Minute-scale oscillatory sequences in medial entorhinal cortex.

The medial entorhinal cortex (MEC) hosts many of the brain's circuit elements for spatial navigation and episodic memory, operations that require neural activity to be organized across long durations of experience1. Whereas location is known to be encoded by spatially tuned cell types in this brain region2,3, little is known about how the activity of entorhinal cells is tied together over time at behaviourally relevant time scales, in the second-to-minute regime. Here we show that MEC neuronal activity has the capacity to be organized into ultraslow oscillations, with periods ranging from tens of seconds to minutes. During these oscillations, the activity is further organized into periodic sequences. Oscillatory sequences manifested while mice ran at free pace on a rotating wheel in darkness, with no change in location or running direction and no scheduled rewards. The sequences involved nearly the entire cell population, and transcended epochs of immobility. Similar sequences were not observed in neighbouring parasubiculum or in visual cortex. Ultraslow oscillatory sequences in MEC may have the potential to couple neurons and circuits across extended time scales and serve as a template for new sequence formation during navigation and episodic memory formation.

A microbiome-dependent gut-brain pathway regulates motivation for exercise.

Exercise exerts a wide range of beneficial effects for healthy physiology1. However, the mechanisms regulating an individual's motivation to engage in physical activity remain incompletely understood. An important factor stimulating the engagement in both competitive and recreational exercise is the motivating pleasure derived from prolonged physical activity, which is triggered by exercise-induced neurochemical changes in the brain. Here, we report on the discovery of a gut-brain connection in mice that enhances exercise performance by augmenting dopamine signalling during physical activity. We find that microbiome-dependent production of endocannabinoid metabolites in the gut stimulates the activity of TRPV1-expressing sensory neurons and thereby elevates dopamine levels in the ventral striatum during exercise. Stimulation of this pathway improves running performance, whereas microbiome depletion, peripheral endocannabinoid receptor inhibition, ablation of spinal afferent neurons or dopamine blockade abrogate exercise capacity. These findings indicate that the rewarding properties of exercise are influenced by gut-derived interoceptive circuits and provide a microbiome-dependent explanation for interindividual variability in exercise performance. Our study also suggests that interoceptomimetic molecules that stimulate the transmission of gut-derived signals to the brain may enhance the motivation for exercise.

Theropod trackways as indirect evidence of pre-avian aerial behavior.

Body fossils set limits on feasible reconstructions of functional capacity and behavior in theropod dinosaurs, but do not document in-life behaviors. In contrast, trace fossils such as footprints preserve in-life behaviors that can potentially test and enhance existing reconstructions. Here, we demonstrate how theropod trackways can be used as indirect evidence of pre-avian aerial behavior, expanding the approaches available to study vertebrate flight origins. This involved exploring the behavioral implications of a two-toed Cretaceous-aged theropod trackway produced by a small, bird-like microraptorine moving at high speed. Applying first principle running biomechanics, we were able to conclude that the trackway is atypical, indirectly evidencing pre-avian aerial behavior. This trackway documents the evidence of wing-assisted aerodynamic force production during locomotion, supporting a broader distribution of this behavior than currently known. These findings support previously proposed aerial behavior in early bird-like theropods, showing how trackways will help to deepen our understanding of theropod flight origins.

Running exercise alleviates hippocampal neuroinflammation and shifts the balance of microglial M1/M2 polarization through adiponectin/AdipoR1 pathway activation in mice exposed to chronic unpredictable stress.

Running exercise has been shown to alleviate depressive symptoms. However, the mechanism underlying the antidepressant effects of running exercise is not fully understood. The imbalance of M1/M2 microglia phenotype/polarization and concomitant dysregulation of neuroinflammation play crucial roles in the pathogenesis of depression. Running exercise increases circulating levels of adiponectin which is known to cross the blood‒brain barrier and suppress inflammatory responses. AdipoR1 is an adiponectin receptor that is involved in regulating microglial phenotypes and activation states. However, whether running exercise regulates hippocampal microglial phenotypes and neuroinflammation through adiponectin/AdipoR1 to exert its antidepressant effects remains unclear. In the current study, 4 weeks of running exercise significantly alleviated the depressive-like behaviors of chronic unpredictable stress (CUS)-exposed mice. Moreover, running exercise decreased the microglial numbers and altered microglial morphology in three subregions of the hippocampus to restore the M1/M2 balance; these effects were accompanied by regulation of pro-/anti-inflammatory cytokine production and secretion in CUS-exposed mice. These effects may involve elevation of peripheral tissue (adipose tissue and muscle) and plasma adiponectin levels, and hippocampal AdipoR1 levels as well as activation of the AMPK-NF-κB/STAT3 signaling pathway by running exercise. When an adeno-associated virus was used to knock down hippocampal AdipoR1, mice showed depressive-like behaviors and alterations in microglia and inflammatory factor expression in the hippocampus that were similar to those observed in CUS-exposed mice. Together, these results suggest that running exercise maintains the M1/M2 balance and inhibits neuroinflammation in the hippocampus of CUS-exposed mice. These effects might occur via adiponectin/AdipoR1-mediated activation of the AMPK-NF-κB/STAT3 signaling pathway.

A simulation framework to determine optimal strength training and musculoskeletal geometry for sprinting and distance running.

Musculoskeletal geometry and muscle volumes vary widely in the population and are intricately linked to the performance of tasks ranging from walking and running to jumping and sprinting. As an alternative to experimental approaches, where it is difficult to isolate factors and establish causal relationships, simulations can be used to independently vary musculoskeletal geometry and muscle volumes, and develop a fundamental understanding. However, our ability to understand how these parameters affect task performance has been limited due to the high computational cost of modelling the necessary complexity of the musculoskeletal system and solving the requisite multi-dimensional optimization problem. For example, sprinting and running are fundamental to many forms of sport, but past research on the relationships between musculoskeletal geometry, muscle volumes, and running performance has been limited to observational studies, which have not established cause-effect relationships, and simulation studies with simplified representations of musculoskeletal geometry. In this study, we developed a novel musculoskeletal simulator that is differentiable with respect to musculoskeletal geometry and muscle volumes. This simulator enabled us to find the optimal body segment dimensions and optimal distribution of added muscle volume for sprinting and marathon running. Our simulation results replicate experimental observations, such as increased muscle mass in sprinters, as well as a mass in the lower end of the healthy BMI range and a higher leg-length-to-height ratio in marathon runners. The simulations also reveal new relationships, for example showing that hip musculature is vital to both sprinting and marathon running. We found hip flexor and extensor moment arms were maximized to optimize sprint and marathon running performance, and hip muscles the main target when we simulated strength training for sprinters. Our simulation results provide insight to inspire future studies to examine optimal strength training. Our simulator can be extended to other athletic tasks, such as jumping, or to non-athletic applications, such as designing interventions to improve mobility in older adults or individuals with movement disorders.

Muscle fibre typology affects whole-body metabolic rate during isolated muscle contractions and human locomotion.

The wide variation in muscle fibre type distribution across individuals, along with the very different energy consumption rates in slow versus fast muscle fibres, suggests that muscle fibre typology contributes to inter-individual differences in metabolic rate during exercise. However, this has been hard to demonstrate due to the gap between a single muscle fibre and full-body exercises. We investigated the isolated effect of triceps surae muscle contraction velocity on whole-body metabolic rate during cyclic contractions in individuals a priori selected for their predominantly slow (n = 11) or fast (n = 10) muscle fibre typology by means of proton magnetic resonance spectroscopy (1H-MRS). Subsequently, we examined their whole-body metabolic rate during walking and running at 2 m/s, exercises with comparable metabolic rates but distinct triceps surae muscle force and velocity demands (walking: low force, high velocity; running: high force, low velocity). Increasing triceps surae contraction velocity during cyclic contractions elevated net whole-body metabolic rate for both typology groups. However, the slow group consumed substantially less net metabolic energy at the slowest contraction velocity, but the metabolic difference between groups diminished at faster velocities. Consistent with the more economic force production during slow contractions, the slow group exhibited lower metabolic rates than the fast group while running, whereas metabolic rates were similar during walking. These findings provide important insights into the influence of muscle fibre typology on whole-body metabolic rate and emphasize the importance of considering muscle mechanical demands to understand muscle fibre typology related differences in whole-body metabolic rates. KEY POINTS: Muscle fibre typology is often suggested to affect whole-body metabolic rate, yet convincing in vivo evidence is lacking. Using isolated plantar flexor muscle contractions in individuals a priori selected for their predominantly slow or fast muscle fibre typology, we demonstrated that having predominantly slow muscle fibres provides a metabolic advantage during slow muscle contractions, but this benefit disappeared at faster contractions. We extended these results to full-body exercises, where we demonstrated that higher proportions of slow fibres associated with better economy during running but not when walking. These findings provide important insights into the influence of muscle fibre typology on whole-body metabolic rate and emphasize the importance of considering muscle mechanical demands to understand muscle fibre typology related differences in whole-body metabolic rate.

Myoglobin deficiency impairs maximal oxygen uptake and exercise performance: a lesson from Mb-/- mice.

Myoglobin (Mb) plays an important role at rest and during exercise as a reservoir of oxygen and has been suggested to regulate NO• bioavailability under hypoxic/acidic conditions. However, its ultimate role during exercise is still a subject of debate. We aimed to study the effect of Mb deficiency on maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and exercise performance in myoglobin knockout mice (Mb-/- ) when compared to control mice (Mb+/+ ). Furthermore, we also studied NO• bioavailability, assessed as nitrite (NO2 - ) and nitrate (NO3 - ) in the heart, locomotory muscle and in plasma, at rest and during exercise at exhaustion both in Mb-/- and in Mb+/+ mice. The mice performed maximal running incremental exercise on a treadmill with whole-body gas exchange measurements. The Mb-/- mice had lower body mass, heart and hind limb muscle mass (P < 0.001). Mb-/- mice had significantly reduced maximal running performance (P < 0.001). V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ expressed in ml min-1 in Mb-/ - mice was 37% lower than in Mb+/+ mice (P < 0.001) and 13% lower when expressed in ml min-1  kg body mass-1 (P = 0.001). Additionally, Mb-/- mice had significantly lower plasma, heart and locomotory muscle NO2 - levels at rest. During exercise NO2 - increased significantly in the heart and locomotory muscles of Mb-/- and Mb+/+ mice, whereas no significant changes in NO2 - were found in plasma. Our study showed that, contrary to recent suggestions, Mb deficiency significantly impairs V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance in mice. KEY POINTS: Myoglobin knockout mice (Mb-/- ) possess lower maximal oxygen uptake ( V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ ) and poorer maximal running performance than control mice (Mb+/+ ). Respiratory exchange ratio values at high running velocities in Mb-/- mice are higher than in control mice suggesting a shift in substrate utilization towards glucose metabolism in Mb-/- mice at the same running velocities. Lack of myoglobin lowers basal systemic and muscle NO• bioavailability, but does not affect exercise-induced NO2 - changes in plasma, heart and locomotory muscles. The present study demonstrates that myoglobin is of vital importance for V ̇ O 2 max ${\dot V_{{{\mathrm{O}}_2}\max }}$ and maximal running performance as well as explains why previous studies have failed to prove such a role of myoglobin when using the Mb-/- mouse model.

Treadmill running and mechanical overloading improved the strength of the plantaris muscle in the dystrophin-desmin double knockout (DKO) mouse.

Limited knowledge exists regarding the chronic effect of muscular exercise on muscle function in a murine model of severe Duchenne muscular dystrophy (DMD). Here we determined the effects of 1 month of voluntary wheel running (WR), 1 month of enforced treadmill running (TR) and 1 month of mechanical overloading resulting from the removal of the synergic muscles (OVL) in mice lacking both dystrophin and desmin (DKO). Additionally, we examined the effect of activin receptor administration (AR). DKO mice, displaying severe muscle weakness, atrophy and greater susceptibility to contraction-induced functional loss, were exercised or treated with AR at 1 month of age and in situ force production of lower leg muscle was measured at the age of 2 months. We found that TR and OVL increased absolute maximal force and the rate of force development of the plantaris muscle in DKO mice. In contrast, those of the tibialis anterior (TA) muscle remained unaffected by TR and WR. Furthermore, the effects of TR and OVL on plantaris muscle function in DKO mice closely resembled those in mdx mice, a less severe murine DMD model. AR also improved absolute maximal force and the rate of force development of the TA muscle in DKO mice. In conclusion, exercise training improved plantaris muscle weakness in severely affected dystrophic mice. Consequently, these preclinical results may contribute to fostering further investigations aimed at assessing the potential benefits of exercise for DMD patients, particularly resistance training involving a low number of intense muscle contractions. KEY POINTS: Very little is known about the effects of exercise training in a murine model of severe Duchenne muscular dystrophy (DMD). One reason is that it is feared that chronic muscular exercise, particularly that involving intense muscle contractions, could exacerbate the disease. In DKO mice lacking both dystrophin and desmin, characterized by severe lower leg muscle weakness, atrophy and fragility in comparison to the less severe DMD mdx model, we found that enforced treadmill running improved absolute maximal force of the plantaris muscle, while that of tibialis anterior muscle remained unaffected by both enforced treadmill and voluntary wheel running. Furthermore, mechanical overloading, a non-physiological model of chronic resistance exercise, reversed plantaris muscle weakness. Consequently, our findings may have the potential to alleviate concerns and pave the way for exploring the prescription of endurance and resistance training as a viable therapeutic approach for the treatment of dystrophic patients. Additionally, such interventions may serve in mitigating the pathophysiological mechanisms induced by physical inactivity.

Brain mechanisms discriminating enactive mental simulations of running and plogging.

Enactive cognition emphasizes co-constructive roles of humans and their environment in shaping cognitive processes. It is specifically engaged in the mental simulation of behaviors, enhancing the connection between perception and action. Here we investigated the core network of brain regions involved in enactive cognition as applied to mental simulations of physical exercise. We used a neuroimaging paradigm in which participants (N = 103) were required to project themselves running or plogging (running while picking-up litter) along an image-guided naturalistic trail. Using both univariate and multivariate brain imaging analyses, we find that a broad spectrum of brain activation discriminates between the mental simulation of plogging versus running. Critically, we show that self-reported ratings of daily life running engagement and the quality of mental simulation (how well participants were able to imagine themselves running) modulate the brain reactivity to plogging versus running. Finally, we undertook functional connectivity analyses centered on the insular cortex, which is a key region in the dynamic interplay between neurocognitive processes. This analysis revealed increased positive and negative patterns of insular-centered functional connectivity in the plogging condition (as compared to the running condition), thereby confirming the key role of the insular cortex in action simulation involving complex sets of mental mechanisms. Taken together, the present findings provide new insights into the brain networks involved in the enactive mental simulation of physical exercise.

Effects of long-term voluntary wheel running and selective breeding for wheel running on femoral nutrient canals.

The nutrient artery provides ~50%-70% of the total blood volume to long bones in mammals. Studying the functional characteristics of this artery in vivo can be difficult and expensive, so most researchers have measured the nutrient foramen, an opening on the outer surface of the bone that served as the entry point for the nutrient artery during development and bone ossification. Others have measured the nutrient canal (i.e., the passage which the nutrient artery once occupied), given that the external dimensions of the foramen do not necessarily remain uniform from the periosteal surface to the medullary cavity. The nutrient canal, as an indicator of blood flow to long bones, has been proposed to provide a link to studying organismal activity (e.g., locomotor behavior) from skeletal morphology. However, although external loading from movement and activity causes skeletal remodeling, it is unclear whether it affects the size or configuration of nutrient canals. To investigate whether nutrient canals can exhibit phenotypic plasticity in response to physical activity, we studied a mouse model in which four replicate high runner (HR) lines have been selectively bred for high voluntary wheel-running behavior. The selection criterion is the average number of wheel revolutions on days 5 and 6 of a 6-day period of wheel access as young adults (~6-8 weeks old). An additional four lines are bred without selection to serve as controls (C). For this study, 100 female mice (half HR, half C) from generation 57 were split into an active group housed with wheels and a sedentary group housed without wheels for 12 weeks starting at ~24 days of age. Femurs were collected, soft tissues were removed, and femora were micro-computed tomography scanned at a resolution of 12 µm. We then imported these scans into AMIRA and created 3D models of femoral nutrient canals. We tested for evolved differences in various nutrient canal traits between HR and C mice, plastic changes resulting from chronic exercise, and the selection history-by-exercise interaction. We found few differences between the nutrient canals of HR versus C mice, or between the active and sedentary groups. We did find an interaction between selection history and voluntary exercise for the total number of nutrient canals per femur, in which wheel access increased the number of canals in C mice but decreased it in HR mice. Our results do not match those from an earlier study, conducted at generation 11, which was prior to the HR lines reaching selection limits for wheel running. The previous study found that mice from the HR lines had significantly larger total canal cross-sectional areas compared to those from C lines. However, this discrepancy is consistent with studies of other skeletal traits, which have found differences between HR and C mice to be somewhat inconsistent across generations, including the loss of some apparent adaptations with continued selective breeding after reaching a selection limit for wheel-running behavior.

Running, jumping, hunting, and scavenging: Functional analysis of vertebral mobility and backbone properties in carnivorans.

Carnivorans are well-known for their exceptional backbone mobility, which enables them to excel in fast running and long jumping, leading to them being among the most successful predators amongst terrestrial mammals. This study presents the first large-scale analysis of mobility throughout the presacral region of the vertebral column in carnivorans. The study covers representatives of 6 families, 24 genera and 34 species. We utilized a previously developed osteometry-based method to calculate available range of motion, quantifying all three directions of intervertebral mobility: sagittal bending (SB), lateral bending (LB), and axial rotation (AR). We observed a strong phylogenetic signal in the structural basis of the vertebral column (vertebral and joint formulae, length proportions of the backbone modules) and an insignificant phylogenetic signal in most characteristics of intervertebral mobility. This indicates that within the existing structure (stabilization of which occurred rather early in different phylogenetic lineages), intervertebral mobility in carnivorans is quite flexible. Our findings reveal that hyenas and canids, which use their jaws to seize prey, are characterized by a noticeably elongated cervical region and significantly higher SB and LB mobility of the cervical joints compared to other carnivorans. In representatives of other carnivoran families, the cervical region is very short, but the flexibility of the neck (both SB and LB) is significantly higher than that of short-necked odd-toed and even-toed ungulates. The lumbar region of the backbone in carnivorans is dorsomobile in the sagittal plane, being on average ~23° more mobile than in artiodactyls and ~38° more mobile than in perissodactyls. However, despite the general dorsomobility, only some representatives of Canidae, Felidae, and Viverridae are superior in lumbar flexibility to the most dorsomobile ungulates. The most dorsomobile artiodactyls are equal or even superior to carnivorans in their ability to engage in dorsal extension during galloping. In contrast, carnivorans are far superior to ungulates in their ability to engage ventral flexion. The cumulative SB in the lumbar region in carnivorans largely depends on the mode of running and hunting. Thus, adaptation to prolonged and enduring pursuit of prey in hyenas is accompanied by markedly reduced SB flexibility in the lumbar region. A more dorsostable run is also a characteristic of the Ursidae, and the peculiar maned wolf. Representatives of Felidae and Canidae have significantly more available SB mobility in the lumbar region. However, they fully engage it only occasionally at key moments of the hunt associated with the direct capture of the prey or when running in a straight line at maximum speed.

Influence of Menstrual Cycle and Oral Contraceptive Phases on Bone (re)modelling Markers in Response to Interval Running.

To explore how sex hormone fluctuations may affect bone metabolism, this study aimed to examine P1NP and ß-CTX-1 concentrations across the menstrual and oral contraceptive (OC) cycle phases in response to running. 17ß-oestradiol, progesterone, P1NP and ß-CTX-1 were analysed pre- and post-exercise in eight eumenorrheic females in the early-follicular, late-follicular, and mid-luteal phases, while 8 OC users were evaluated during the withdrawal and active pill-taking phases. The running protocol consisted of 8 × 3min treadmill runs at 85% of maximal aerobic speed. 17ß-oestradiol concentrations (pg·ml-1) were lower in early-follicular (47.22 ± 39.75) compared to late-follicular (304.95 ± 235.85;p = < 0.001) and mid-luteal phase (165.56 ± 80.6;p = 0.003) and higher in withdrawal (46.51 ± 44.09) compared to active pill-taking phase (10.88 ± 11.24;p < 0.001). Progesterone (ng·ml-1) was higher in mid-luteal (13.214 ± 4.926) compared to early-follicular (0.521 ± 0.365; p < 0.001) and late-follicular phase (1.677 ± 2.586;p < 0.001). In eumenorrheic females, P1NP concentrations (ng·ml-1) were higher in late-follicular (69.97 ± 17.84) compared to early-follicular (60.96 ± 16.64;p = 0.006;) and mid-luteal phase (59.122 ± 11.77;p = 0.002). ß-CTX-1 concentrations (ng·ml-1) were lower in mid-luteal (0.376 ± 0.098) compared to late-follicular (0.496 ± 0.166; p = 0.001) and early-follicular phase (0.452 ± 0.148; p = 0.039). OC users showed higher post-exercise P1NP concentrations in withdrawal phase (61.75 ± 8.32) compared to post-exercise in active pill-taking phase (45.45 ± 6;p < 0.001). Comparing hormonal profiles, post-exercise P1NP concentrations were higher in early-follicular (66.91 ± 16.26;p < 0.001), late-follicular (80.66 ± 16.35;p < 0.001) and mid-luteal phases (64.57 ± 9.68;p = 0.002) to active pill-taking phase. These findings underscore the importance of studying exercising females with different ovarian hormone profiles, as changes in sex hormone concentrations affect bone metabolism in response to running, showing a higher post-exercise P1NP concentrations in all menstrual cycle phases compared with active pill-taking phase of the OC cycle.

The effect of bi-iliac breadth on core body temperature.

Thermoregulation is argued to be an important factor influencing body breadth in hominins based on the relationship of surface area to body mass first proposed by Bergmann. Selection for a narrow thorax, and thus a narrow pelvis, increases body surface area relative to body mass, which could be beneficial in hot climates if it leads to a decrease in core body temperature. However, the relationship between pelvic breadth and thermoregulation in humans has not been established. Although previous work has shown that bi-iliac breadth is significantly positively associated with latitude in humans, we lack an understanding of whether this association is due to climate-related selection, neutral evolutionary processes, or other selective pressures. A missing piece of the puzzle is whether body breadth at the iliac blades is an important factor in thermoregulation. Here, we examine this in a mixed-sex sample of 28 adult runners who ran for one hour at 3.14 m s-1 in a variety of climatic conditions while their core body temperatures were measured using internal temperature sensors. The association of maximum core temperature with anthropometric and demographic variables such as age, sex, mass, body fat percentage, and bi-iliac breadth was analyzed using a linear mixed-effect model. Due to the small sample size, the model was also bootstrapped. We found that an increase in absolute bi-iliac breadth was significantly associated with an increase in maximum core temperature. Overall, this preliminary analysis suggests a link between variation in bi-iliac breadth and maximum core body temperature during running, but further investigation is needed.

Arterial function in response to a 50 km ultramarathon in recreational athletes.

This study was performed to determine whether prolonged endurance running results in acute endothelial dysfunction and wave-reflection, as endothelial dysfunction and arterial stiffness are cardiovascular risk factors. Vascular function (conduit artery/macrovascular and resistance artery/microvascular) was assessed in 11 experienced runners (8 males, 3 females) before, during and after a 50 km ultramarathon. Blood pressure (BP), heart rate (HR), wave reflection, augmentation index (AIx) and AIx corrected for HR (AIx75) were taken at all time points-Baseline (BL), following 10, 20, 30 and 40 km, 1 h post-completion (1HP) and 24 h post-completion (24HP). Flow-mediated dilatation (FMD) and inflammatory biomarkers were examined at BL, 1HP and 24HP. Reactive hyperaemia area under the curve (AUC) and shear rate AUC to peak dilatation were lower (∼75%) at 1HP compared with BL (P < 0.001 for both) and reactive hyperaemia was higher at 24HP (∼27%) compared with BL (P = 0.018). Compared to BL, both mean central systolic BP and mean central diastolic BP were 7% and 10% higher, respectively, following 10 km and 6% and 9% higher, respectively, following 20 km, and then decreased by 5% and 8%, respectively, at 24HP (P < 0.05 for all). AIx (%) decreased following 20 km and following 40 km compared with BL (P < 0.05 for both) but increased following 40 km when corrected for HR (AIx75) compared with BL (P = 0.02). Forward wave amplitude significantly increased at 10 km (15%) compared with BL (P = 0.049), whereas backward wave reflection and reflected magnitude were similar at all time points. FMD and baseline diameter remained similar. These data indicate preservation of macrovascular (endothelial) function, but not microvascular function resulting from the 50 km ultramarathon.

Wheel Running During Pregnancy Alleviates Anxiety-and Depression-Like Behaviors During the Postpartum Period in Mice: The Roles of NLRP3 Neuroinflammasome Activation, Prolactin, and the Prolactin Receptor in the Hippocampus.

Despite the increase in the prevalence of postpartum depression among maternal disorder, its treatment outcomes remain suboptimal. Studies have shown that exercise can reduce postpartum depressive episodes in the mother, but the effects of exercise during pregnancy on maternal behavior and the potential mechanisms involved remain poorly understood. From the second day of pregnancy to the day of birth, dams exercised for 1 h a day by running on a controlled wheel. The maternal behaviors of the dams were assessed on postpartum day 2 to postpartum day 8. Chronic restraint stress was applied from postpartum day 2 to day 12. Blood was collected on postpartum days 3 and 8, then subjected to ELISA to determine the serum concentration of prolactin. The weight of each dam and the food intake were recorded. Anxiety- and depression-like behavioral tests were conducted, and hippocampal neuroinflammation and prolactin receptor levels were measured. The dams exhibited elevated levels of anxiety and depression, decreased serum prolactin levels, decreased prolactin receptor expression, and activation of NLRP3-mediated neuroinflammation in the hippocampus following the induction of postpartum chronic restraint stress, which were reversed with controlled wheel running during pregnancy. Overall, the findings of this study revealed that the preventive effects of exercise during pregnancy on postpartum anxiety-and depression-like behaviors were accompanied by increased serum prolactin levels, hippocampal prolactin receptor expression and hippocampal NLRP3-mediated neuroinflammation.

Tibial strains are sensitive to speed perturbations, but not grade perturbations, during running.

A fatigue-failure process is hypothesized to govern the development of tibial stress fractures, where bone damage is highly dependent on the peak strain magnitude. To date, much of the work examining tibial strain during running has ignored uphill and downhill running despite the prevalence of this terrain. This study examined the sensitivity of tibial strain to changes in running grade and speed using a combined musculoskeletal-finite element modelling routine. Seventeen participants ran on a treadmill at ±10, ±5 and 0 deg; at each grade, participants ran at 3.33 m s-1 and at a grade-adjusted speed of 2.50 and 4.17 m s-1 for uphill and downhill grades, respectively. Force and motion data were recorded in each grade and speed combination. Muscle and joint contact forces were estimated using inverse-dynamics-based static optimization. These forces were applied to a participant-adjusted finite element model of the tibia. None of the strain variables (50th and 95th percentile strain and strained volume ≥4000 µÎµ) differed as a function of running grade; however, all strain variables were sensitive to running speed (F1≥9.59, P≤0.03). In particular, a 1 m s-1 increase in speed resulted in a 9% (∼260 µÎµ) and 155% (∼600 mm3) increase in peak strain and strained volume, respectively. Overall, these findings suggest that faster running speeds, but not changes in running grade, may be more deleterious to the tibia.

Thermo-physiological changes and reproductive investment in a liolaemid lizard at the extreme of the slow-fast continuum.

Gravid female lizards often experience reduced thermal preferences and impaired locomotor performance. These changes have been attributed to the physical burden of the clutch, but some authors have suggested that they may be due to physiological adjustments. We compared the thermal biology and locomotor performance of the lizard Liolaemus wiegmannii 1 week before and 1 week after oviposition. We found that gravid females had a thermal preference 1°C lower than that of non-gravid females. This was accompanied by a change in the thermal dependence of maximum running speed. The thermal optimum for locomotor performance was 2.6°C lower before oviposition than after. At relatively low temperatures (22 and 26°C), running speeds of females before oviposition were up to 31% higher than for females after oviposition. However, at temperatures above 26°C, females achieved similar maximum running speeds (∼1.5 m s-1) regardless of reproductive stage. The magnitude of the changes in thermal parameters and locomotor performance of L. wiegmannii females was independent of relative clutch mass (clutches weighed up to 89% of post-oviposition body mass). This suggests that the changes are not simply due to the clutch mass, but are also due to physiological adjustments. Liolaemus wiegmannii females simultaneously adjusted their own physiology in a short period in order to improve locomotor performance and allocated energy for embryonic development during late gravid stage. Our findings have implications for understanding the mechanisms underlying life histories of lizards on the fast extreme of the slow-fast continuum, where physiological exhaustion could play an important role.

Include the females: morphology-performance relationships vary between sexes in lizards.

An animal's morphology influences its ability to perform essential tasks, such as locomoting to obtain prey or escape predators. While morphology-performance relationships are well-studied in lizards, most conclusions have been based only on male study subjects, leaving unanswered questions about females. Sex-specific differences are important to understand because females carry the bulk of the physiological demands of reproduction. Consequently, their health and survival can determine the fate of the population as a whole. To address this knowledge gap, we sampled introduced populations of common wall lizards (Podarcis muralis) in Ohio, USA. We measured a complete suite of limb and body dimensions of both males and females, and we measured sprint speeds while following straight and curved paths on different substrates. Using a multivariate statistical approach, we identified that body dimensions relative to snout-to-vent length in males were much larger compared with females and that body dimensions of P. muralis have changed over time in both sexes. We found that sprint speed along curved paths increased with relative limb size in both males and females. When following straight paths, male speed similarly increased as body dimensions increased; conversely, female speed decreased as body dimensions increased. Female sprint speed was also found to have less variation than that of males and was less affected by changes in body size and hindfoot length compared with males. This study thus provides insights into how selective pressures might shape males and females differently and the functional implications of sexual dimorphism.

Linking in vivo muscle dynamics to force-length and force-velocity properties reveals that guinea fowl lateral gastrocnemius operates at shorter than optimal lengths.

The isometric force-length (F-L) and isotonic force-velocity (F-V) relationships characterize the contractile properties of skeletal muscle under controlled conditions, yet it remains unclear how these properties relate to in vivo muscle function. Here, we map the in situ F-L and F-V characteristics of guinea fowl (Numida meleagris) lateral gastrocnemius (LG) to the in vivo operating range during walking and running. We test the hypothesis that muscle fascicles operate on the F-L plateau, near the optimal length for force (L0) and near velocities that maximize power output (Vopt) during walking and running. We found that in vivo LG velocities are consistent with optimizing power during work production, and economy of force at higher loads. However, LG does not operate near L0 at higher loads. LG length was near L0 at the time of electromyography (EMG) onset but shortened rapidly such that force development during stance occurred on the ascending limb of the F-L curve, around 0.8L0. Shortening across L0 in late swing might optimize potential for rapid force development near the swing-stance transition, providing resistance to unexpected perturbations that require rapid force development. We also found evidence of in vivo passive force rise in late swing, without EMG activity, at lengths where in situ passive force is zero, suggesting that dynamic viscoelastic effects contribute to in vivo force development. Comparison of in vivo operating ranges with F-L and F-V properties suggests the need for new approaches to characterize muscle properties in controlled conditions that more closely resemble in vivo dynamics.

A meta-analysis of whole-body and heart mass effect sizes from a long-term artificial selection experiment for high voluntary exercise.

Selection experiments play an increasingly important role in comparative and evolutionary physiology. However, selection experiments can be limited by relatively low statistical power, in part because replicate line is the experimental unit for analyses of direct or correlated responses (rather than number of individuals measured). One way to increase the ability to detect correlated responses is through a meta-analysis of studies for a given trait across multiple generations. To demonstrate this, we applied meta-analytic techniques to two traits (body mass and heart ventricle mass, with body mass as a covariate) from a long-term artificial selection experiment for high voluntary wheel-running behavior. In this experiment, all four replicate High Runner (HR) lines reached apparent selection limits around generations 17-27, running approximately 2.5- to 3-fold more revolutions per day than the four non-selected Control (C) lines. Although both traits would also be expected to change in HR lines (relative heart size expected to increase, expected direction for body mass is less clear), their statistical significance has varied, despite repeated measurements. We compiled information from 33 unique studies and calculated a measure of effect size (Pearson's R). Our results indicate that, despite a lack of statistical significance in most generations, HR mice have evolved larger hearts and smaller bodies relative to controls. Moreover, plateaus in effect sizes for both traits coincide with the generational range during which the selection limit for wheel-running behavior was reached. Finally, since reaching the selection limit, absolute effect sizes for body mass and heart ventricle mass have become smaller (i.e. closer to 0).