Physical exercise has emerged as an alternative treatment for patients with depressive disorder. Recent animal studies show that exercise protects from depression by increased skeletal muscle kynurenine aminotransferase (KAT) expression which shifts the kynurenine metabolism away from the neurotoxic kynurenine (KYN) to the production of kynurenic acid (KYNA). In the present study, we investigated the effect of exercise on kynurenine metabolism in humans. KAT gene and protein expression was increased in the muscles of endurance-trained subjects compared with untrained subjects. Endurance exercise caused an increase in plasma KYNA within the first hour after exercise. In contrast, a bout of high-intensity eccentric exercise did not lead to increased plasma KYNA concentration. Our results show that regular endurance exercise causes adaptations in kynurenine metabolism which can have implications for exercise recommendations for patients with depressive disorder.

Acclimatization to hypoxia leads to a reduction in plasma volume (PV) that restores arterial O 2 content. r Findings from studies investigating the mechanisms underlying this PV contraction have been controversial, possibly as experimental conditions were inadequately controlled. r We examined the mechanisms underlying the PV contraction evoked by 4 days of exposure to hypobaric hypoxia (HH) in 11 healthy lowlanders, while strictly controlling water intake, diet, temperature and physical activity. r Exposure to HH-induced an ∼10% PV contraction that was accompanied by a reduction in total circulating protein mass, whereas diuretic fluid loss and total body water remained unchanged. r Our data support an oncotically driven fluid redistribution from the intra-to the extravascular space, rather than fluid loss, as the mechanism underlying HH-induced PV contraction.

No abstract

Key points How defects in muscle contractile function contribute to weakness in amyotrophic lateral sclerosis (ALS) were systematically investigated. Weakness in whole muscles from late stage SOD1G93A mice was explained by muscle atrophy as seen by reduced mass and maximal force. On the other hand, surviving single muscle fibres in late stage SOD1G93A have preserved intracellular Ca2+ handling, normal force‐generating capacity and increased fatigue resistance. These intriguing findings provide a substrate for therapeutic interventions to potentiate muscular capacity and delay the progression of the ALS phenotype. Abstract Amyotrophic lateral sclerosis (ALS) is a motor neuron disease characterized by degeneration and loss of motor neurons, leading to severe muscle weakness and paralysis. The SOD1G93A mouse model of ALS displays motor neuron degeneration and a phenotype consistent with human ALS. The purpose of this study was to determine whether muscle weakness in ALS can be attributed to impaired intrinsic force generation in skeletal muscles. In the current study, motor neuron loss and decreased force were evident in whole flexor digitorum brevis (FDB) muscles of mice in the late stage of disease (125–150 days of age). However, in intact single muscle fibres, specific force, tetanic myoplasmic free [Ca2+] ([Ca2+]i), and resting [Ca2+]i remained unchanged with disease. Fibre‐type distribution was maintained in late‐stage SOD1G93A FDB muscles, but remaining muscle fibres displayed greater fatigue resistance compared to control and showed increased expression of myoglobin and mitochondrial respiratory chain proteins that are important determinants of fatigue resistance. Expression of genes central to both mitochondrial biogenesis and muscle atrophy where increased, suggesting that atrophic and compensatory adaptive signalling occurs simultaneously within the muscle tissue. These results support the hypothesis that muscle weakness in SOD1G93A is primarily attributed to neuromuscular degeneration and not intrinsic muscle fibre defects. In fact, surviving muscle fibres displayed maintained adaptive capacity with an exercise training‐like phenotype, which suggests that compensatory mechanisms are activated that can function to delay disease progression.

There is a risk of hip injury in dives to the side by soccer goalkeepers. In this study, we assessed hip loading in goalkeepers when performing such dives. The experiments were conducted in a laboratory setting using an in-ground force plate as well as on a grass surface when the athletes were equipped with force sensors. The forces acting on the hip were measured and high-speed video analysis was performed, allowing the investigation of the dive characteristics and techniques. The peak force values recorded in the laboratory setting ranged from 3 to 8 kN, which corresponded to 4.2-8.6 times body weight. The vertical impact velocities reached 3.25 m . s(-1). In the field experiments, a hip loading of 87-183 N . cm(-2) was determined. We found that goalkeepers who perform a rolling motion reduce their hip loading. The data provided by this study add to the biomechanics database and contribute to the establishment of injury criteria. Such information is necessary to develop and implement strategies to help prevent hip injuries.

The protein a-actinin-3 expressed in fast-twitch skeletal muscle fiber is absent in 1.5 billion people worldwide due to homozygosity for a nonsense polymorphism in ACTN3 (R577X). The prevalence of the 577X allele increased as modern humans moved to colder climates, suggesting a link between a-actinin-3 deficiency and improved cold tolerance. Here, we show that humans lacking a-actinin-3 (XX) are superior in maintaining core body temperature during cold-water immersion due to changes in skeletal muscle thermogenesis. Muscles of XX individuals displayed a shift toward more slow-twitch isoforms of myosin heavy chain (MyHC) and sarcoplasmic reticulum (SR) proteins, accompanied by altered neuronal muscle activation resulting in increased tone rather than overt shivering. Experiments on Actn3 knockout mice showed no alterations in brown adipose tissue (BAT) properties that could explain the improved cold tolerance in XX individuals. Thus, this study provides a mechanism for the positive selection of the ACTN3 X-allele in cold climates and supports a key thermogenic role of skeletal muscle during cold exposure in humans.

High altitude exposure typically reduces endothelial function, and this is modulated by hemoconcentration resulting from plasma volume contraction. However, the specific impact of hypobaric hypoxia, independent of external factors (e.g. cold, varying altitudes, exercise, diet, dehydration) on endothelial function is unknown. We examined the temporal changes in blood viscosity, shear stress and endothelial function and the impact of plasma volume expansion (PVX) during exposure to hypobaric hypoxia while controlling for external factors. Eleven healthy males (25±4 years; mean±SD) completed two four-day chamber visits (normoxia [NX] and hypobaric hypoxia [HH; equivalent altitude: 3500m]) in a cross-over design. Endothelial function was assessed via flow-mediated dilation in response to transient (reactive hyperemia; RH-FMD) and sustained (progressive handgrip exercise; SS-FMD) increases in shear stress prior to entering and after 1h, 6h, 12h, 48h and 96h in the chamber. During HH, endothelial function was also measured on the last day after PVX to pre-exposure levels (1140±320 ml balanced crystalloid solution). Blood viscosity and arterial shear stress increased on the first day during HH compared to NX and remained elevated at 48h and 96h (P<0.005). RH-FMD did not differ during HH compared to NX and was unaffected by PVX despite reductions in blood viscosity (P<0.05). The stimulus-response slope of increases in shear stress to vasodilation during SS-FMD was preserved in HH and increased by 44±73% following PVX (P=0.023). These findings suggest that endothelial function is maintained in HH when other stressors are absent and that PVX improves endothelial function in a shear stress stimulus-specific manner.

We investigated whether low arterial oxygen tension (PaO2) or hypoxia-induced plasma volume (PV) contraction, which reduces central blood volume (BV) and atrial distension, explain reduction in circulating atrial natriuretic peptide (ANP) after prolonged hypoxic exposure. Ten healthy males were exposed for four days to hypobaric hypoxia corresponding to an altitude of 3,500m. PV changes were determined by carbon monoxide rebreathing. Venous plasma concentrations of mid-regional proANP (MR-ProANP) were measured before and at the end of the exposure. At the latter time-point the measurement was repeated after i. restoration of PaO2 by breathing a hyperoxic gas mixture for 30min and ii. restoration of BV by fluid infusion. Correspondingly, left ventricular end-diastolic volume (LVEDV), left atrial area (LAA) and right atrial area (RAA) were determined by ultrasound before exposure, and both pre and post fluid infusion at the end of the exposure. Hypoxic exposure reduced MR-ProANP from 37.9±18.5 to 24.5±10.3 pmol/l (p=0.034), LVEDV from 107.4±33.5 to 91.6±26.3 ml (p=0.005), LAA from 15.8±4.9 to 13.3±4.2 cm² (p=0.007) and RAA from 16.2±3.1 to 14.3±3.5 cm² (p=0.001). Hyperoxic breathing did not affect MR-ProANP (24.8±12.3 pmol/l, p=0.890). Conversely, fluid infusion restored LVEDV, LAA and RAA to near baseline values (108.0±29.3 ml, 17.2±5.7 cm² and 17.2±3.1 cm², p>0.05 vs. baseline) and increased MR-ProANP to 29.5±13.3 pmol/l (p=0.010 vs. pre-infusion and p=0.182 vs. baseline). These findings support that ANP reduction in hypoxia is at least partially attributed to plasma volume contraction, whereas reduced PaO2 does not seem to contribute.