Contractile characteristics of the triceps surae muscle in healthy males during 120-days head-down tilt (HDT) and countermeasures

To reveal mechanisms responsible for changes in muscle contractility during microgravity, it seems expedient to perform similar studies under microgravity or conditions simulating microgravity. Among standard methods for simulating microgravity, hypokinesia modelling support unloading (or rather its redistribution), and hypodynamia are employed. Absence of weight loading, decreased muscular effort characteristic of the Earth conditions due to counteracting gravity, results in a general muscle underloading and therefore in lowered activity of the proprioceptive input. This may be one of the reasons not only for a resetting of motor coordination and control, but also for a gradual development of a persistent change in the motor control system. The basis of countermeasures against negative consequences of microgravity (hypokinesia) is the correct choice of countermeasures. In this connection of specific interest is a study of the magnitude of change in skeletal muscle contractility in humans after a variety of countermeasures when functional activity is lowered by a long-term 120-days HDT which is an adequate simulation of physiological microgravity-induced effects.     

Human muscle atrophy in supportlessness: effects of short-term exposure to dry immersion

Atrophy of skeletal muscle is a response that is considered as the most consistent under conditions of real and simulated weightlessness. Microgravity is transformed in the motor system into a number of factors, the most important of them are considered axial unloading and support unloading. The effects of support stimulus may be evaluated in studies under conditions of dry immersion (DI) which provides the equal distribution of the mechanical pressure (e.g. hydrostatic pressure) throughout the surface of the body. Thus the deprivation of the gradient of the mechanical pressure simulates the supportless conditions. The study was aimed to test if the support unloading simulated in dry immersion induces not only functional but also structural alterations in human postural muscles.     

Adaptation of the Human Body to Simulated Weightlessness: Clinical Studies

Problems of adaptation of functional systems of the human body to conditions of continuous weightlessness are considered (prolonged stay under conditions of antiorthostatic hypokinesia and in an immersion medium). It was revealed that, during adaptation to these conditions, polymorphic clinicofunctional disorders develop, transforming into clinicophysiological syndromes, the most frequently observed being autonomic vascular malfunction, asthenoneurotic syndrome, detraining of the blood circulatory system, trophic and neuromuscular disorders, statokinetic syndrome, pain syndrome, and metabolic and hormonal disorders. The severity of the specified disorders and the duration of the recovery period depend on the duration of hypokinesia and the intensity and regularity of application of preventive measures during hypokinesia. The most probable pathophysiological mechanisms of adverse effects of continuous hypokinesia (maladaptation) on functional systems of the human body are described.     

Myelination disorders in the mechanism of hypogravity motor syndrome development

When modeling the effects of hypogravity by the method of hindlimb unloading in rats, the area of cross-section in the lumbar part of spinal cord was found to reduce. Analysis of spinal cord slides showed that these changes are associated with a decrease in the area of white substance. The data obtained are consistent with our previous observation of a decrease in expression of the genes encoding myelin proteins. The results of our research give good reasons to believe that myelination failure in CNS is one of the factors that underlie the development of the hypogravity motor syndrome.     

Structure-activity relationships of 18 endogenous neuropeptides on the motor nervous system of the nematode Ascaris suum

Neuropeptides play an important role in all nervous systems and structure-activity studies of related peptides is one approach to understanding this role. This study of the motor nervous system of the parasitic nematode Ascaris suum describes the physiological effects of a family of 18 endogenous Ascaris FMRFamide-like peptides (AF peptides) on the membrane potential and input resistance of the dorsal excitatory type 2 (DE2) and dorsal inhibitory (DI) motor neurons. These motor neurons are part of the final common output pathway from the motor nervous system to the somatic muscle cells responsible for locomotion. AF peptide effects on the frequency of excitatory postsynaptic potentials (EPSPs) in DE2 motor neurons were also measured to infer peptide effects on central presynaptic spiking neurons. AF peptide injections into intact worms were made to assess their qualitative effects on behavior, providing a context for interpreting motor neuron data. One category of AF peptides, N-terminally extended -FIRFa peptides (AF5, AF7 and AF1), has pronounced behavioral effects and qualitatively similar, but quantitatively different effects on DE2 and DI motor neurons. A second category of AF peptides (AF2, AF9, and AF8) also produces dramatic behavioral effects and strong electrophysiological effects on DE2 and/or DI motor neurons. A third category of AF peptides, consisting of six members of the -PGVLRFa group (which are encoded by the same gene and have closely related sequences) and peptide AF11, have pronounced behavioral effects, but relatively weak or negligible effects on DE2 and DI motor neurons. A fourth category of AF peptides, also consisting of structurally unrelated members, has pronounced behavioral effects and, as individual peptides, similar effects on both DE2 and DI motor neurons; AF15 is excitatory, while AF17 and AF19 are inhibitory, on both motor neuron types. Finally, two AF peptides (AF6, AF16) are relatively weak or inactive in producing behavioral or motor neuronal effects. Based on comparisons of the effects of AF peptides on DE2 and DI motor neurons, a tentative list of 5 major response-types is proposed as a working hypothesis to guide the search for AF peptide receptors. The findings attest to the potential complexity of neurosignaling in this comparatively simple nervous system.     

Effects of gravitational unloading on back muscles tone

The study involved 12 healthy volunteers who were exposed to 6-h or 3-day dry immersion (DI). The back muscle tone was recorded by resonance vibrography using parameters of transverse stiffness of the muscles under study. The measurements in 3-day DI were performed twice before DI, daily in the course of DI, and twice after its completion; in the short-term (6-h) DI, the testing was carried out twice before DI, 1 and 4 h after the beginning of DI, and during the first hour after DI completion. It has been shown that the absence of support is followed by a sharp decrease in the back extensor muscles tone, which has the maximal values during the first hours and days of DI. The possible role of back muscle atony in the development of well-known phenomena of the spine length increase and back pain appearance observed at the beginning of space flights and in the first days after landing, as well as under the conditions of simulated microgravity (DI and head-down bed rest), is discussed.     

Recent physiological and pathophysiological aspects of Parkinsonian movement disorders

Deficits in the neural control of limb movements constitute a major part of Parkinsonian symptoms and are linked to a decay of dopaminergic neurotransmission. In animal models, Parkinsonian-like hypokinesia is consistently reproduced with large nigrostriatal dopamine depletions, while tremor and rigidity are less readily obtained. Lesions leading to a less than 70% striatal dopamine depletion are largely compensated by an increased activity of dopamine terminals. With more important lesions, supersensitivity of striatal non-adenylate cyclase-linked dopamine receptors occurs. Electrophysiological studies in Parkinsonian patients demonstrate increased reaction times and a reduced build-up of movement-related muscular activity underlying hypokinesia and provide circumstantial evidence for a central origin of tremor and rigidity. Single cell activity in unlesioned, behaving monkeys shows an increasingly direct relationship to movements when following the neural connections from mid-brain dopamine cells via striatum, globus pallidus, thalamus to pyramidal tract neurons of motor cortex. These data corroborate experimentally the concept that Parkinsonian hypokinesia is due to a failure of basic behavioral activating mechanisms.     

Effects of support stimulation on human soleus fiber characteristics during exposure to "dry" immersion

In this study the model of 7-day dry immersion (DI) was used. 17 male volunteers (23-29 years old) were divided in 2 groups: (i) 7-day DI without support (DI, n=9), (ii) 7-day DI using support stimulation (DIS, n=8). Support stimulator device exerted pressure of 0.2 +/- 0.15 kg/cm2 upon the plantar support zones simulating the walking pattern 6 times a day for 20 minutes of every hour: 10 minutes at a speed of 75 steps/min and 10 minutes at a speed of 120 steps/min. M. soleus biopsy was performed before and immediately after DI. The m. soleus fiber myosin heavy chain (MHC) profile, myofiber cross-sectional area (CSA) and total protein concentration were analyzed in frozen serial sections. In addition, NO-synthase 1 (NOS1) levels indicative of normal muscle cell signaling were analyzed by western blotting in 4 persons in each group. After dry immersion, percentage of muscle fibers containing type I MHC decreased by 6% (p<0.05) in group DI, but was not changed significantly in group DIS. Percentage of the type IIa fibers was significantly altered in none of the groups. Type I fiber CSA decreased by 24.4% (p<0.05) in group DI. No significant changes of type I fiber CSA were found in group DIS. CSA of the type IIa fibers significantly altered in none of the groups. The total protein concentration was found increased by 17.6% in group DI and by 21% in group DIS. The increased total protein content in group DI suggests a diminution of fiber CSA attributed to the loss of non-protein component of fibers. NOS1 decreased by 35.6% in group DI and increased by 58.1% in group DIS. We conclude that 7 days in dry immersion lead to reduction in the type I muscle fiber percentage, loss of the non-protein component and decline in NOS1. These changes were clearly prevented by the support stimulation protocol applied during the DI period.     

Analysis of the interdependence of temperament, neuroendocrine control, and psychophysiological state during dry immersion

The interdependence of temperament and the hormonal and psychophysiological states was investigated in eight young volunteers during seven-day dry immersion (DI). The levels of insulin and sex, steroid, and thyroid hormones in the blood and the psychomotor parameters were determined on days 3 and 7 of DI and on day 7 of recovery. Before DI, the volunteers filled in Cattell’s personality questionnaire. During DI, anxious subjects spent less time to compare visual patterns, demonstrating a stably high speed of reactions with a slight quality loss. Extraverts showed a high speed of reactions and stability of psychomotor parameters without an increase in the number of errors. Easy-tempered and introvert subjects retained inherently high insulin concentrations in DI. Support deprivation was accompanied by the drop of the triiodothyronine and cortisol levels and an increase in prolactin and thyroxin. The results of multiple correlation analysis led to the conclusion that DI emphasizes the role of original extra-introversion and dampers the original anxiety. Success can be attained by adequate alteration of the levels of steroid and thyroid hormones with effectively balanced vagoinsulin—sympathoadrenal neuroendocrine control and monoaminergic CNS activity.     

Bronchoprotective and bronchodilatory effects of deep inspiration in rabbits subjected to bronchial challenge.

The effect of deep inspiration (DI) on airway responsiveness differs in asthmatic and normal human subjects. The mechanism for the effects of DI on airway responsiveness in vivo has not been identified. To elucidate potential mechanisms, we compared the effects of DI imposed before or during induced bronchoconstriction on the airway response to methacholine (MCh) in rabbits. The changes in airway resistance in response to intravenous MCh were continuously monitored. DI depressed the maximum response to MCh when imposed before or during the MCh challenge; however, the inhibitory effect of DI was greater when imposed during bronchoconstriction. Because immature rabbits have greater airway reactivity than mature rabbits, we compared the effects of DI on their airway responses. No differences were observed. Our results suggest that the mechanisms by which DI inhibits airway responsiveness do not depend on prior activation of airway smooth muscle (ASM). These results are consistent with the possibility that reorganization of the contractile apparatus caused by stretch of ASM during DI contributes to depression of the airway response.     

Visual-manual tracking and vestibular function during a seven-day dry immersion

A seven-day dry immersion experiment provided the opportunity to study the effects of decreased proprioceptive tactile and support afferentations on the vestibular function and visual-manual tracking. Before and after immersion, six subjects participated in a video oculographic evaluation of the static torsion otolith-cervicoocular reflex (OCOR) in response to head tilt by 30° in the frontal plane and dynamic vestibular-cervicoocular reactions to head longitudinal rotations at 0.125 Hz. In addition, the hand-eye motor coordination of tracking a jerky (sinusoidal) or smooth (linear) movement of point targets along the horizontal or vertical lines was evaluated on the basis of the data of electrooculography and records of manipulations with the joystick during immersion. A computerized test was performed in virtual glasses displaying images of visual stimuli and hand motor acts. The computed parameters included the reaction’s latent time, amplitude, speed and time of eye and hand movements, and gains of optooculomotor reactions and manual tracking as a ratio of eye/hand to visual stimulus speed. Testing was carried out before the experiment, after 3 h of immersion, on days 3 and 6 of staying in the bath, in the initial hours after immersion and on the third day of recovery. It was shown that removal of support and minimization of proprioceptive afferentation had a profound effect on the ocular tracking rather than pursuing the visual stimulus by hand. The accuracy of manual tracking was better in comparison with the eye tracking in all subjects. This was the first observation of changes in the peripheral vestibular system in two out of six subjects, i.e., inversion of the static torsion OCOP and positional nystagmus against a background of converted reflex, which did not change the parameters of the visual-manual tracking.     

Models to study gravitational biology of Mammalian reproduction

Mammalian reproduction evolved within Earth's 1-g gravitational field. As we move closer to the reality of space habitation, there is growing scientific interest in how different gravitational states influence reproduction in mammals. Habitation of space and extended spaceflight missions require prolonged exposure to decreased gravity (hypogravity, i.e., weightlessness). Lift-off and re-entry of the spacecraft are associated with exposure to increased gravity (hypergravity). Existing data suggest that spaceflight is associated with a constellation of changes in reproductive physiology and function. However, limited spaceflight opportunities and confounding effects of various nongravitational factors associated with spaceflight (i.e., radiation, stress) have led to the development of ground-based models for studying the effects of altered gravity on biological systems. Human bed rest and rodent hindlimb unloading paradigms are used to study exposure to hypogravity. Centrifugation is used to study hypergravity. Here, we review the results of spaceflight and ground-based models of altered gravity on reproductive physiology. Studies utilizing ground-based models that simulate hyper- and hypogravity have produced reproductive results similar to those obtained from spaceflight and are contributing new information on biological responses across the gravity continuum, thereby confirming the appropriateness of these models for studying reproductive responses to altered gravity and the underlying mechanisms of these responses. Together, these unique tools are yielding new insights into the gravitational biology of reproduction in mammals.     

The effect of head-down hypokinesia on functional state of diaphragm in rats

The effects of long-term (21 days) head-down (-30 degrees) hypokinesia (HDH) on respiratory system and a functional state of diaphragm were investigated in rats. Minute ventilation, oesophageal and abdominal pressure, integrated electrical activity of diaphragm were measured in control and experimental group (after 21 days of HDH) of animals. The measurements were made in several body positions atresting and in occlusion breathing. The results indicate that HDH causes reduction in minute ventilation of lungs, decrease in orthostatic stability and functional reserve of the respiratory system capacity. It was established that the basic mechanism of HDH respiratory effects is contractile failure of diaphragm related to damage in excitation-contraction coupling in its muscular fibres.     

Dynamics of oxidation stress markers during long-term antiorthostatic hypokinesia: A retrospective study

Nine volunteers aged 27 to 42 participated in an experiment with 370-day antiorthostatic hypokinesia at–5°C, and their blood serum samples were tested for the concentrations of lipid peroxidation (LPO) derivatives, including diene conjugates (DCs), malonic dialdehyde (MDA), and Schiff bases (SBs), and indices of the antioxidant defense system, including the tocopherol (TP) concentration and total antioxidant activity (AOA). The subjects were divided into two groups, which differed in physical training regimen and prophylaxis measures. Initial LPO steps were inhibited in both of the groups by 54–73% from day 50, while the level of SBs, which are final LPO products, decreased by 50–61% by day 230 and remained much the same up to the end of the experiment. The MDA and SB concentrations decreased by a factor of 1.6–2.3 during recovery. Total AOA decreased as an aftereffect during recovery to a level far lower than physiologically normal. Based on the significant inhibition of free-radical LPO throughout the experiment, long-term adaptation to simulated hypogravity was accompanied by a pronounced decrease in biological oxidation and caused severe stress. Substantial long-term readaptation stress developed during recovery after 370-day antiorthostatic hypokinesia, as was evident from the facts that the LPO activity was almost halved, TP concentration significantly increased, and the functional reserves of water-soluble antioxidants were exhausted. Lack of LPO activation was assumed to reflect adequate compensation in the subjects.     

Perinatal model of human transition from hypogravity to Earth’s gravity based on nonlinear electromyogram characteristics

Interferential electromyogram (iEMG) was analyzed in healthy newborns (n = 29) during the first 24 h of life as a model of transition from hypogravity (intrauterine immersion) to Earth’s gravity (the postnatal period). Nonlinear methods of iEMG analysis (correlation dimension, entropy, and fractal dimension) reflecting the complexity, chaotic character, and predictability of signals from the leg and arm antagonistic muscles were used. The iEMG fractal dimension was shown to grow in all the muscles as the postnatal period extended, except the m. gastrocnemius during the first 24 h of life. Lower fractal and correlation dimensions and entropy were found to be characteristic of the flexors, especially at a low iEMG amplitude suggesting better congenital programming of the flexors compared to the extensors. It was concluded that the early ontogenesis model can be potentially useful for studying the evolution and the states of antigravity functions.     

Expression of cell adhesion molecules and lymphocyte-endothelium interaction under simulated hypogravity in vitro

Using histochemical staining and FACS-analysis we have studied the basal and TNF-alpha induced expression of E-selectin, ICAM-1 and VCAM-1 in human umbilical vein endothelial cells (ECs) exposed to simulated hypogravity. Control ECs did not contain detectable amounts of E-selectin or VCAM-1 but were ICAM-1 positive. As soon as after 6-8 hrs of clinorotation at 5 RPM the cellular content of ICAM- 1 increased. Moreover, hypogravity potentiated the effect of inflammatory cytokines (TNF-alpha and IL-1) on ICAM-1 expression. No increase in E-selectin or VCAM-1 expression was observed in ECs exposed to hypogravity itself. However, hypogravity reduced E-selectin and VCAM-1 expression in cell cultures activated by cytokines, more visible at their low (5-10 U/ml) concentrations. Both, control and clinorotated ECs poorly supported spontaneous lymphocyte adhesion; the adhesion of PMA-activated leukocytes was 15-20-fold higher. The interaction of unstimulated lymphocytes with cytokine-activated endothelium was more noticeable but significantly lower in cultures exposed to hypogravity. Activated blood cells interacted with endothelium more effectively, particularly, under hypogravity. Obtained results suggest that EC adhesion molecule expression and endothelium-lymphocyte interaction are altered under simulated hypogravity conditions in direction of increase of endotlielial adhesiveness for activated blood cells.     

Physiological Cost of Physical Exercise and Mitochondrial Volume in Working Muscles of Subjects Exposed to Long-Term Hypokinesia: Effects of Local Resistance Exercise

The results of changes in the physiological cost of 30-min submaximal aerobic bicycle ergometric exercise and characteristics of the mitochondrial apparatus of m. vastus lateralis were assessed comparatively during 120-day (–6°) antiorthostatic hypokinesia either without prophylactic measures or with low-intensity resistance exercise training for 60 days using a Penguin exercise suit. Hypokinesia was accompanied by an increase in the working heart rate and lactate accumulation in the blood during the test exercise, as well as by a decrease in the myofibril size and the volume density of mitochondria in the m. vastus lateralis fibers. The patterns of dynamic changes in the lactate concentration in the blood during exercise training and in the volume density of central mitochondria were found to be similar. A correlation between the rate of lactate accumulation in the blood during the test exercise and the volume density of mitochondria in the working muscle appeared after long-term (60 days) exposure to hypokinesia. The use of the Penguin exercise suit in dynamic mode during prolonged (60-day) exposure to hypokinesia completely prevented the following effects: atrophy of slow-type fibers, a decrease in the volume density of central mitochondria, and an increase in the level of lactate accumulation in the blood under conditions of a standard submaximal aerobic exercise load. The correlation links between the oxidative potential of working muscle and the energy supply of muscular work are discussed.     

Cognitive cost of motor reorganizations associated with muscular fatigue during a repetitive pointing task

Muscular fatigue is known to impair motor performance and to catalyse the development of upper limb musculoskeletal disorders. In order to delay the deleterious effects of muscular fatigue, the central nervous system (CNS) employs compensatory strategies. The cognitive cost of such compensatory strategies was assessed in 10 male subjects who alternatively performed two dual-task protocols before and immediately after an exhaustion procedure specific to upper arm abductor musculature. The main motor tasks were an isometric force-matching and a rapid multi-joint pointing. A secondary probe reaction time (RT) task was performed during both protocols and served as an indicator of attentional demands. Overall motor task performance was maintained despite fatigue. Kinematic and electromyographic data revealed that subjects used motor reorganization during the pointing task when fatigued. The RT increased with fatigue in both dual-task protocols, but this increase was significantly higher during the pointing task than during the force-matching task.The results highlight that the motor reorganization used by the CNS under muscular fatigue states require higher attentional demands than the initial motor organization. Finally, the capacity to delay the deleterious effects of muscular fatigue seems to depend on the proportion of cognitive resources available to plan the compensatory motor strategy.     

Analysis of interdependence of temperament,neuroendocrine control and psychophysiological state during dry immersion

Interdependence of temperament, hormonal and psychophysiological states was investigated in eight young volunteers during seven-day dry immersion (DI). The levels of insulin and sex, steroid, and thyroid hormones in the blood and the psychomotor parameters were determined on days 3 and 7 of DI and on day 7 of recovery. Before DI, the volunteers filled in the Cattell’s Personality Factor Questionnaire. During DI, anxious subjects spent less time to compare visual patterns, demonstrating a high and stable speed of reactions with a slight deterioration. Extraverts showed high speed of reactions and stability of psychomotor parameters without increase in the number of errors. Easy-tempered and introvert subjects preserved inherently high insulin concentrations in DI. Support deprivation was accompanied by the drop of triiodothyronine and cortisol levels and the increase in prolactin and thyroxin. The results of multiple correlation analysis lead to the conclusion that DI increased the role of original extra-introversion and decreased that of the original anxiety. Successful activity can be attained by adequate alteration of the levels of steroid and thyroid hormones with effectively balanced vagoinsular-sympathoadrenal neuroendocrine control and monoaminergic CNS activity.     

Behavioral and neurotrophic activity of ACTH-(7-16)NH2

The behavioral and neurotrophic effects of ACTH-(7-16)NH2 were assessed in a number of tests in which other ACTH fragments are active. Subcutaneous injection of ACTH-(7-16)NH2 increased motor activity of group-housed rats tested under low light intensity and induced hypokinesia in rats subjected to the mild stress of a nonfunctional "hot" plate. In rats with 6-OHDA lesions in the nucleus accumbens daily subcutaneous treatment with ACTH-(7-16)NH2 during the first week following the lesions reversed the lesion-induced motor hypoactivity. The ED50's for the effects of ACTH-(7-16)NH2 on the environmentally induced changes in motor activity, the stress-induced hypokinesia and the impaired motor activity of 6-OHDA lesioned rats were approximately 8 micrograms/kg. 6.3 micrograms/kg and 0.45 micrograms/kg respectively. It is concluded that ACTH-(7-16)NH2 may mimic the effect of an ACTH-like peptide in the brain involved in brain processes triggered by changes in the environment and by brain damage.