Event Abstract Back to Event Effects of microgravity on characteristics of the accuracy control of movements Tatiana A. Shigueva1*, Vladimir V. Kitov1, Lyubove E. Amirova1, Roman N. Chuprov-Netochin2, Elena S. Tomilovskaya1 and Inessa B. Kozlovskaya1 1 Institute of Biomedical Problems (RAS), Russia 2 Moscow Institute of Physics and Technology, Russia INTRODUCTION Results of previous studies have shown that hypogravitational motor syndrome is characterized by alterations in all components of the motor system (Kozlovskaya et al., 1987; Reschke et al., 1998). Motor control disturbances, such as kinematics changes of locomotion and the decline of postural stability are constantly registered after exposure to weightlessness or simulated microgravity (Gurfinkel et al., 1969; Kozlovskaya et al., 1981). These changes are caused by the development of a number of negative motor disturbances such as decrease of muscle tone and maximal voluntary contraction force (Kakurin et al., 1971; Berry, 1973; Grigoriev et al, 2004), decline of accuracy of muscle contraction forces control, increase of motor task execution time and others (Chkhaidze, 1968; Chekirda et al., 1974; Kozlovskaya et al., 2003). These alterations form a hypogravitational ataxia syndrome (Grigoriev et al, 2004). Support withdrawal is one of important factors of weightlessness. According to the results obtained in IBMP RAS researches most of motor effects of microgravity are fully reproduced on Earth under conditions of Dry Immersion (DI), which seems to be one of the most adequate ground simulation model of weightlessness (Shulzhenko and Vil-Villiams, 1975; Kozlovskaya et al., 1988; Tomilovskaya et al, 2013). The goal of the present work was to study effects of support withdrawal on precision characteristics of programmed movements. METHODS The studies were carried out with participation of 20 healthy male volunteers that were exposed to Dry Immersion (DI). Twelve of them experienced DI for 5 days, eight others – for 7 days. To obtain precise voluntary movements characteristics a force gradation task with single-joint isometric plantar flexions has been used. During the task a subject performed a number of efforts - from the minimal to the maximal one with the minimal difference between neighboring movements. The initial minimal effort that is considered as an absolute threshold of the precision control system and the mean difference between neighboring efforts – considered as a differential threshold - were analyzed. The cases in which the subsequent effort didn't exceed the previous one were defined as an error. The number of properly executed efforts and errors were also analyzed. The aim of the second part of the study was to analyze the recruitment order of spinal motor neurons participating in execution of the task. While executing the second task a subject maintained a small muscle effort (up to 7% from maximal voluntary contraction). During the task the motor units (MU) activities of the leg extensors (m. soleus and m. gastrocnemius lateral) were recorded using sterile needle concentric electrodes. The number of MU displayed on the screen under these conditions didn't exceed 4 or 5. Peak amplitude and duration of interspike intervals (ISI) were analysed. Experiments were performed before DI, twice in the course of DI and on the next day after its completion. The Wilcoxon nonparametric criteria was used for statistical data analysis. RESULTS AND DISCUSSION Under conditions of simulated microgravity the motor task was executed as usual correctly. However more precise analysis of the data has revealed a decrease of leg movement control system accuracy expressed by a decrease of the number of distinguished efforts and an increase of the differential thresholds. The number of gradations decreased significantly (р<0,05) to 29,5 ±14,3 on day 5 of immersion (versus 36,5±13,8 in base data collection) (Figure 1A). The value of differential threshold of effort increased significantly (р<0,05) up to 4,5 ±1,5 (versus 5,7±1,7 in base data collection) on day 5 of immersion (Figure 1B). Figure 1. (A) The number of gradations. (B) The values of the differential threshold of effort. DI5 – 5th day of DI, BDC – base data collection. * – significant changes in comparison to BDC, p<0,05. Motor unit recruitment order in the task of small isometric effort was assessed by the frequency characteristics of MU in the course of 7-day dry immersion experiment. In full accordance with previous data (Sugajima et al., 1996; Kozlovskaya and Kirenskaya, 1986, 2004) small plantar flexion effort (0-5,5% of maximal voluntary contraction of about 140 kg) before exposure to DI was provided by the activity of small motoneurons. The number of MU involved in the task execution averaged 68,6% (of total number) in m. soleus (Figure 2A) and 77,3% – in m. gastrocnemius lat. (Figure 2B); the average interspike intervals (ISI) were in the range of 100-160 ms. The order of MU involvement in both muscles under DI conditions changed significantly. MUs with ISIs of 100-130 ms were not registered at all during the task execution on the 3d day of DI. The most of MUs involved had ISIs of 160-200 ms. Only 59.3% of MU with ISI in the range of 130-160 ms were involved in the task execution in m. soleus (Figure 2A), and 28% – in m. gastrocnemius lat. (Figure 2B). Increase of ISI values in case of constant low-level isometric effort maintenance shows that the small effort under microgravity conditions is provided by the larger MUs. The altered order of MUs involvement remained also on the 7th day of DI and even after its completion. Thus, our studies have shown a decrease of precision in programmed movements under conditions of immersion which is caused not only by changes in cortical programming mechanisms (Kozlovskaya and Kirenskaya, 2004), but also by recruitment order alterations in motor neuron pool (violation of Henneman law) (Henneman et al., 1965) which decreases its ability to control precisely movements of low contraction level due to inactivity of small (postural) motor units. Figure 2. Histogram of the distribution of MU by ISI in m. soleus and m. gastrocnemius lat. (А) before DI; (B) in the course of DI; BDC – base data collection, DI3 – 3d day of DI, DI7 – 7th day of DI. CONCLUSIONS Exposure to support withdrawal conditions is followed by a decrease of precision in muscle force control. Results of motor neuron recruitment order study showed that disturbances in precise movement control is caused not only by changes in programming mechanisms but also by changes in recruitment order of small motor neurons responsible for execution of low-level contractions. Figure 1 Figure 2 Acknowledgements The study is supported by RFBR project 18-315-00287. References 1. Berry, C.A. (1973) View of human problems to be addressed for long-duration space flights. Aerospace Medicine. 44, 1136-1146. 2. Chekirda, I.F., and Eremin, A.V. (1974) Dynamics of cyclic and acyclic locomotion by the crew of "Soyuz-18" after a 63-day space flight. Kosm Biol Aviakosm Med. 11:4, 9-13. 3. Chkhaidze, L.V. (1968) Coordination of voluntary movements of man in spaceflight environment. Nauka, Moscow, 133. 4. Grigoriev, A.I., Kozlovskaya, I.B., and Shenkman, B.S. (2004). 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Studies in real and simulated weightlessness», in: Stance and Motion, eds. V.S. Gurfinkel, M.Ye. Ioffe., J. Massion, J.P. Roll. (Plenum. New York), 37-48. doi: 10.1007/978-1-4899-0821-6_4 10. Kozlovskaya, I.B., and Kirenskaya, A.V. (2003). Mechanisms of impairment of precise movements during long-term hypokinesia. Rossiyskiy fiziologicheskiy zhurnal imeni I.M. Sechenova. 89, 247-58. 11. Kozlovskaya, I.B., and Kirenskaya, A.V. (2004). Mechanisms of Disorders of the Characteristics of Fine Movements in Long-Term Hypokinesia. Neuroscience and behavioral physiology. 34. 747-54. doi: 10.1023/B:NEAB.0000036017.46801.5c. 12. Kozlovskaya, I.B., Aslanova, I.F., and Kirenskaya, A.V. (1987) «The Effect of Support Unloading on Characteristics of Motor Control Systems Activity», in Motor Control, ed. Gantchev, G.N., Dimitrov, B., Gatev, P. (Springer, Boston, MA), 149-152. doi: 10.1007/978-1-4615-7508-5_26. 13. Kozlovskaya, I.B., Kreidich, Yu.V., Oganov, V.S., and Koserenko, O.P. (1981) Pathophysiology of motor functions in prolonged manned space flights, Acta Astronautica, 8:9–10, 1059-1072, https://doi.org/10.1016/0094-5765(81)90079-5. 14. Reschke, M.F., Bloomberg, J.J., Harm, D.L., Paloski, W.H., Layne, C., McDonald, V. (1998) Posture, locomotion, spatial orientation, and motion sickness as a function of space flight. Brain Research Reviews. 28:1–2, 102-117. doi: 10.1016/S0165-0173(98)00031-9. 15. Shulzhenko, E.B., and Vill-Villiams, I.F. (1975). Simulation of the human body deconditioning with the method of «Dry» Immersion. Moscow: X reading K.E. Tsiolkovsky, 39-47 16. Sugajima, Y., Mitarai, G., Koeda, M., and Moritani T. (1996) Characteristic changes of motor unit activity in hip joint flexor muscles during voluntary isometric contraction during water immersion. J Electromyogr Kinesiol. 6:2, 83-95. doi: 10.1016/1050-6411(95)00020-8. 17. Tomilovskaya, E.S. (2013). Experiment with five-day dry immersion: objectives, content, structure of the investigations, and specific methods. Human Physiology, 39:7, 756-761. Keywords: dry immersion, Motor unit (MU), hypogravitational motor syndrome, support unloading, microgravity, motor control Conference: 39th ISGP Meeting & ESA Life Sciences Meeting, Noordwijk, Netherlands, 18 Jun - 22 Jun, 2018. Presentation Type: Extended abstract Topic: Neurosciences and psychology Citation: Shigueva TA, Kitov VV, Amirova LE, Chuprov-Netochin RN, Tomilovskaya ES and Kozlovskaya IB (2019). Effects of microgravity on characteristics of the accuracy control of movements. Front. Physiol. Conference Abstract: 39th ISGP Meeting & ESA Life Sciences Meeting. doi: 10.3389/conf.fphys.2018.26.00051 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers' terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 02 Dec 2018; Published Online: 16 Jan 2019. * Correspondence: Ms. Tatiana A Shigueva, Institute of Biomedical Problems (RAS), Moscow, Moscow Oblast, Russia, t.shigueva@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Tatiana A Shigueva Vladimir V Kitov Lyubove E Amirova Roman N Chuprov-Netochin Elena S Tomilovskaya Inessa B Kozlovskaya Google Tatiana A Shigueva Vladimir V Kitov Lyubove E Amirova Roman N Chuprov-Netochin Elena S Tomilovskaya Inessa B Kozlovskaya Google Scholar Tatiana A Shigueva Vladimir V Kitov Lyubove E Amirova Roman N Chuprov-Netochin Elena S Tomilovskaya Inessa B Kozlovskaya PubMed Tatiana A Shigueva Vladimir V Kitov Lyubove E Amirova Roman N Chuprov-Netochin Elena S Tomilovskaya Inessa B Kozlovskaya Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.
Radioresistance compromises the efficacy of radiotherapy for glioblastoma multiforme (GBM), the most devastating and common brain tumor. The present study investigated the relationship between radiation tolerance and formation of polyploid/multinucleated giant (PGCC/MGCC) and quiescent/senescent slow-cycling cancer cells in human U-87, LN-229, and U-251 cell lines differing in TP53/PTEN status and radioresistance. We found significant enrichment in MGCC populations of U-87 and LN-229 cell lines, and generation of numerous small mononuclear (called Raju cells, or RJ cells) U-87-derived cells that eventually form cell colonies, in a process termed neosis, in response to X-ray irradiation (IR) at single acute therapeutic doses of 2-6 Gy. For the first time, single-cell high-content imaging and analysis of Ki-67- and EdU-coupled fluorescence demonstrated that the IR exposure dose-dependently augments two distinct GBM cell populations. Bifurcation of Ki-67 staining suggests fast-cycling and slow-cycling populations with a normal-sized nuclear area, and with an enlarged nuclear area, including one resembling the size of PGCC/MGCCs, that likely underlie the highest radioresistance and propensity for repopulation of U-87 cells. Proliferative activity and anchorage-independent survival of GBM cell lines seem to be related to neosis, low level of apoptosis, fraction of prematurely stress-induced senescent MGCCs, and the expression of p63 and p73, members of p53 family transcription factors, but not to the mutant p53. Collectively, our data support the importance of the TP53wt/PTENmut genotype for the maintenance of cycling radioresistant U-87 cells to produce a significant amount of senescent MGCCs as an IR stress-induced adaptation response to therapeutic irradiation doses.
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