Chronic, acute and protocol-dependent effects of exercise on psycho-physiological health during long-term isolation and confinement.

Exercise could prevent physical and psychological deteriorations, especially during pandemic times of lock-down scenarios and social isolation. But to meet both, the common exercise protocols require optimization based on holistic investigations and with respect to underlying processes. This study aimed to explore individual chronic and acute effects of continuous and interval running exercise on physical and cognitive performance, mood, and affect and underlying neurophysiological factors during a terrestrial simulated space mission. Six volunteers (three females) were isolated for 120 days. Accompanying exercise training consisted of a continuous and interval running protocol in a cross-over design. Incremental stage tests on a treadmill were done frequently to test physical performance. Actigraphy was used to monitor physical activity level. Cognitive performance, mood (MoodMeter®), affect (PANAS), brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), vascular-endothelial growth factor (VEGF), and saliva cortisol were investigated prior to, four times during, and after isolation, pre- and post-exercise on two separate days, respectively. As a chronic effect, physical performance increased (and IGF-1 tended) in the course of isolation and training until the end of isolation. Subjective mood and affect state, as well as cognitive performance, basal BDNF and VEGF levels, were well-preserved across the intervention. No acute effects of exercise were detected, besides slower reaction time after exercise in two out of nine cognitive tests, testing sensorimotor speed and memory of complex figures. Consistently higher basal IGF-1 concentrations and faster reaction time in the psychomotor vigilance test were found for the continuous compared to the interval running protocol. The results suggest that 120 days of isolation and confinement can be undergone without cognitive and mental deteriorations. Regular, individual aerobic running training supporting physical fitness is hypothesized to play an important role in this regard. Continuous running exercise seems to trigger higher IGF-1 levels and vigilance compared to interval running. Systematic and prolonged investigations and larger sample size are required to follow up on exercise-protocol specific differences in order to optimize the exercise intervention for long-term psycho-physiological health and well-being.

Executive control processes are associated with individual fitness outcomes following regular exercise training: blood lactate profile curves and neuroimaging findings.

Cardiovascular training has been associated with neuroimaging correlates of executive control functions (ECF) in seniors and children/adolescents, while complementary studies in middle-aged populations are lacking. Ascribing a prominent role to cardiorespiratory fitness improvements, most studies concentrated on training-induced gains in maximal oxygen uptake (VO2max), although other fitness indices may provide complementary information. Here, we investigated the impact of long-term sub-maximal exercise training on interference control, considering individual training-induced shifts in blood lactate profile curves (BLC) and VO2max. Twenty-three middle-aged sedentary males (M = 49 years) underwent a six-month exercise program (intervention group, IG). Additionally, 14 individuals without exercise training were recruited (control group, CG, M = 52 years). Interference control was assessed before and after the intervention, using a functional magnetic resonance imaging (fMRI) flanker paradigm. Task performance and brain activations showed no significant group-by-time interactions. However, regression analyses in the IG revealed significant associations between individual fitness gains and brain activation changes in frontal regions, which were not evident for VO2max, but for BLC. In conclusion, training-induced plasticity of ECF-related brain activity can be observed in late middle adulthood, but depends on individual fitness gains. For moderate training intensities, BLC shifts may provide sensitive markers for training-induced adaptations linked to ECF-related brain function.

The effects of exercise intensity and post-exercise recovery time on cortical activation as revealed by EEG alpha peak frequency.

Acute physical exercise (APE) induces an increase in the individual alpha peak frequency (iAPF), a cortical parameter associated with neural information processing speed. The aim of this study was to further scrutinize the influence of different APE intensities on post-exercise iAPF as well as its time course after exercise cessation. 95 healthy young (18-35 years) subjects participated in two randomized controlled experiments (EX1 and EX2). In EX1, all participants completed a graded exercise test (GXT) until exhaustion and were randomly allocated into different delay groups (immediately 0, 30, 60 and 90 min after GXT). The iAPF was determined before, immediately after as well as after the group-specific delay following the GXT. In EX2, participants exercised for 35 min at either 45-50%, 65-70% or 85-90% of their maximum heart rate (HRmax). The iAPF was determined before, immediately after as well as 20 min after exercise cessation. In EX1, the iAPF was significantly increased immediately after the GXT in all groups. This effect was not any more detectable after 30 min following exercise cessation. In EX2, a significant increase of the iAPF was found only after high-intensity (85-90% HRmax) exercise. The results indicate intense or exhaustive physical exercise is required to induce a transient increase in the iAPF that persists about 30 min following exercise cessation. Based on these findings, further research will have to scrutinize the behavioral implications associated with iAPF modulations following exercise.

Velocity-specific and time-dependent adaptations following a standardized Nordic Hamstring Exercise training.

The Nordic Hamstring Exercise (NHE) is effective for selective hamstring strengthening to improve muscle balance between knee flexors and extensors. The purpose of this study (within subject design of repeated measures) was to determine the effects of a standardized 4-week NHE training on thigh strength and muscle balance with concomitant kinetic and kinematic monitoring. Sixteen male sprinters (22 years, 181 cm, 76 kg) performed a standardized 4-week NHE training consisting of three sessions per week (each 3×3 repetitions). Six rope-assisted and six unassisted sessions were performed targeting at a constant knee extension angular velocity of ~15°/s across a ~90-100° knee joint range of motion. Kinetic (peak and mean moment, impulse) and kinematic parameters (eg, ROM to downward acceleration, ROMDWA ) were recorded during selected sessions. Unilateral isokinetic tests of concentric and eccentric knee flexors and extensors quantified muscle group-, contraction mode-, and velocity-specific training adaptations. Peak moments and contractional work demonstrated strong interactions of time with muscle group, contraction modes, and angular velocities (η²>.150). NHE training increased eccentric hamstring strength by 6%-14% as well as thigh muscle balance with biggest adaptations at 150°/s 2 weeks after NHE training. Throughout the training period significant increases (P<.001) of peak (η²=.828) and mean moments (η²=.611) became apparent, whereas the impulse and the ROMDWA of unassisted NHE repetitions remained unchanged (P>.05). A 4-week NHE training significantly strengthened the hamstrings and improved muscle balance between knee flexors and extensors. Despite the slow training velocity, biggest adaptations emerged at the highest velocity 2 weeks after training ended.

The impact of long-term confinement and exercise on central and peripheral stress markers.

Long-term isolation has been reported to have impact on psycho-physiological performance in humans. As part of the 520 days isolation study (MARS500, n=6) from June 3rd 2010 to November 4th 2011, this study aimed to show that stress caused by isolation and confinement is mirrored in cortical activity and cortisol levels and that exercise is a valid countermeasure. Cortical activity was measured by electroencephalography (EEG) pre- and post-moderate exercise every two weeks, salivary cortisol was taken every 60 days. Data show a decrease of global cortical activity, in both alpha- and beta-activity (p<.05-p<.001), and an increase of salivary cortisol (p<.05-p<.001), during the isolation, indicating that isolation acts as a chronic stressor with impact on cortical activity and cortisol levels. Moderate exercise leads to an increase (p<.01) in cortical activity. Therefore, during long-term space missions the factor isolation must be kept in mind as the reduction of cortical activity and the heightened stress level could impair performance. However moderate exercise might be able to counteract this impairment.

Cortical processes associated with continuous balance control as revealed by EEG spectral power.

Balance is a crucial component in numerous every day activities such as locomotion. Previous research has reported distinct changes in cortical theta activity during transient balance instability. However, there remains little understanding of the neural mechanisms underlying continuous balance control. This study aimed to investigate cortical theta activity during varying difficulties of continuous balance tasks, as well as examining the relationship between theta activity and balance performance. 37 subjects completed nine balance tasks with different levels of surface stability and base of support. Throughout the balancing task, electroencephalogram (EEG) was recorded from 32 scalp locations. ICA-based artifact rejection was applied and spectral power was analyzed in the theta frequency band. Theta power increased in the frontal, central, and parietal regions of the cortex when balance tasks became more challenging. In addition, fronto-central and centro-parietal theta power correlated with balance performance. This study demonstrates the involvement of the cerebral cortex in maintaining upright posture during continuous balance tasks. Specifically, the results emphasize the important role of frontal and parietal theta oscillations in balance control.

Cortical current density oscillations in the motor cortex are correlated with muscular activity during pedaling exercise.

Despite modern imaging techniques, assessing and localizing changes in brain activity during whole-body exercise is still challenging. Using an active electroencephalography (EEG) system in combination with source localization algorithms, this study aimed to localize brain cortical oscillations patterns in the motor cortex and to correlate these with surface electromyography (EMG)-detected muscular activity during pedaling exercise. Eight subjects performed 2-min isokinetic (90 rpm) cycling bouts at intensities ranging from 1 to 5 Wkg(-1) body mass on a cycle ergometer. These bouts were interspersed by a minimum of 2 min of passive rest to limit to development of peripheral muscle fatigue. Brain cortical activity within the motor cortex was analyzed using a 32-channel active EEG system combined with source localization algorithms. EMG activity was recorded from seven muscles on each lower limb. EEG and EMG activity revealed comparatively stable oscillations across the different exercise intensities. More importantly, the oscillations in cortical activity within the motor cortex were significantly correlated with EMG activity during the high-intensity cycling bouts. This study demonstrates that it is possible to localize oscillations in brain cortical activity during moderate- to high-intensity cycling exercise using EEG in combination with source localization algorithms, and that these oscillations match the activity of the active muscles in time and amplitude. Results of this study might help to further evaluate the effects of central vs. peripheral fatigue during exercise.

Influences of exercise and training on the circulating concentration of prolactin in humans.

Physical activity has an impact on several endocrine functions. During exercise, certain endocrine adjustments are required to maintain the homeostasis. It is well known that, depending on the intensity and duration, exercise stimulates the release of the hormone prolactin (PRL). After the cessation of acute exercise, this effect persist and continues during the recovery period. Chronic exercise can affect the PRL basal concentration and/or the PRL response to acute exercise. The main functions of PRL are associated with the maintenance of homeostasis and processes of reproduction. A role for PRL also has been recognised as an important regulator of cellular proliferation. The present review examines the exercise-induced acute or adaptive responses of PRL secretion. It is also hypothesised that increased concentrations of PRL during exercise could play an important role for neuroplasticity as a result of involvement of the hormone in the neurogenesis in subventricular zone of the adult brain.

pH buffering does not influence BDNF responses to exercise.

The influence of acidosis on brain-derived neurotrophic factor (BDNF) was examined by buffering pH changes during 10 min of continuous low intensity (LIE) and following high intensity cycling exercise to exhaustion (HIE). 11 athletes participated in 2 trials separated by 1 week. Individuals received either a placebo infusion (isotonic saline) or an isotonic sodium bicarbonate infusion before and during exercise. Blood samples were drawn at rest, after LIE and after HIE, as well as 3, 6, 10 and 15 min post exercise. During placebo trial, HIE induced a profound decrease (p<0.01) of capillary blood bicarbonate concentration (HCO3-), pH, base excess (BE) and pCO2. Higher (p<0.01) HCO3-, pH and BE were found during bicarbonate infusion and post exercise in comparison to the placebo trial. Exercise induced an identical increase of blood lactate concentration in both trials. Serum BDNF concentration was increased (p<0.01) at the end of HIE and remained elevated until 3 min post exercise in both trials. The present study suggests that during HIE lactate might have an acidosis-independed impact on BDNF secretion because buffering of blood gases, that attenuate the fall of pH but not the accumulation of lactic acid, failed to alter the exercise-induced increase of BDNF.

MSTN mRNA after varying exercise modalities in humans.

The aim of this study was to examine the effects of strength and endurance training on myostatin mRNA in the vastus lateralis muscle of healthy and physically active humans. 21 healthy and physically active sports students (static and dynamic knee extensor strength 33 ± 4.5 N/kgBW; 1 185 ± 170 W, respectively; maximum oxygen uptake 52.5 ± 8 ml/kgBW/min) were recruited and randomly assigned to a moderate endurance training group (n=7), a strength training group (n=7) and a control group (n=7). Muscle biopsies were taken from the vastus lateralis muscle 3-5 days before the start as well as at the end of the 12 weeks' training period. Exercise-specific functional improvements after moderate endurance training and strength training were measured for submaximal endurance and for static and dynamic strength of the knee extensor muscles. None of the myostatin mRNA values showed significant pre-post differences or group-specific differences. These results are in contrast to data with sedentary subjects, suggesting that myostatin is necessary for adaptations of skeletal muscle to exercise stress. We conclude that functional improvements after moderate endurance training and strength training can occur without alterations in myostatin mRNA in physically active humans.

Primary motor cortex activity is elevated with incremental exercise intensity.

While the effects of exercise on brain cortical activity from pre-to post-exercise have been thoroughly evaluated, few studies have investigated the change in activity during exercise. As such, it is not clear to what extent changes in exercise intensity influence brain cortical activity. Furthermore, due to the difficulty in using brain-imaging methods during complex whole-body movements like cycling, it is unclear to what extent the activity in specific brain areas is altered with incremental exercise intensity over time. Latterly, active electroencephalography (EEG) electrodes combined with source localization methods allow for the assessment of brain activity, measured as EEG current density, within specific cortical regions. The present study aimed to investigate the application of this method during exercise on a cycle ergometer, and to investigate the effect of increasing exercise intensity on the magnitude and location of any changes in electrocortical current density. Subjects performed an incremental cycle ergometer test until subjective exhaustion. Current density of the EEG recordings during each test stage, as well as before and after exercise, was determined. Spatial changes in current density were localized using low-resolution brain electromagnetic tomography (LORETA) to three regions of interest; the primary motor cortex, primary sensory cortex and prefrontal cortex, and were expressed relative to current density within the local lobe. It was demonstrated that the relative current density of the primary motor cortex was intensified with increasing exercise intensity, whereas activity of the primary sensory cortex and that of the prefrontal cortex were not altered with exercise. The results indicate that the combined active EEG/LORETA method allows for the recording of brain cortical activity during complex movements and incremental exercise. These findings indicate that primary motor cortex activity is elevated with incremental exercise intensity during a whole-body movement, like cycling.

Effect of resistance exercise on serum levels of growth factors in humans.

Studies have shown that, depending on intensity, endurance exercise increases neurotrophins and thereby induces neuroplasticity. However, data on the effect of acute resistance exercise at different intensities on neurotrophins is not yet available. Thus, we conducted 2 trials to determine the serum concentrations of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin-like growth factor (IGF-1) before and after a low or high intensity resistance exercise in 11 healthy humans. Exercise load was related to 3 repetitions of maximal effort isokinetic work involving knee extension under alternating concentric and eccentric conditions for muscle work at a velocity of 60°s-1 registered during a familiarization session. The torque angle diagrams from these 3 repetitions were averaged and displayed as target curves in the test sessions, the intensity of resistance exercise was set at 40% (trial: R1) or 110% (trial: R2) of the averaged individual maximal effort curve, respectively. After resistance exercise, serum IGF-1 was increased significantly (p<0.01) by 28% in R1 and 16% in R2 compared to pre-exercise levels. Resistance exercise did not increase serum VEGF at any time point. Serum BDNF increased during exercise compared to post-exercise, but did not achieve significant difference from pre-exercise values. The present study shows that either low or high resistance exercise increases levels of IGF-1, but not of BDNF or VEGF. This finding is of importance for health promotion by means of resistance exercise because circulating serum IGF-1 has been demonstrated to mediate positive effects of exercise on brain functions.

The exercise profile of an ultra-long handcycling race: the Styrkeprøven experience.

BACKGROUND: The high mechanical efficiency of the geared handcycle makes it suitable for elite athletes to train and even compete in races with able-bodied (recreational) cyclists. However, the actual exercise profile for endurance events has not been quantified. OBJECTIVE: To guide future training regimes in a safe and effective process, the aim of this research was to quantify the workload, speed, cadence and heart rate parameters during 6000 km of training and within a 540 km ultra-long races. METHODS: One spinal cord injured participant (lesion level Th4, ASIA B) handcycle (modified Shark S Sopur--Sunrisemedical, Malsch, Germany) was equipped with Schoberer Bike Measurement System (SRM) crank. For the laboratory test, a Cyclus II Ergometer was used. The energy intake and quality was determined during the time of race (540 km). RESULTS: Workload at a defined metabolic situation was augmented through training by 63.8% from 90.0 to 147.6 W. The athlete finished the 540 km race with an average speed of 21.6 km h⁻¹ and a total race time of 38:52 h. CONCLUSIONS: Ultra-long-term races in a handcycle can be suited by well-trained persons with a spinal cord injury. The quality of the training preparation time (for example, intensity and volume) is of immense importance to reach an adequate physiological capacity and to avoid serious injuries or medical problems.

Effects of strength and endurance training on brain-derived neurotrophic factor and insulin-like growth factor 1 in humans.

Blood neurotrophins like insulin-like growth factor (IGF-1) and brain-derived neurotrophic factor (BDNF) are discussed to mediate health benefits of physical activity in humans. The aim of the study was to analyze the training effects of moderate endurance training (Em) and strength training with high loads (Sh) on blood plasma concentrations of IGF-1 and BDNF in humans. Venous blood samples were obtained from 27 healthy students, randomly assigned to an Em, Sh, and a control group, before and after a 12-week training intervention. Sh resulted in an increase in isometric (14.5%) and dynamic (8.3%) strength of the knee extensor muscles in the Sh group and Em led to a significant increase in the endurance performance in the Em group (p<0.05). IGF-1 basal plasma concentrations decreased (p<0.05) after the intervention in all groups. There were no significant changes for BDNF. Despite specific functional adaptations induced by Em and Sh there are no correspondingly different adaptations in the basal blood concentrations of the neurotrophins IGF-1 and BDNF. Additionally, exercise per se does not result in changes in basal plasma concentrations of BDNF, suggesting that the mode of the exercise programme is a decisive factor.

Energy expenditure in ball games for wheelchair users.

PURPOSE: Wheelchair sports have become popular in Germany. This is important because of the difficulty experienced by wheelchair-dependent people in maintaining cardiovascular health and fitness by daily activities. Increasing energy expenditure (EE; kcal h(-1)) is one of the most effective ways of decreasing risk of cardiovascular disease. The purpose of this study was to evaluate the EE of individuals with spinal cord injury in ball games for wheelchair-dependent persons. METHODS: Fourteen tennis players (WT), 10 basketball players (WB) and 12 rugby players (WR) completed a basal metabolism evaluation and a training test to measure respiratory parameters. RESULTS: In the basal metabolism test EE in WT was 66.8+/-12.8 kcal h(-1), in WB 62.7+/-15.0 kcal h(-1) and in WR 63.5+/-12.9 kcal h(-1). During training EE in WT was 325.8+/-73.0 kcal h(-1), in WB 374.8+/-127.1 kcal h(-1) and in WR 248.5+/-69.4 kcal h(-1). The average EE of the whole group was: 316.4+/-89.6 kcal h(-1) with a corresponding heart rate of 118.5+/-23.1 b.p.m. and a lactate concentration of 2.09+/-0.7 mmol l(-1). Statistical analysis showed significantly lower values of EE, heart rate and oxygen uptake for the WR group in comparison to the other groups. CONCLUSION: The results indicate that the additional leisure time EE of persons participating in WB and WT is sufficient to maintain fitness. This level of EE is comparable to the recommendations of the ACSM for able-bodied persons, and therefore might be sufficient to prevent the development of cardiovascular diseases.

Impact of exercise on neuroplasticity-related proteins in spinal cord injured humans.

The present study investigated the effects of exercise on the serum concentrations of brain-derived neurotrophic factor (BDNF), insulin-like growth factor 1 (IGF-1), prolactin (PRL) and cortisol (COR) in 11 chronically spinal cord-injured athletes. In these subjects BDNF concentration at rest was sixfold higher compared with the concentrations reported earlier in able-bodied persons, while IGF-1, PRL and COR were within normal range. Ten minutes of moderate intensity handbiking (54% of the maximal heart rate) during a warm-up period (W) induced an increase (P<0.05) of BDNF of approximately 1.5-fold from basal level at rest, while a decrease to basal level was found after an immediately succeeding handbiking time trial (89% of the maximal heart rate) over the marathon distance of 42 km (M). An increase (P<0.01) of serum IGF-1 was found after W and this levels remained elevated (P<0.01) until the end of M. W had no significant effects on the serum PRL and COR, however, M induced an increase (P<0.01) of both hormones. This is the first study showing elevated BDNF concentrations at rest in spinal cord-injured athletes. Furthermore, short moderate intensity handbiking but not immediately following long lasting high intensity handbiking further increases serum BDNF concentrations. IGF-1 response to exercise differs to BDNF response as this neuroplasticity-related protein remains elevated during the long lasting physical demand with high intensity. The augmented PRL concentration suggests that a possible mechanism by which exercise promotes neuroplasticity might be the activation of neural serotonergic pathways as 5-HT is the main PRL releasing factor. Elevated COR concentrations after M are unlikely to be deleterious to neuroplasticity as COR concentrations remain within the physiological range. The present study suggests that exercise might be beneficial to enhance neuroprotection and neuroplasticity, thereby improving recovery after spinal cord injury.

Intense exercise increases adenosine concentrations in rat brain: implications for a homeostatic sleep drive.

Intense exercise and sleep deprivation affect the amount of homeostatically regulated slow wave sleep in the subsequent sleep period. Since brain energy metabolism plays a decisive role in the regulation of behavioral states, we determined the concentrations of nucleotides and nucleosides: phosphocreatine, creatine, ATP, ADP, AMP, adenosine, and inosine after moderate and exhaustive treadmill exercise as well as 3 and 5 h of sleep deprivation and sleep in the rat brain using the freeze-clamp technique. High intensity exercise resulted in a significant increase of the sleep-promoting substance adenosine. In contrast, following sleep, inosine and adenosine levels declined considerably, with an accompanied increase of ADP after 3 h and ATP after 5 h. Following 3 h and 5 h sleep deprivation, ADP and ATP did not differ significantly, whereas inosine increased during the 3 and 5-h period. The concentrations of AMP, creatine and phosphocreatine remained unchanged between experimental conditions. The present results are in agreement with findings from other authors and suggest that depletion of cerebral energy stores and accumulation of the sleep promoting substance adenosine after high intensity exercise may play a key role in homeostatic sleep regulation, and that sleep may play an essential role in replenishment of high-energy compounds.

Performance diagnostics in handbiking during competition.

STUDY DESIGN: Case study in handbiking under competition conditions. OBJECTIVE: To investigate exercise-induced, metabolic, pulmonary, cardiovascular and energetic reactions of a paraplegic athlete during a city marathon. SETTING: City marathon Cologne, Germany. SUBJECT: We tested a 27-year-old male athlete from the German national team. The handicap of the athlete was a complete traumatic spinal cord injury ASIA/IMSOP Grade A at the level of the fourth thoratic vertebra (Th4). METHOD: In the competition, the athlete used his own race handbike whose crank system had been exchanged for a power measurement system with registering option. For measuring ventilatory gas parameters during exercise, a portable spirometric system was used. The athlete managed to finish the marathon race in 1:48:54 h. RESULTS: The mean oxygen uptake (VO2) during the marathon was 1580 ml/min, with a maximum value of 2535 ml/min. The mean heart frequency was 137 bpm with a maximum of 157 bpm. During the race the mean energy consumption was 463 kcal/h with a maximum of 758 kcal/h. Prior to the race, the blood lactate value was 2.9 mmol/l; after 10 km 4.4 mmol/l; after 20 km 2.9 mmol/l, and after 30 km 2.9 mmol/l. CONCLUSION: Competition-oriented handbikers should concentrate on exercise units of long duration at low intensities--like marathon runners or cyclists--in order to improve their aerobic performance capacity. However, it has to be pointed out that paraplegic athletes develop relatively high metabolic intensities in competition and that the variability of their physiological parameters is considerably high.

Plasma prolactin concentration increases after hypercapnia acidosis.

Responses of plasma prolactin (PRL) concentration to alterations in carbon dioxide pressure ( pCO(2)) induced by 4 min of rebreathing out of a bag with 6 l gas initially containing a concentration of 93% O(2) and 7% CO(2) (hypercapnia hyperoxia; HH) and 4 min of voluntary hyperventilation (VH) at a respiratory rate of 28 - 32 per minute were investigated in ten males. During rebreathing in HH, an augmentation of pCO(2) from 40.2 +/- 2.1 to 63.7 +/- 5.4 mmHg and a decrease of pH from 7.4 +/- 0.02 to 7.32 +/- 0.04 were found in capillary blood (p < 0.01). Neither breathing frequency (BF) nor plasma PRL changed during this period. After two minutes of post-rebreathing, pCO(2) and pH returned to basal values. BF increased from 2 min of rebreathing (12.4 +/- 1.9 breath/min) until 11 min of recovery period (18.1 +/- 4.9 breath/min) (p < 0.01), while plasma PRL increased from end of rebreathing (11.59 +/- 1.49 ng/dl) to 11 min of recovery period (13.63 +/- 1.97 ng/dl) (p < 0.01). In VH, hyperventilation decreased pCO (2) from 39.91 +/- 2.62 to 21.73 +/- 2.59 mmHg (p < 0.01) and increased pH from 7.39 +/- 0.04 to 7.58 +/- 0.04 (p < 0.01) in capillary blood. After four minutes of recovery from hyperventilation, pH and pCO(2) were back to their basal values. No changes in plasma PRL were found throughout VH. This present pilot study's new finding is that plasma PRL increases after hypercapnia acidosis. This indicates that acidosis-induced central chemoreflex function increases phrenic nerve activity based on serotonergic modulation, leading to an augmentation of BF. As serotonin is also the main PRL-releasing factor, this might have had the collateral effect of causing PRL release and delayed appearance in the peripheral circulation.

Physiology and pathophysiology of the serotonergic system and its implications on mental and physical performance. Part I.

Serotonin (5-HT), one of the evolutionary oldest central neurotransmitters, regulates the most extensive modulatory behavioral system in the brain of vertebrates. 5-HT projections are influenced by extrinsic and intrinsic impulses from different cortical brain areas, which reach Raphe nuclei over feedback loops, containing external and internal body information about planning, evaluation, motivation or excitation. Serotonergic neurotransmission adjusts neuromodulation with consecutive adequate stimulation of the neuronal network. This depends on appropriate equilibration of presynaptic 5-HT storage and release but also on 5-HT reuptake from synaptic cleft by 5-HT transporters. The associated pre and postsynaptic 5-HT receptor cooperation, postsynaptic second messenger response and phosphoinositide signaling mediated by postsynaptic 5-HT(2) receptor subpopulation alter signal transduction in which myristolated alanine rich C kinase substrate is prominently involved in regulation of further central 5-HT areas in the brain and corresponding functional neuronal changes. Even though the central function of 5-HT neurotransmission is dominating in the multifold behavioral regulation, peripheral concentration of tryptophan (TRP) adjusted by hepatic and non-hepatic TRP pyrrolase, TRP liberation from albumin especially by adrenergic stimulation of free fatty acids, TRP passage across the blood-brain barrier and TRP hydroxylase activity are also important for appropriate 5-HT neurotransmission as they affect central 5-HT synthesis. The high adaptability of 5-HT neurotransmission is able to compensate neuromodular dysfunctions in the brain by mechanisms which mediate 5-HT biosynthesis, release, reuptake, pre and postsynaptic receptor stimulation with the respective second messenger response and signal transduction to various areas of the brain which are involved in regulation of behavior, mood, memory, learning and attenuation of obsession, depending on the different vigilance states of the subject. Adequate 5-HT system function supports regulation of intercommunicative neuronal transmission in the brain, which optimizes behavioral neuromodulation during and after transient disturbances of neuromodular behavior caused by stress-induced exertions, but also in permanent disorder such as major depression. Serotonergic neurotransmission improves the clinical course due to compensatory 5-HT impulse correction. This hypothetical interpretation of the serotonergic central neuromodular regulation and interaction with the neuronal network is supported by findings both in functional disturbances and persistent impairments in mental disorders. A comparison of the symptomatology in permanent and transient disturbance of brain neuromodulation enhances our basic knowledge on the regulative factors e. g. in endogenous depression and depressive behavioral changes after exhaustive exercise. This consideration exhibits that the interaction between altered central neuromodulation and peripheral metabolic and hormonal dysfunctions is able to differentiate the etiology of the symptoms. It is suggested that the central neuromodular disturbance of stress-induced causes might initiate the manifestation of the impairment. The theoretical background of this hypothesis is discussed in the present review.