxyflavone (DHF) on the behavioral characteristics, protein expression, microbiome, and serum metabolome using the AD model in mice induced with amyloid-ß (Aß). Methods: We assessed cognitive ability, anxiety-like and depression-like behaviors in Aß mice using behavioral measures. Western blotting was employed to detect the expression of relevant proteins. The 16S rRNA gene sequencing and metabolomics were used to analyze changes in the intestinal microbial composition and serum metabolic profile, respectively, of Aß mice. Results: The behavioral outcomes indicated that a 4-week intervention combining DHF and MSFT yielded remarkable improvements in cognitive function and reduced anxiety and depression-like behaviors in Aß mice. In the hippocampus of Aß mice, the combined intervention increased the levels of BDNF, VGF, PSD-95, Nrf2, p-GSK3ß and p-CREB proteins. Analyses of sequence and metabolomic data revealed that Bacteroides and Ruminococcaceae were remarkably more abundant following the combined intervention, influencing the expression of specific metabolites directly linked to the maintenance of neuronal and neurobehavioral functions. These metabolites play a crucial role in vital processes, such as amino acid metabolism, lipid metabolism, and neurotransmitter metabolism in mice. Conclusion: Our study highlighted that MSFT combined with DHF improves cognitive impairment, anxiety, and depression-like behavior in Aß mice through multiple mechanisms, and further validated the correlation between the gut microbiome and serum metabolome. These findings open up a promising avenue for future investigations into potential treatment strategies for AD.

Interhemispheric inhibition and gait adaptation associations in people with multiple sclerosis.

BACKGROUND: Multiple sclerosis is a neurodegenerative disease that damages the myelin sheath within the central nervous system. Axonal demyelination, particularly in the corpus callosum, impacts communication between the brain's hemispheres in persons with multiple sclerosis (PwMS). Changes in interhemispheric communication may impair gait coordination which is modulated by communication across the corpus callosum to excite and inhibit specific muscle groups. To further evaluate the functional role of interhemispheric communication in gait and mobility, this study assessed the ipsilateral silent period (iSP), an indirect marker of interhemispheric inhibition and how it relates to gait adaptation in PwMS. METHODS: Using transcranial magnetic stimulation (TMS), we assessed interhemispheric inhibition differences between the more affected and less affected hemisphere in the primary motor cortices in 29 PwMS. In addition, these same PwMS underwent a split-belt treadmill walking paradigm, with the faster paced belt moving under their more affected limb. Step length asymmetry (SLA) was the primary outcome measure used to assess gait adaptability during split-belt treadmill walking. We hypothesized that PwMS would exhibit differences in iSP inhibitory metrics between the more affected and less affected hemispheres and that increased interhemispheric inhibition would be associated with greater gait adaptability in PwMS. RESULTS: No statistically significant differences in interhemispheric inhibition or conduction time were found between the more affected and less affected hemisphere. Furthermore, SLA aftereffect was negatively correlated with both average percent depth of silent period (dSP%AVE) (r = -0.40, p = 0.07) and max percent depth of silent period (dSP%MAX) r = -0.40, p = 0.07), indicating that reduced interhemispheric inhibition was associated with greater gait adaptability in PwMS. CONCLUSION: The lack of differences between the more affected and less affected hemisphere indicates that PwMS have similar interhemispheric inhibitory capacity irrespective of the more affected hemisphere. Additionally, we identified a moderate correlation between reduced interhemispheric inhibition and greater gait adaptability. These findings may indicate that interhemispheric inhibition may in part influence responsiveness to motor adaptation paradigms and the need for further research evaluating the neural mechanisms underlying the relationship between interhemispheric inhibition and motor adaptability.

Effect of Oleuropein on Anti-Obesity and Uncoupling Protein 1 Level in Brown Adipose Tissue in Mild Treadmill Walking Rats with Diet-Induced Obesity.

Oleuropein aglycone (OA), which is the absorbed form of oleuropein, is a major phenolic compound in extra virgin olive oil. We analyzed the anti-obesity effect of OA intake combined with mild treadmill walking (MTW, 4 m/min for 20 min/d, 5-6 d/wk, without electric shocks and slope) in rats under a high-fat diet (HF). Four-week-old male Sprague-Dawley rats (n=28) were equally divided into four groups: control (HF), 0.08% oleuropein-supplemented HF (HFO), HF with MTW (HF+W), and HFO with MTW (HFO+W) groups. After 28 d, the inguinal subcutaneous fat content and weight gain were significantly lower in the HFO+W group than in the control group. The HFO+W group also had significantly higher levels of urinary noradrenaline secretion, interscapular brown adipose tissue, uncoupling protein 1, brain transient receptor potential ankyrin subtype 1 (TRPA1), vanilloid subtype 1 (TRPV1), and brain-derived neurotrophic factor (BDNF) than the control group. Especially, the HFO+W group showed a synergistic effect on noradrenaline secretion. Therefore, OA combined with MTW may accelerate the enhancement of UCP1 and BDNF levels in rats with HF-induced obesity by increasing noradrenaline secretion after TRPA1 and TRPV1 activation.

Consistency of sex-based differences between treadmill and overground running using an inertial measurement unit (IMU).

Differences in running gait between treadmill and overground running has been subject of study, while consistency of group differences between running surfaces has not been previously analysed. This study examined both the differences between running surfaces and the consistency of sex-based differences between surfaces in some spatiotemporal and kinematic variables measured by an inertial measurement unit fastened over the lumbar spine. Thirty-two (sixteen females) endurance runners firstly performed overground and then treadmill (1 % inclination) runs at speeds between 9-21 km∙h-1. Males showed lower flight time (FT) [moderate effect size (ES)] during treadmill running compared to overground, while females showed greater stride frequency (SF) (moderate ES), lower stride length (SL) (moderate ES), FT (moderate ES), and vertical (VT) trunk displacement (moderate ES), as well as greater medio-lateral (ML) trunk displacement (moderate ES). No differences in CT between surfaces were found (trivial to small). Furthermore, all the sex-differences were consistent between treadmill and overground running: Males showed lower SF (large and moderate ES, respectively), greater SL (large and moderate ES) and CT (moderate and large ES), lower FT (large ES), greater VT displacement (moderate to large ES), and lower ML displacement (moderate ES) than females. These results may be of interest to carefully transfer the running gait analyses between surfaces depending on sex.

Synchronization of Neurophysiological and Biomechanical Data in a Real-Time Virtual Gait Analysis System (GRAIL): A Proof-of-Principle Study.

The investigation of gait and its neuronal correlates under more ecologically valid conditions as well as real-time feedback visualization is becoming increasingly important in neuro-motor rehabilitation research. The Gait Real-time Analysis Interactive Lab (GRAIL) offers advanced opportunities for gait and gait-related research by creating more naturalistic yet controlled environments through immersive virtual reality. Investigating the neuronal aspects of gait requires parallel recording of brain activity, such as through mobile electroencephalography (EEG) and/or mobile functional near-infrared spectroscopy (fNIRS), which must be synchronized with the kinetic and /or kinematic data recorded while walking. This proof-of-concept study outlines the required setup by use of the lab streaming layer (LSL) ecosystem for real-time, simultaneous data collection of two independently operating multi-channel EEG and fNIRS measurement devices and gait kinetics. In this context, a customized approach using a photodiode to synchronize the systems is described. This study demonstrates the achievable temporal accuracy of synchronous data acquisition of neurophysiological and kinematic and kinetic data collection in the GRAIL. By using event-related cerebral hemodynamic activity and visually evoked potentials during a start-to-go task and a checkerboard test, we were able to confirm that our measurement system can replicate known physiological phenomena with latencies in the millisecond range and relate neurophysiological and kinetic data to each other with sufficient accuracy.