Morphological changes in myelinated fibers of the spinal cord and the sciatic nerve in mice after modeling of the hypogravity and the approach of their correction by preventive gene therapy


Cite item

Full Text

Abstract

Earlier, in mice after a 30-day space flight on the Bion-M1 biosatellite, we found signs of a negative effect of weightlessness on the structure of myelinated fibers of the spinal cord tracts; these findings indicate their involvement in the pathogenesis of hypogravitational motor syndrome (HMS). In the present study, under conditions of hypogravity modeling by the hindlimb unloading, we obtained data on destructive changes in the myelinated fibers of the motor posterior corticospinal tract (tractus corticospinalis posterior), sensitive anterior spinocerebellar tract (tractus spino-cerebellaris anterior), and the gracile fascicle (fasciculus gracilis), as well as in the tibial fascicle (fasciculus tibialis) of the sciatic nerve of mice 30 days after unloading. The obtained data confirm our hypothesis on the role of disturbance in the processes of myelination of nerve fibers during the development of HMS, both during space flight and under conditions of simulating hypogravity on Earth. Morphometric analysis after a 7-day period of readaptation did not reveal signs of restoration of pathological changes in myelinated fibers that arose after 30 days of hanging. However, preventive gene therapy (administration of a gene construct providing the synthesis of recombinant vascular endothelial growth factor, glial cell line-derived neurotrophic factor, and neural cell adhesion molecule, prior to hindlimb unloading) has been shown to be effective in the preservation of myelinated fibers in projection anterior spininocerebellar tract, compared with control animals that did not receive gene therapy. The research carried out at this stage gives ground to make a preliminary conclusion about the advisability of developing methods of preventive gene therapy to prevent the development of GDS during long-term space flights.

Full Text

Restricted Access

About the authors

A. N Lisyukov

Kazan State Medical University

Email: artur17@list.ru

M. S Kuznetsov

Kazan State Medical University

V. R Saitov

Kazan (Volga Region] Federal University; Federal State Budgetary Scientific Institution Federal Center for toxicological, radiation, and biological safety

M. M Salnikova

Kazan (Volga Region] Federal University

I. A Bikmullina

Kazan State Medical University

E. S Koshpaeva

Kazan State Medical University

O. V Tyapkina

Kazan State Medical University; Kazan (Volga Region] Federal University

V. V Valiullin

Kazan State Medical University

R. R Islamov

Kazan State Medical University

References

  1. Roy R.R., Zhong H., Bodine S.C. et al. Fiber size and myosin phenotypes of selected rhesus lower limb muscles after a 14-day spaceflight. J. Gravit. Physiol. 2000; 7(1): S45.
  2. Shenkman B.S. From Slow to Fast: Hypogravity-Induced Remodeling of Muscle Fiber Myosin Phenotype. Acta Naturae 2016; 8(4): 47-59.
  3. Comfort P., McMahon J.J., Jones P.A. et al. Effects of Spaceflight on Musculoskeletal Health: A Systematic Review and Meta-analysis, Considerations for Interplanetary Travel, https://link.springer.com/article/10.1007/s40279-021-01496-9.
  4. Fitts R.H., Riley D.R., Widrick J.J. Functional and structural adaptations of skeletal muscle to microgravity. J. Exp. Biol. 2001; 204(18): 3201-8.
  5. Narici M., Kayser B., Barattini P. et al. Effects of 17-day spaceflight on electrically evoked torque and cross-sectional area of the human triceps surae. Eur. J. Appl. Physiol. 2003; 90(3-4): 275-82.
  6. Tesch P.A., Berg H.E., Bring D. et al. Effects of 17-day spaceflight on knee extensor muscle function and size. Eur. J. Appl. Physiol. 2005; 93(4): 463-8.
  7. Rittweger J., Albracht K., Fluck M. et al. Sarcolab pilot study into skeletal muscle’s adaptation to long-term spaceflight. NPJ Microgravity 2018; 4: 18.
  8. Islamov R.R., Tiapkina O.V., Nikolsky E.E. et al. The Role of Spinal Cord Motoneurons in the Mechanisms of Development of Low-Gravity Motor Syndrome. Neuroscience and Behavioral Physiology 2015; 45(1): 96-103.
  9. Chevrel G., Hohlfeld R., Sendtner M. The role of neurotrophins in muscle under physiological and pathological conditions. Muscle Nerve 2006; 33(4): 462-76.
  10. Sakuma K., Yamaguchi A. The recent understanding of the neuro-trophin’s role in skeletal muscle adaptation. J. Biomed. Biotechnol. 2011; 2011: 201696.
  11. Delbono O. Neural control of aging skeletal muscle. Aging Cell 2003; 2(1): 21-9.
  12. Исламов Р.Р., Валиуллин В.В. Нервная регуляция пластичности скелетной мышцы. Неврологический вестник им. В.М. Бехтерева 2014; XLVI(3): 56-64.
  13. Hester M., Foust K., Kaspar R. et al. AAV as a Gene Transfer Vector for the Treatment of Neurological Disorders: Novel Treatment Thoughts for ALS. Current gene therapy 2009; 9: 428-33.
  14. Lim S.T., Airavaara M., Harvey B.K. Viral vectors for neurotrophic factor delivery: A gene therapy approach for neurodegenerative diseases of the CNS. Pharmacological Research 2010; 61(1): 14-26.
  15. Ismailov S.M., Barykova I.A., Shmarov M.M. et al. Experimental approach to the gene therapy of motor neuron disease with the use of genes hypoxia-inducible factors. Genetika 2014; 50(5): 591-601.
  16. Krakora D., Mulcrone P., Meyer M. et al. Synergistic effects of GDNF and VEGF on lifespan and disease progression in a familial ALS rat model. Mol. Ther. 2013; 21(8): 1602-10.
  17. Morey-Holton E.R., Globus R.K. Hindlimb unloading rodent model: technical aspects. J. Appl. Physiol. (1985) 2002; 92(4): 1367-77.
  18. Андреев-Андриевский А.А., Шенкман Б.С., Попова А.С. и соавт. Экспериментальные исследования на мышах по программе полета биоспутника «Бион-М1». Авиакосмическая и Экологическая Медицина 2014; 48(1): 14-27.
  19. Islamov R.R., Rizvanov A.A., Fedotova V.Y. et al. Tandem Delivery of Multiple Therapeutic Genes Using Umbilical Cord Blood Cells Improves Symptomatic Outcomes in ALS. Mol. Neurobiol. 2017; 54(6): 4756-63
  20. Kuznetsov M.S., Lisyukov A.N., Rizvanov A.A. et al. Bioinformatic Study of Transcriptome Changes in the Mice Lumbar Spinal Cord After the 30-Day Spaceflight and Subsequent 7-Day Readaptation on Earth: New Insights Into Molecular Mechanisms of the Hypogravity Motor Syndrome. Front. Pharmacol. 2019; 10: 747.
  21. Лисюков А.Н., Измайлов А.А., Кузнецов М.С. и соавт. Нейропластичность спинного мозга мышей в условиях антиортостатического вывешивания. Авиакосмическая и Экологическая Медицина 2019; 53(6): 94-7.
  22. Watson C., Harrison M. The location of the major ascending and descending spinal cord tracts in all spinal cord segments in the mouse: actual and extrapolated. Anat. Rec. (Hoboken) 2012; 295(10): 1692-7.
  23. Islamov R.R., Mishagina E.A., Tyapkina O.V. et al. Mechanisms of spinal motoneurons survival in rats under simulated hypogravity on earth. Acta Astronautica 2011; 68: 1469-77.
  24. Tyapkina O.V., Nurullin L.F., Rezvyakov P.N. et al. Myelination disorders in the mechanism of hypogravity motor syndrome development. Biophysics 2012; 57(5): 861-3.
  25. Islamov R.R., Rizvanova A.A., Tyapkina O.V. et al. Genomic study of gene expression in the mouse lumbar spinal cordunder the conditions of simulated microgravity. Doklady Biological Sciences 2011; 439: 197-200.
  26. Povysheva T.V., Rezvyakov P.N., Shaimardanova G.F. et al. Myelinated fibers of the mouse spinal cord after a 30-day space flight. Doklady Biological Sciences 2016; 469: 1-4.
  27. Kozlovskaya I.B., Kreidich Y.V., Oganov V.S. et al. Pathophysiology of motor functions in prolonged manned space flights. Acta Astronautica 1981; 8(9): 1059-72.
  28. Kozlovskaia I.B., Grigoriev A.I. Physiological reactions to muscle loading under conditions of long term hypogravity. Physiologist 1991; 30(1): 76-7.

Copyright (c) 2021 PJSC Human Stem Cells Institute


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: ПИ № ФС 77 - 57156 от 11.03.2014.

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies