One-week quercetin intervention modifies motor unit recruitment patterns before and during resistance exercise in older adults: A randomized controlled trial.

We investigated the effects of one-week quercetin ingestion on motor unit (MU) behavior and muscle contractile properties before, during, and after a single session of resistance exercise in older adults. Twenty-four older adults were divided into two groups: those receiving quercetin glycosides (QUE) or placebo (PLA), and they performed a single session of resistance exercise. MU behavior before and during resistance exercise and electrically elicited contraction before and after resistance exercise were measured (Day 1), and the same measurements were conducted again after 7 days of placebo or quercetin glycoside ingestion (Day 8). The MU recruitment threshold (RT) was decreased (p < 0.001, 25.6 ± 10.1 to 23.6 ± 9.5 %MVC) and the exerted force normalized by the MU firing rate (FR) was increased (p = 0.003, 1.13 ± 0.24 to 1.18 ± 0.22 %MVC/pps) from Days 1 to 8, respectively, in QUE but not PLA (p = 0.263, 22.6 ± 11.9 to 21.9 ± 11.6 %MVC; p = 0.713, 1.09 ± 0.20 to 1.10 ± 0.19 %MVC/pps, respectively). On Day 1, a significant correlation between MURT and%change in MUFR from the first to last contractions during the resistance exercise was observed in both groups (QUE: p = 0.009, rs = 0.308; PLA: p < 0.001, rs = 0.403). On Day 8 %change in MUFR was negatively correlated with MURT in QUE (p = 0.044, rs = -0.251), but there was no significant correlation in PLA (p = 0.844). There was no difference in electrically elicited contraction before and after the resistance exercise between QUE and PLA (p < 0.05). These results suggest that one-week quercetin ingestion in older adults lowered MURT and led to greater fatigue in MU with higher RT than with lower RT during resistance training.

Acute effects of caffeine or quercetin ingestion on motor unit firing pattern before and after resistance exercise.

The aim of the present study was to investigate the acute effect of caffeine or quercetin ingestion on motor unit firing patterns and muscle contractile properties before and after resistance exercise. High-density surface electromyography (HDs-EMG) during submaximal contractions and electrically elicited torque in knee extensor muscles were measured before (PRE) and 60 min after (POST1) ingestion of caffeine, quercetin glycosides, or placebo, and after resistance exercise (POST2) in ten young males. The Convolution Kernel Compensation technique was used to identify individual motor units of the vastus lateralis muscle for the recorded HDs-EMG. Ingestion of caffeine or quercetin induced significantly greater decreases in recruitment thresholds (RTs) from PRE to POST1 compared with placebo (placebo: 94.8 ± 9.7%, caffeine: 84.5 ± 16.2%, quercetin: 91.9 ± 36.7%), and there were significant negative correlations between the change in RTs (POST1-PRE) and RT at PRE for caffeine (rs = - 0.448, p < 0.001) and quercetin (rs = - 0.415, p = 0.003), but not placebo (rs = - 0.109, p = 0.440). Significant positive correlations between the change in firing rates (POST2-POST1) and RT at PRE were noted with placebo (rs = 0.380, p = 0.005) and quercetin (rs = 0.382, p = 0.007), but not caffeine (rs = 0.069, p = 0.606). No significant differences were observed in electrically elicited torque among the three conditions. These results suggest that caffeine or quercetin ingestion alters motor unit firing patterns after resistance exercise in different threshold-dependent manners in males.

Association between physical fitness tests and neuromuscular properties.

PURPOSE: While various fitness tests have been developed to assess physical performances, it is unclear how these tests are affected by differences, such as, in morphological and neural factors. This study was aimed to investigate associations between individual differences in physical fitness tests and neuromuscular properties. METHODS: One hundred and thirty-three young adults participated in various general physical fitness tests and neuromuscular measurements. The appendicular skeletal muscle mass (ASM) was estimated by bioelectrical impedance analysis. Echo intensity (EI) was evaluated from the vastus lateralis. During submaximal knee extension force, high-density surface electromyography of the vastus lateralis was recorded and individual motor unit firings were detected. Y-intercept (i-MU) and slope (s-MU) from the regression line between the recruitment threshold and motor unit firing rate were calculated. RESULTS: Stepwise multiple regression analyses revealed that knee extension strength could be explained (adjusted R2 = 0.712) by ASM (ß = 0.723), i-MU (0.317), EI (- 0.177), and s-MU (0.210). Five-sec stepping could be explained by ASM (adjusted R2 = 0.212). Grip strength, side-stepping, and standing broad jump could be explained by ASM and echo intensity (adjusted R2 = 0.686, 0.354, and 0.627, respectively). Squat jump could be explained by EI (adjusted R2 = 0.640). Counter-movement jump could be explained by EI and s-MU (adjusted R2 = 0.631). On the other hand, i-MU and s-MU could be explained by five-sec stepping and counter-movement jump, respectively, but the coefficients of determination were low (adjusted R2 = 0.100 and 0.045). CONCLUSION: Generally developed physical fitness tests were mainly explained by morphological factors, but were weakly affected by neural factors involved in performance.

Can Neuromuscular Electrical Stimulation Enhance the Effect of Sprint Interval Training?

The aim of this study was to determine the effects of subtetanic neuromuscular electrical stimulation combined with voluntary exercise between repeated Wingate tests on sprint exercise performance and blood lactate accumulation during sprint interval training. Fifteen healthy young males volunteered. After 1-min baseline, participants underwent the Wingate test twice. They performed a 4-min intervention between tests: neuromuscular electrical stimulation with free-weight cycling or voluntary cycling alone [43.6 (8.0) watts], which matched oxygen consumption with neuromuscular electrical stimulation with free-weight cycling. The blood lactate concentration was assessed at the end of the baseline, at 3-min intervention, and on recovery at 1, 3, 5, and 10 min after the second Wingate test. Peak and mean blood lactate concentration during recovery were significantly greater with neuromuscular electrical stimulation with free-weight cycling than voluntary cycling alone (P>0.036 and P=0.011, respectively). Peak power, mean power, and rate of decline (fatigue index) were not significantly different between conditions in both Wingate tests (condition/interaction all P>0.300, partial η2<0.1). Subtetanic neuromuscular electrical stimulation combined with voluntary exercise indicated similar exercise performance and fatigue levels during Wingate tests, but enhanced blood lactate accumulation compared to oxygen consumption-matched voluntary cycling during sprint interval training.

Time-of-day effects on motor unit firing and muscle contractile properties in humans.

Intrinsic factors related to neuromuscular function are time-of-day dependent, but diurnal rhythms in neural and muscular components of the human neuromuscular system remain unclear. The present study aimed to investigate the time-of-day effects on neural excitability and muscle contractile properties by assessing the firing properties of tracked motor units and electrically evoked twitch muscle contraction. In 15 young adults (22.9 ± 4.7 yr), neuromuscular function was measured in the morning (10:00), at noon (13:30), in the evening (17:00), and at night (20:30). Four measurements were completed within 24 h. The measurements consisted of maximal voluntary contraction (MVC) strength of knee extension, recording of high-density surface electromyography (HDsEMG) from the vastus lateralis during ramp-up contraction to 50% of MVC, and evoked twitch torque of knee extensors by electrical stimulation. Recorded HDsEMG signals were decomposed to individual motor unit firing behaviors and the same motor units were tracked among the times of day, and recruitment thresholds and firing rates were calculated. The number of detected and tracked motor units was 127. Motor unit firing rates significantly increased from morning to noon, evening, and night (P < 0.01), but there were no significant differences in recruitment thresholds among the times of day (P > 0.05). Also, there were no significant effects of time of day on evoked twitch torque (P > 0.05). Changes in the motor unit firing rate and evoked twitch torque were not significantly correlated (P > 0.05). These findings suggest that neural excitability may be affected by the time of day, but it did not accompany changes in peripheral contractile properties in a diurnal manner.NEW & NOTEWORTHY We investigated the variations of tracked motor unit firing properties and electrically evoked twitch contraction during the day within 24 h. The variation of motor unit firing rate was observed, and tracked motor unit firing rate increased at noon, in the evening, and at night compared with that in the morning. The variation in motor unit firing rate was independent of changes in twitch contraction. Motor unit firing rate may be affected by diurnal rhythms.

Motor Unit Firing Properties During Force Control Task and Associations With Neurological Tests in Children.

The present study aimed to clarify the development of motor unit (MU) firing properties and the association between those neural properties and force steadiness (FS)/neurological tests in 6- to 12-year-old children. Fifty-eight school-aged children performed maximal voluntary knee extension contraction, a submaximal FS test at 10% of maximal voluntary knee extension contraction, knee extension reaction time to light stimulus test, and single-leg standing test, and data from 38 children who passed the criteria were subject to analysis. During the FS test, high-density surface electromyography was recorded from the vastus lateralis muscle to identify individual MU firing activity. FS was improved with an increase in age (r = -.540, P < .001). The MU firing rate (MUFR) was significantly decreased with an increase in age (r = -.343, P = .035). MUFR variability was not associated with age. Although there was no significant correlation between FS and MUFR, FS was significantly correlated with MUFR variability even after adjustment for the effect of age (r = .551, P = .002). Neither the reaction time nor the single-leg standing test was correlated with any MU firing properties. These findings suggest that MUFR variability makes an important contribution to precise force control in children but does not naturally develop with age.

Subtetanic neuromuscular electrical stimulation can maintain Wingate test performance but augment blood lactate accumulation.

PURPOSE: Concentration- and time-dependent effect of lactate on physiological adaptation (i.e., glycolytic adaptation and mitochondrial biogenesis) have been reported. Subtetanic neuromuscular electrical stimulation (NMES) with voluntary exercise (VOLES) can increase blood lactate accumulation. However, whether this is also true that VOLES can enhance the blood lactate accumulation during sprint exercise is unknown. Thus, we investigated whether VOLES before the Wingate test can enhance blood lactate accumulation without compromising Wingate exercise performance. METHODS: Fifteen healthy young males (mean [SD], age: 23 [4] years, body mass index: 22.0 [2.1] kg/m2) volunteered. After resting measurement, participants performed a 3-min intervention: VOLES (NMES with free-weight cycling) or voluntary cycling alone, which matched exercise intensity with VOLES (VOL, 43.6 [8.0] watt). Then, they performed the Wingate test with 30 min free-weight cycling recovery. The blood lactate concentration ([La]b) was assessed at the end of resting and intervention, and recovery at 1, 3, 5, 10, 20, and 30 min. RESULTS: [La]b during intervention was higher with VOLES than VOL (P = 0.011). The increase in [La]b after the Wingate test was maintained for longer with VOLES than VOL at 10- and 20-min recovery (P = 0.014 and 0.023, respectively). Based on the Wingate test, peak power, mean power, and the rate of decline were not significantly different between VOLES and VOL (P = 0.184, 0.201, and 0.483, respectively). CONCLUSION: The combination of subtetanic NMES with voluntary exercise before the Wingate test has the potential to enhance blood lactate accumulation. Importantly, this combined approach does not compromise Wingate exercise performance compared to voluntary exercise alone.

Prediction of 1-year change in knee extension strength by neuromuscular properties in older adults.

Improving muscle strength and preventing muscle weakness are important for older adults. The change in strength can be effectively explained by skeletal muscle mass and neural factors. Neural factors are important for older adults because the variation of neural components is greater in older than in young adults, and any decline in strength cannot solely be explained by a decrease in skeletal muscle mass. The purpose of the present study was to investigate whether skeletal muscle mass or motor unit firing properties could explain the change in muscle strength after 1 year. Thirty-eight older adults (75.0 ± 4.7 years, 156.6 ± 7.7 cm, 55.5 ± 9.4 kg, 26 women) performed maximum voluntary knee extension and their skeletal muscle mass was measured using a bioimpedance device. During a submaximal contraction task, high-density surface electromyography was recorded and the signals were decomposed into individual motor unit firing. As an index of motor unit firing properties, the slope and y-intercept (MU intercept) were calculated from the regression line between recruitment thresholds and firing rates in each participant. After 1 year, their maximum knee extension torque was evaluated again. A stepwise multiple regression linear model with sex and age as covariates indicated that MU intercept was a significant explanation with a negative association for the 1-year change in muscle strength (ß = - 0.493, p = 0.004), but not skeletal muscle mass (p = 0.364). The results suggest that neural components might be predictors of increasing and decreasing muscle strength rather than skeletal muscle mass.

Effects of 7-day quercetin intervention on motor unit activity and muscle contractile properties before and after resistance exercise in young adults randomized controlled trials.

We investigated whether the alteration of the motor unit recruitment threshold (MURT) caused by quercetin ingestion intervention for 7 days modifies motor unit activation patterns before and after a single session of resistance exercise. Twenty young male and female adults were divided into two groups: ingestion of placebo (PLA) or quercetin glycosides at 200 mg/day (QUE). High-density surface electromyography during submaximal contractions was measured to assess the motor unit firing rate (MUFR) and MURT of the vastus lateralis muscle before (PRE) and after (POST) resistance exercise (DAY1). The same measurements were repeated after 7 days of placebo or quercetin glycoside ingestion (DAY8). In QUE, MURT decreased more from DAY1-PRE to DAY8-PRE (29.1 ± 9.1 to 27.1 ± 9.5% MVC, p < 0.001) but not in PLA (29.8 ± 10.4 to 28.9 ± 9.7% MVC, p < 0.167). For percentage change in MUFR following resistance exercise, there was a significant interaction (day × group, p < 0.001). The degree of changes in MURT from DAY1-PRE to DAY8-PRE was significantly correlated with the percentage change of MUFR from DAY8-PRE to DAY8-POST in QUE (p = 0.014, r = -0.363) but not in PLA (p = 0.518). The study suggests that 7-day quercetin ingestion alters the motor unit recruitment pattern, and this may induce changes in motor unit firing patterns during a single session of resistance training (Trial registration: UMIN000052255, R000059650).

Impact of subtetanic neuromuscular electrical stimulation on cardiac autonomic nervous system in young individuals.

BACKGROUND: Although subtetanic neuromuscular electrical stimulation (NMES) has been proposed as an exercise training and/or rehabilitation tool, the impact of NMES on the autonomic nervous system (ANS) is unclear. Thus, we hypothesized that NMES would alter ANS, i.e., increase sympathetic activity and decrease parasympathetic activity, in young individuals. METHODS: Eighteen healthy young individuals (16 males, mean age: 22 [SD: 4] years, Body Mass Index: 21.7 [2.2] kg/m2) volunteered. Blood pressure (BP), heart rate (HR), and R-R intervals were recorded during 6-minute resting, NMES, and recovery conditions. Short-term heart rate variability analysis of R-R intervals was performed for the frequency and time domains during each condition. Time domain indices included the root mean square of successive R-R interval differences (RMSSD), and the percentage of successive R-R intervals differing by more than 50ms (pRR50%). Frequency domain indices (fast Fourier transform) of R-R intervals included total power (TP), low-frequency (LF) power (0.04-0.15 Hz), and high-frequency (HF) power (0.15-0.4 Hz). RESULTS: BP was not altered but HR was significantly increased during NMES (P<0.001), and it returned to the resting level at recovery. RMSSD and pRR50 decreased from resting to NMES and returned at recovery conditions (P<0.05, respectively). TP and HF decreased from resting to NMES and returned at recovery conditions (P<0.05, respectively). LF increased from NMES to recovery (P<0.05). The LF/HF ratio showed no significant differences between conditions (P=0.210). CONCLUSIONS: Cardiac ANS fluctuated by subtetanic NMES without BP elevation in healthy young individuals. Parasympathetic but not sympathetic activity was affected by NMES stimulation.

Differences in acute neuromuscular response after single session of resistance exercise between young and older adults.

AIMS: The purpose of this study was to investigate differences in the acute response after resistance exercise between young and older adults. METHODS: Seventeen young and 18 older adults performed a single session of resistance exercise, consisting of 3 sets of 10 isometric knee extensions. Maximal voluntary contraction (MVC), motor unit (MU) activity of the vastus lateralis, and electrically elicited torque of the knee extensor were measured before and after the resistance exercise. RESULTS: Although both groups showed the same degree of decline in MVC (young: -15.2 ± 14.3 %, older: -16.4 ± 7.9 %, p = 0.839), electrically elicited torque markedly decreased in the young group (young: -21.5 ± 7.7 %, older: -14.3 ± 9.5 %, p < 0.001), and the decrease in the MU firing rate was greater in the older group (young: -26.1 ± 24.1 %, older: -44.7 ± 24.5 %, p < 0.001). Changes in the MU firing rate following the exercise were correlated with the MU recruitment threshold in the older group (p < 0.001, rs = 0.457), but not young group (p = 0.960). DISCUSSION: These results showed that young adults exhibited a greater acute response in the peripheral component, whereas older adults showed a greater acute response in the central component of the neuromuscular system, and the acute response in MUs with a high recruitment threshold following resistance exercise was smaller than in those with a low recruitment threshold in older adults. These findings may partly explain why there are different chronic adaptations to resistance training between young and older adults.

Characterization of TRPM8-expressing neurons in the adult mouse hypothalamus.

Transient receptor potential melastatin 8 (TRPM8) is a menthol receptor that detects cold temperatures and influences behaviors and autonomic functions under cold stimuli. Despite the well-documented peripheral roles of TRPM8, the evaluation of its central functions is still of great interest. The present study clarifies the nature of a subpopulation of TRPM8-expressing neurons in the adult mice. Combined in situ hybridization and immunohistochemistry revealed that TRPM8-expressing neurons are exclusively positive for glutamate decarboxylase 67 mRNA signals in the lateral septal nucleus (LS) and preoptic area (POA) but produced no positive signal for vesicular glutamate transporter 2. Double labeling immunohistochemistry showed the colocalization of TRPM8 with vesicular GABA transporter at axonal terminals. Immunohistochemistry further revealed that TRPM8-expressing neurons frequently expressed calbindin and calretinin in the LS, but not in the POA. TRPM8-expressing neurons in the POA expressed a prostaglandin E2 receptor, EP3, and neurotensin, whereas expression in the LS was minimal. These results indicate that hypothalamic TRPM8-expressing neurons are inhibitory GABAergic, while the expression profile of calcium-binding proteins, neurotensin, and EP3 differs between the POA and LS.

Longitudinal development of muscle strength and relationship with motor unit activity and muscle morphological characteristics in youth athletes.

Neural and morphological adaptations determine gains of muscle strength. For youth athletes, the importance of morphological adaptation is typically highlighted based on the change in maturity status. However, the long-term development of neural components in youth athletes remains unclear. The present study investigated the longitudinal development of muscle strength, muscle thickness (MT), and motor unit firing activity of the knee extensor and their relationships in youth athletes. Seventy male youth soccer players (mean ± SD age = 16.3 ± 0.6 years) performed neuromuscular, maximal voluntary isometric contraction (MVC), and submaximal ramp contraction (at 30 and 50% MVC) tests with knee extensors, two times with a 10-month measurement interval. High-density surface electromyography was recorded from the vastus lateralis and decomposed to identify each individual motor unit activity. MT was evaluated by the sum of the vastus lateralis and vastus intermedius thicknesses. Finally, sixty-four participants were employed to compare MVC and MT, and 26 participants were employed to analyze motor unit activity. MVC and MT were increased from pre to post (p < 0.05, 6.9 and 1.7% for MVC and MT, respectively). Y-intercept of the regression line between median firing rate vs. recruitment threshold was also increased (p < 0.05, 13.3%). Multiple regression analysis demonstrated that the gains of both MT and Y-intercept were explanatory variables for the gain of strength. These findings suggest that the neural adaptation could also make the important contribution to the strength gain for the youth athletes over a 10-month training period.

Crystal structure of the 13-cis isomer of bacteriorhodopsin in the dark-adapted state.

The atomic structure of the trans isomer of bacteriorhodopsin was determined previously by using a 3D crystal belonging to the space group P622. Here, a structure is reported for another isomer with the 13-cis, 15-syn retinal in a dark-adapted crystal. Structural comparison of the two isomers indicates that retinal isomerization around the C13[double bond]C14 and the C15[double bond]N bonds is accompanied by noticeable displacements of a few residues in the vicinity of the retinal Schiff base and small re-arrangement of the hydrogen-bonding network in the proton release channel. On the other hand, aromatic residues surrounding the retinal polyene chain were found to scarcely move during the dark/light adaptation. This result suggests that variation in the structural rigidity within the retinal-binding pocket is one of the important factors ensuring the stereospecific isomerization of retinal.

Crystal structure of the L intermediate of bacteriorhodopsin: evidence for vertical translocation of a water molecule during the proton pumping cycle.

For structural investigation of the L intermediate of bacteriorhodopsin, a 3D crystal belonging to the space group P622 was illuminated with green light at 160 K and subsequently with red light at 100 K. This yielded a approximately 1:4 mixture of the L intermediate and the ground-state. Diffraction data from such crystals were collected using a low flux of X-rays ( approximately 2 x 10(15) photons/mm2 per crystal), and their merged data were compared with those from unphotolyzed crystals. These structural data, together with our previous data, indicate that the retinal chromophore, which is largely twisted in the K-intermediate, takes a more planar 13-cis, 15-anti configuration in the L intermediate. This configurational change, which is accompanied by re-orientation of the Schiff base N-H bond towards the intracellular side, is coupled with a large rotation of the side-chain of an amino acid residue (Leu93) making contact with the C13 methyl group of retinal. Following these motions, a water molecule, at first hydrogen-bonded to the Schiff base and Asp85, is dragged to a space that is originally occupied by Leu93. Diffraction data from a crystal containing the M intermediate showed that this water molecule moves further towards the intracellular side in the L-to-M transition. It is very likely that detachment of this water molecule from the protonated Schiff base causes a significant decrease in the pKa of the Schiff base, thereby facilitating the proton transfer to Asp85. On the basis of these observations, we argue that the vertical movement of a water molecule in the K-to-L transition is a key event determining the directionality of proton translocation in the protein.