Aß and tau prions feature in the neuropathogenesis of Down syndrome.

Down syndrome (DS) is caused by the triplication of chromosome 21 and is the most common chromosomal disorder in humans. Those individuals with DS who live beyond age 40 y develop a progressive dementia that is similar to Alzheimer's disease (AD). Both DS and AD brains exhibit numerous extracellular amyloid plaques composed of Aß and intracellular neurofibrillary tangles composed of tau. Since AD is a double-prion disorder, we asked if both Aß and tau prions feature in DS. Frozen brains from people with DS, familial AD (fAD), sporadic AD (sAD), and age-matched controls were procured from brain biorepositories. We selectively precipitated Aß and tau prions from DS brain homogenates and measured the number of prions using cellular bioassays. In brain extracts from 28 deceased donors with DS, ranging in age from 19 to 65 y, we found nearly all DS brains had readily measurable levels of Aß and tau prions. In a cross-sectional analysis of DS donor age at death, we found that the levels of Aß and tau prions increased with age. In contrast to DS brains, the levels of Aß and tau prions in the brains of 37 fAD and sAD donors decreased as a function of age at death. Whether DS is an ideal model for assessing the efficacy of putative AD therapeutics remains to be determined.

Familial Parkinson's point mutation abolishes multiple system atrophy prion replication.

In the neurodegenerative disease multiple system atrophy (MSA), α-synuclein misfolds into a self-templating conformation to become a prion. To compare the biological activity of α-synuclein prions in MSA and Parkinson's disease (PD), we developed nine α-synuclein-YFP cell lines expressing point mutations responsible for inherited PD. MSA prions robustly infected wild-type, A30P, and A53T α-synuclein-YFP cells, but they were unable to replicate in cells expressing the E46K mutation. Coexpression of the A53T and E46K mutations was unable to rescue MSA prion infection in vitro, establishing that MSA α-synuclein prions are conformationally distinct from the misfolded α-synuclein in PD patients. This observation may have profound implications for developing treatments for neurodegenerative diseases.

Plasma free metanephrine and normethanephrine levels correlated to plasma catecholamine after acute running in amateur runner.

BACKGROUND: Catecholamine is a typical index of exercise intensity, but it is difficult to detect. Plasma metanephrine (MN) and normethanephrine (NMN) levels are more stable than those of catecholamines. This study aimed to investigate plasma MN and NMN levels during acute exercise running in amateur runners. METHODS: Samples were collected from eight healthy male participants. They were either sedentary or running at low or high intensity for 30 min. Blood samples were collected under these conditions. Measurements taken included plasma adrenaline, noradrenaline, MN, and NMN. RESULTS: Plasma adrenaline levels increased after high-intensity exercise compared with sedentary subjects. Plasma noradrenaline, MN, and NMN levels increased after both low- and high-intensity exercise compared with sedentary subjects. In addition, these levels were also significantly higher at high intensity than at low intensity. Plasma adrenaline and noradrenaline levels were positively correlated with plasma free MN and NMN levels after acute running, respectively. CONCLUSION: This study revealed that plasma MN and NMN levels transiently increased depending on exercise intensity in amateur runners. In addition, plasma NMN levels are better markers than plasma MN levels because of their stronger correlation with plasma catecholamine levels.

Tau prions from Alzheimer's disease and chronic traumatic encephalopathy patients propagate in cultured cells.

Tau prions are thought to aggregate in the central nervous system, resulting in neurodegeneration. Among the tauopathies, Alzheimer's disease (AD) is the most common, whereas argyrophilic grain disease (AGD), corticobasal degeneration (CBD), chronic traumatic encephalopathy (CTE), Pick's disease (PiD), and progressive supranuclear palsy (PSP) are less prevalent. Brain extracts from deceased individuals with PiD, a neurodegenerative disorder characterized by three-repeat (3R) tau prions, were used to infect HEK293T cells expressing 3R tau fused to yellow fluorescent protein (YFP). Extracts from AGD, CBD, and PSP patient samples, which contain four-repeat (4R) tau prions, were transmitted to HEK293 cells expressing 4R tau fused to YFP. These studies demonstrated that prion propagation in HEK cells requires isoform pairing between the infecting prion and the recipient substrate. Interestingly, tau aggregates in AD and CTE, containing both 3R and 4R isoforms, were unable to robustly infect either 3R- or 4R-expressing cells. However, AD and CTE prions were able to replicate in HEK293T cells expressing both 3R and 4R tau. Unexpectedly, increasing the level of 4R isoform expression alone supported the propagation of both AD and CTE prions. These results allowed us to determine the levels of tau prions in AD and CTE brain extracts.

MSA prions exhibit remarkable stability and resistance to inactivation.

In multiple system atrophy (MSA), progressive neurodegeneration results from the protein α-synuclein misfolding into a self-templating prion conformation that spreads throughout the brain. MSA prions are transmissible to transgenic (Tg) mice expressing mutated human α-synuclein (TgM83+/-), inducing neurological disease following intracranial inoculation with brain homogenate from deceased patient samples. Noting the similarities between α-synuclein prions and PrP scrapie (PrPSc) prions responsible for Creutzfeldt-Jakob disease (CJD), we investigated MSA transmission under conditions known to result in PrPSc transmission. When peripherally exposed to MSA via the peritoneal cavity, hind leg muscle, and tongue, TgM83+/- mice developed neurological signs accompanied by α-synuclein prions in the brain. Iatrogenic CJD, resulting from PrPSc prion adherence to surgical steel instruments, has been investigated by incubating steel sutures in contaminated brain homogenate before implantation into mouse brain. Mice studied using this model for MSA developed disease, whereas wire incubated in control homogenate had no effect on the animals. Notably, formalin fixation did not inactivate α-synuclein prions. Formalin-fixed MSA patient samples also transmitted disease to TgM83+/- mice, even after incubating in fixative for 244 months. Finally, at least 10% sarkosyl was found to be the concentration necessary to partially inactivate MSA prions. These results demonstrate the robustness of α-synuclein prions to denaturation. Moreover, they establish the parallel characteristics between PrPSc and α-synuclein prions, arguing that clinicians should exercise caution when working with materials that might contain α-synuclein prions to prevent disease.

Propagation of prions causing synucleinopathies in cultured cells.

Increasingly, evidence argues that many neurodegenerative diseases, including progressive supranuclear palsy (PSP), are caused by prions, which are alternatively folded proteins undergoing self-propagation. In earlier studies, PSP prions were detected by infecting human embryonic kidney (HEK) cells expressing a tau fragment [TauRD(LM)] fused to yellow fluorescent protein (YFP). Here, we report on an improved bioassay using selective precipitation of tau prions from human PSP brain homogenates before infection of the HEK cells. Tau prions were measured by counting the number of cells with TauRD(LM)-YFP aggregates using confocal fluorescence microscopy. In parallel studies, we fused α-synuclein to YFP to bioassay α-synuclein prions in the brains of patients who died of multiple system atrophy (MSA). Previously, MSA prion detection required ∼120 d for transmission into transgenic mice, whereas our cultured cell assay needed only 4 d. Variation in MSA prion levels in four different brain regions from three patients provided evidence for three different MSA prion strains. Attempts to demonstrate α-synuclein prions in brain homogenates from Parkinson's disease patients were unsuccessful, identifying an important biological difference between the two synucleinopathies. Partial purification of tau and α-synuclein prions facilitated measuring the levels of these protein pathogens in human brains. Our studies should facilitate investigations of the pathogenesis of both tau and α-synuclein prion disorders as well as help decipher the basic biology of those prions that attack the CNS.

Aß and Tau Prions Causing Alzheimer's Disease.

Studies show that patients with Alzheimer's disease (AD) have both Aß and tau prions, and thus, AD is a double-prion disease. AD patients with the greatest longevity exhibited low levels of both Aß and tau prions; tau prions were nearly absent in the brains of almost half of the patients who lived beyond 80 years of age. Using cellular bioassays for prions in postmortem samples, we found that both Aß and tau proteins misfold into prions leading to AD, which is either a sporadic or familial dementing disorder. Although AD is transmissible experimentally, there is no evidence that AD is either communicable or contagious. Since the progression of AD correlates poorly with insoluble Aß in the central nervous system (CNS), it was difficult to distinguish between inert amyloids and Aß prions. To measure the progression of AD, we devised rapid bioassays to measure the abundance of isoform-specific Aß prions in the brains of transgenic (Tg) mice and in postmortem human CNS samples from AD victims and people who died of other neurodegenerative diseases (NDs). We found significant correlations between the longevity of individuals with AD, sex, and genetic background, despite the fact that all postmortem brain tissue had essentially the same confirmed neuropathology.Although brains from all AD patients had measurable levels of Aß prions at death, the oldest individuals had lower Aß prion levels than the younger ones. Additionally, the long-lived individuals had low tau prion levels that correlated with the extent of phosphorylated tau (p-tau). Unexpectedly, a longevity-dependent decrease in tau prions was found in spite of increasing amounts of total insoluble tau. When corrected for the abundance of insoluble tau, the tau prion levels decreased exponentially with respect to the age at death with a half-time of approximately one decade, and this correlated with the abundance of phosphorylated tau.Even though our findings with tau prions were not unexpected, they were counterintuitive; thus, tau phosphorylation and tau prion activity decreased exponentially with longevity in patients with AD ranging from ages 37 to 99 years. Our findings demonstrated an inverse correlation between longevity in AD patients and the abundance of neurotoxic tau prions. Moreover, our discovery may have profound implications for the selection of phenotypically distinct patient populations and the development of diagnostics and effective therapeutics for AD.

CSF1R inhibitors induce a sex-specific resilient microglial phenotype and functional rescue in a tauopathy mouse model.

Microglia are central to pathogenesis in many neurological conditions. Drugs targeting colony-stimulating factor-1 receptor (CSF1R) to block microglial proliferation in preclinical disease models have shown mixed outcomes, thus the therapeutic potential of this approach remains unclear. Here, we show that CSF1R inhibitors given by multiple dosing paradigms in the Tg2541 tauopathy mouse model cause a sex-independent reduction in pathogenic tau and reversion of non-microglial gene expression patterns toward a normal wild type signature. Despite greater drug exposure in male mice, only female mice have functional rescue and extended survival. A dose-dependent upregulation of immediate early genes and neurotransmitter dysregulation are observed in the brains of male mice only, indicating that excitotoxicity may preclude functional benefits. Drug-resilient microglia in male mice exhibit morphological and gene expression patterns consistent with increased neuroinflammatory signaling, suggesting a mechanistic basis for sex-specific excitotoxicity. Complete microglial ablation is neither required nor desirable for neuroprotection and therapeutics targeting microglia must consider sex-dependent effects.

A Study of Race Pacing in the Running Leg of the Japan University Triathlon Championship.

Choosing an appropriate pacing strategy is important for good triathlon performance. In the Japan Student Triathlon Championship held in 2020, the men's category was divided into two groups, which was a different racing style from the previous races that all athletes start at the same time. It is highly likely that the performance level will vary as grouping was performed according to the competence of each player. The aim of this study was to understand the relationship of the total time and time of each leg between the superior performance group and the inferior performance group, as well as the difference in pacing during running in participants of the 2020 Japan University Triathlon Championship Watarase Competition, which was held under unconventional conditions. We analyzed 153 male athletes (Group A: 77; Group B: 76) who completed the race. The total race time, leg time, and average speed in each leg and its variation coefficient were evaluated based on the official results of the competition and footage recorded during the race. The results showed that the total time and leg time for each leg were significantly shorter in Group A compared to those in Group B (p < 0.05). In both groups, the Lap 4 run was significantly slower than those of Laps 1-3 (p < 0.05), while there was no significant difference in the running speed to average speed ratio across all laps between the groups (p < 0.05). Thus, there was a difference in running speed between the groups, but no significant difference in pacing. The results of this study serve as basic data for examining superior pacing strategies, although further studies on a wide range of competition levels are necessary.

Exercise Intensity during Olympic-Distance Triathlon in Well-Trained Age-Group Athletes: An Observational Study.

The aim of this study was to examine the exercise intensity during the swimming, cycling, and running legs of nondraft legal, Olympic-distance triathlons in well-trained, age-group triathletes. Seventeen male triathletes completed incremental swimming, cycling, and running tests to exhaustion. Heart rate (HR) and workload corresponding to aerobic and anaerobic thresholds, maximal workloads, and maximal HR (HRmax) in each exercise mode were analyzed. HR and workload were monitored throughout the race. The intensity distributions in three HR zones for each discipline and five workload zones in cycling and running were quantified. The subjects were then assigned to a fast or slow group based on the total race time (range, 2 h 07 min-2 h 41 min). The mean percentages of HRmax in the swimming, cycling, and running legs were 89.8% ± 3.7%, 91.1% ± 4.4%, and 90.7% ± 5.1%, respectively, for all participants. The mean percentage of HRmax and intensity distributions during the swimming and cycling legs were similar between groups. In the running leg, the faster group spent relatively more time above HR at anaerobic threshold (AnT) and between workload at AnT and maximal workload. In conclusion, well-trained male triathletes performed at very high intensity throughout a nondraft legal, Olympic-distance triathlon race, and sustaining higher intensity during running might play a role in the success of these athletes.

Physicochemical properties of anodized-hydrothermally treated titanium with a nanotopographic surface structure promote osteogenic differentiation in dental pulp stem cells.

Purpose Implants made of anodized-hydrothermally treated commercially pure titanium with a nanotopographic surface structure (SA-treated c.p.Ti) may advantageously promote contact osteogenesis during the early stages of healing. We hypothesized that utilizing SA-treated c.p.Ti with dental pulp stem cells (DPSCs) might improve osteoconduction during the process of osseointegration. This in vitro study investigated the effect of initial adhesion of DPSCs to SA-treated c.p.Ti compared with conventional c.p.Ti and anodic oxide (AO) c.p.Ti.Methods DPSCs were obtained from the mandibular incisors of Sprague-Dawley rats and cultured without osteogenic induction medium on c.p.Ti, AO c.p.Ti, and SA-treated c.p.Ti disks for up to 14 days. The morphology, proliferation, and differentiation of DPSCs were assessed by scanning electron microscopy, an MTT assay, and Alizarin Red S staining, respectively. A real-time quantitative polymerase chain reaction was used to quantify the mRNA expression of osteocalcin, osteopontin, and bone sialoprotein.Results On all disks, the DPSCs appeared flattened with the formation of extensions over time. The filopodium-like extensions were closely bound to the SA-treated c.p.Ti surface. The proliferation of DPSCs was not significantly different among the c.p.Ti treatments. However, DPSCs on SA-treated c.p.Ti showed the greatest mRNA levels of osteopontin, osteocalcin, and bone sialoprotein, as well as increased Alizarin Red S staining.Conclusions The results of the present in vitro study demonstrate that the surface properties of SA-treated c.p.Ti disks enhance osteogenic differentiation of DPSCs and may facilitate mineralized matrix formation on SA-treated c.p.Ti implant surfaces, which can enhance early bone regeneration.

Efficacy of extracellular vesicles from dental pulp stem cells for bone regeneration in rat calvarial bone defects.

BACKGROUND: Extracellular vesicles (EVs) are known to be secreted by various cells. In particular, mesenchymal stem cell (MSC)-derived EVs (MSC-EVs) have tissue repair capacity and anti-inflammatory properties. Dental pulp stem cells (DPSCs), which are MSCs isolated from pulp tissue, are less invasive to the body than other MSCs and can be collected from young individuals. In this study, we investigated the efficacy of EVs secreted by DPSCs (DPSC-EVs) for bone formation. METHODS: DPSC-EVs were isolated from the cell culture medium of DPSCs. DPSC-EVs were unilaterally injected along with collagen (COL), beta-tricalcium phosphate (ß-TCP) or hydroxyapatite (HA) into rat calvarial bone defects. The effects of DPSC-EVs were analyzed by micro-computed tomography (micro-CT) and histological observation. RESULTS: Micro-CT showed that administration of DPSC-EVs with the abovementioned scaffolds resulted in bone formation in the periphery of the defects. DPSC-EVs/COL specifically resulted in bone formation in the center of the defects. Histological observation revealed that DPSC-EVs/COL promoted new bone formation. Administration of DPSC-EVs/COL had almost the same effect on the bone defect site as transplantation of DPSCs/COL. CONCLUSIONS: These results suggest that DPSC-EVs may be effective tools for bone tissue regeneration.

Exercise improves the quality of slow-wave sleep by increasing slow-wave stability.

Exercise can improve sleep by reducing sleep latency and increasing slow-wave sleep (SWS). Some studies, however, report adverse effects of exercise on sleep architecture, possibly due to a wide variety of experimental conditions used. We examined the effect of exercise on quality of sleep using standardized exercise parameters and novel analytical methods. In a cross-over intervention study we examined the effect of 60 min of vigorous exercise at 60% [Formula: see text]max on the metabolic state, assessed by core body temperature and indirect calorimetry, and on sleep quality during subsequent sleep, assessed by self-reported quality of sleep and polysomnography. In a novel approach, envelope analysis was performed to assess SWS stability. Exercise increased energy expenditure throughout the following sleep phase. The subjective assessment of sleep quality was not improved by exercise. Polysomnography revealed a shorter rapid eye movement latency and reduced time spent in SWS. Detailed analysis of the sleep electro-encephalogram showed significantly increased delta power in SWS (N3) together with increased SWS stability in early sleep phases, based on delta wave envelope analysis. Although vigorous exercise does not lead to a subjective improvement in sleep quality, sleep function is improved on the basis of its effect on objective EEG parameters.

LDH isoenzyme 5 is an index of early onset muscle soreness during prolonged running.

BACKGROUND: Muscle soreness is also induced during prolonged running such as a full marathon, and muscle soreness and increased damage markers are detected immediately after such a running. We named this muscle soreness, early onset muscle soreness (EOMS). Additionally, lactate dehydrogenase (LDH) level which has some isoenzyme is increased immediately after prolonged exercise. However, it is unclear that EOMS is related to muscle damage markers on prolonged running. This study aimed to determine at which point EOMS, and muscle damage markers are related to EOMS during prolonged running. METHODS: We studied 11 male subjects who habitually perform aerobic exercise. They ran 30 km at 90% of ventilatory threshold intensity. Every 10 km, we estimated perceived muscle soreness, and sampled blood to measure muscle and liver damage, inflammation, and oxidative stress (d-ROM and BAP) markers. RESULTS: Muscle soreness score lower limbs were significantly appeared at 20 km compared to that at 0 km. Serum lactate dehydrogenase (LDH) level increased at 30 km compared to that at 0 km. LDH isoenzymes 3, 4, and 5, and neutrophils significantly increased at 30 km compared to those at 0 km. Serum LDH isoenzyme 5 and change in aspartate aminotransferase significantly increased at 20 km. In addition, there was a significant correlation between the thigh NRS and amount of serum LDH isoenzyme 5 from 0 km to 20 km. d-ROM and BAP increased at 10 km compared to those at 0 km. CONCLUSIONS: EOMS started to occur at 20 km during a 30 km running task. Our data suggest that LDH isoenzyme 5 is a marker of occurrence in EOMS during prolonged running.

Discovery of 4-Piperazine Isoquinoline Derivatives as Potent and Brain-Permeable Tau Prion Inhibitors with CDK8 Activity.

Tau prions feature in the brains of patients suffering from Alzheimer's disease and other tauopathies. For the development of therapeutics that target the replication of tau prions, a high-content, fluorescence-based cell assay was developed. Using this high-content phenotypic screen for nascent tau prion formation, a 4-piperazine isoquinoline compound (1) was identified as a hit with an EC50 value of 390 nM and 0.04 K p,uu. Analogs were synthesized using a hypothesis-based approach to improve potency and in vivo brain penetration resulting in compound 25 (EC50 = 15 nM; K p,uu = 0.63). We investigated the mechanism of action of this series and found that a small set of active compounds were also CDK8 inhibitors.

Neuromuscular stimulation ameliorates ischemia-induced walking impairment in the rat claudication model.

Intermittent claudication (IC) is the most common symptom of peripheral arterial disease which significantly deteriorates the quality of life of patients. Exercise training is by far the most effective treatment for IC; however, the underlying mechanisms remain elusive. To determine the local mechanisms by which exercise training improves walking performance in claudicants, we developed an implantable device to locally induce ischemic skeletal muscle contraction mimicking exercise via electrical stimulation (ES). Rats were assigned to four groups, Sham, Ischemia (Isch), Isch + exercise and Isch + ES groups. Following both unilateral femoral and iliac artery occlusion, rats showed sustained impairment of walking performance in the treadmill test. Chronic low-frequency ES of ischemic skeletal muscles for 2 weeks significantly recovered the occlusion-induced walking impairment in the rat claudication model. We further analyzed the ischemic skeletal muscles immunohistochemically following ES or exercise training; both ES and exercise training significantly increased capillaries in the ischemic skeletal muscles and shifted the muscle fibers toward oxidative types. These findings demonstrate that ES takes on common features of exercise in the rat claudication model, which may facilitate investigations on the local mechanisms of exercise-induced functional recovery.

Aß and tau prion-like activities decline with longevity in the Alzheimer's disease human brain.

The hallmarks of Alzheimer's disease (AD) are the accumulation of Aß plaques and neurofibrillary tangles composed of hyperphosphorylated tau. We developed sensitive cellular assays using human embryonic kidney-293T cells to quantify intracellular self-propagating conformers of Aß in brain samples from patients with AD or other neurodegenerative diseases. Postmortem brain tissue from patients with AD had measurable amounts of pathological Aß conformers. Individuals over 80 years of age had the lowest amounts of prion-like Aß and phosphorylated tau. Unexpectedly, the longevity-dependent decrease in self-propagating tau conformers occurred in spite of increasing amounts of total insoluble tau. When corrected for the abundance of insoluble tau, the ability of postmortem AD brain homogenates to induce misfolded tau in the cellular assays showed an exponential decrease with longevity, with a half-life of about one decade over the age range of 37 to 99 years. Thus, our findings demonstrate an inverse correlation between longevity in patients with AD and the abundance of pathological tau conformers. Our cellular assays can be applied to patient selection for clinical studies and the development of new drugs and diagnostics for AD.

Relationship between oxygen cost and C-reactive protein response to marathon running in college recreational runners.

PURPOSE: Individual variations in response of C-reactive protein (CRP) to acute strenuous exercise are less well known. The purpose of this study was to investigate the relationship between running economy and systemic inflammation following a marathon. MATERIALS AND METHODS: Sixteen college recreational runners participated in this study. To measure maximal oxygen uptake and running economy, the treadmill running test was performed 1-2 weeks before the marathon race. Running economy was defined as oxygen cost (mL/kg/km) at submaximal running. CRP and muscle damage markers (creatine kinase and lactate dehydrogenase) were measured before and 1, 2, and 3 days after the race. RESULTS: All subjects completed the race in 4 hours 7 minutes 43 seconds±44 minute 29 seconds [mean±SD]. The marathon running significantly increased CRP and muscle damage markers. The levels of inflammation and muscle damage peaked after 1 day and remained high throughout the 3-day recovery period compared to that before the race. Spearman correlation analysis showed that the change in CRP level was significantly positively correlated with oxygen cost (r=0.619, P=0.011) but not maximal oxygen uptake. There was no significant relationship in responses between muscle damage markers and CRP. CONCLUSION: These findings suggest that running economy is related to postmarathon race CRP response. Further study to clarify the cause of the relationship and clinical significance of transient increase in CRP is necessary.

α-Synuclein: Multiple System Atrophy Prions.

Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease arising from the misfolding and accumulation of the protein α-synuclein in oligodendrocytes, where it forms glial cytoplasmic inclusions (GCIs). Several years of studying synthetic α-synuclein fibrils has provided critical insight into the ability of α-synuclein to template endogenous protein misfolding, giving rise to fibrillar structures capable of propagating from cell to cell. However, more recent studies with MSA-derived α-synuclein aggregates have shown that they have a similar ability to undergo template-directed propagation, like PrP prions. Almost 20 years after α-synuclein was discovered as the primary component of GCIs, α-synuclein aggregates isolated from MSA patient samples were shown to infect cultured mammalian cells and also to transmit neurological disease to transgenic mice. These findings argue that α-synuclein becomes a prion in MSA patients. In this review, we discuss the in vitro and in vivo data supporting the recent classification of MSA as a prion disease.

Effects of Marathon Running on Aerobic Fitness and Performance in Recreational Runners One Week after a Race.

It is not clear whether or not recreational runners can recover aerobic fitness and performance within one week after marathon running. This study aimed to investigate the effects of running a marathon race on aerobic fitness and performance one week later. Eleven recreational runners (six men, five women) completed the race in 3 h 36 min 20 s ± 41 min 34 s (mean ± standard deviation). Before and 7 days after the race, they performed a treadmill running test. Perceived muscle soreness was assessed before the race and for the following 7 days. The magnitude of changes in the treadmill running test was considered possibly trivial for maximal oxygen uptake ([Formula: see text]O2max) (mean difference -1.2 ml/kg/min; ±90% confidence limits 2 ml/kg/min), unclear for %[Formula: see text]O2max at anaerobic threshold (AT) (-0.5; ±4.1%) and RE (0.2; ±3.5 ml/kg/km), and likely trivial for both velocity at AT and peak (-0.2; ±0.49 km/h and -0.3; ±0.28 km/h). Perceived muscle soreness increased until 3 days after the race, but there were no clear differences between the values before the race and 4-7 days after it. These results show that physiological capacity associated with marathon running performance is recovered within 7 days after a marathon run.