Slc6a4, Tph2, Htr1b, Htr2a genes expression in the mouse spinal cord after microgravity exposure simulation on earth
- Authors: Kuznetsov MS1, Lisyukov AN1, Davleeva MA1, Izmailov AA1
-
Affiliations:
- Kazan State Medical University
- Issue: Vol 101, No 5 (2020)
- Pages: 698-703
- Section: Experimental medicine
- URL: https://kazanmedjournal.ru/kazanmedj/article/view/34243
- DOI: https://doi.org/10.17816/KMJ2020-698
- ID: 34243
Cite item
Abstract
Aim. To determine the level of gene expression of the serotonergic neurotransmission system (Slc6a4, Tph2, Htr1b, Htr2a) in the cervical and lumbar enlargement of the spinal cord for mice after 30-day microgravity exposure simulation by using the antiorthostatic unloading model by Morey-Holton et al. and a subsequent 7-dayrecovery period.
Methods. The experimental animals were divided into three groups: “Unloading” group with mice undergoes hindlimb-unloading procedure for 30 days (n=5); “Recovery” group with mice undergoes hindlimb-unloading procedure for 30 days, followed by readaptation within 7 days (n=5); “Control” group with mice kept at standard vivarium conditions (n=5). The expression level of genes encoding synaptic proteins in the central nervous system was estimated by a real-time polymerase chain reaction.
Results. There were no statistically significant differences between the studied groups regarding the Tph2, Htr1b, and Htr2a expressions in the cervical and lumbar enlargement of the spinal cord. Compared to the “Control” group, a statistically significant increase (6.3 times) in the level of Slc6a4 expression in the lumbar spinal cord was revealed after microgravity exposure simulation (“Unloading” group), followed by a 3-fold decrease during the readaptation period (“Recovery” group ).
Conclusion. The expression level of the Slc6a4 gene, which encodes carrier protein involved in the function of serotonergic synapses, may indicate the potential involvement of this neurotransmitter system in the pathogenesis of movement disorders after microgravity exposure simulation on earth.
Full Text
About the authors
M S Kuznetsov
Kazan State Medical University
Author for correspondence.
Email: qmaxksmu@yandex.ru
Russian Federation, Kazan, Russia
A N Lisyukov
Kazan State Medical University
Email: qmaxksmu@yandex.ru
Russian Federation, Kazan, Russia
M A Davleeva
Kazan State Medical University
Email: qmaxksmu@yandex.ru
Russian Federation, Kazan, Russia
A A Izmailov
Kazan State Medical University
Email: qmaxksmu@yandex.ru
Russian Federation, Kazan, Russia
References
- Edgerton V.R., Roy R.R. Invited review: gravitational biology of the neuromotor systems: a perspective to the next era. J. Appl. Physiol. 2000; 89: 1224–1231. doi: 10.1152/jappl.2000.89.3.1224.
- Hides J., Lambrecht G., Ramdharry G. et al. Parallels between astronauts and terrestrial patients — Taking physiotherapy rehabilitation “To infinity and beyond”. Musculoskelet. Sci. Pract. 2017; 27 (1): S32–S37. doi: 10.1016/j.msksp.2016.12.008.
- Scott J.M., Warburton D.E.R., Williams D. et al. Challenges, concerns and common problems: physiological consequences of spinal cord injury and microgravity. Spinal Cord. 2011; 49: 4–16. doi: 10.1038/sc.2010.53.
- Kuznetsov M.S., Lisukov 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. doi: 10.3389/fphar.2019.00747.
- Lisyukov A.N., Izmaylov A.A., Kuznetsov M.S. et al. Spinal cord neuroplasticity in tail-suspended mice. Aviakosmicheskaya i ekologicheskaya meditsina. 2019; 53 (6): 94–97. (In Russ.) doi: 10.21687/0233-528X-2019-53-6-94-97.
- Perrin F.E., Noristani H.N. Serotonergic mechanisms in spinal cord injury. Exp. Neurol. 2019; 318: 174–191. doi: 10.1016/j.expneurol.2019.05.007.
- Cope T.C. Motor neurobiology of the spinal cord. 1 ed. CRC Press. 2001; 360 р.
- Gackière F., Vinay L. Serotonergic modulation of post-synaptic inhibition and locomotor alternating pattern in the spinal cord. Front. Neural. Circuits. 2014; 8: 102. doi: 10.3389/fncir.2014.00102.
- Ghosh M., Pearse D.D. The role of the serotonergic system in locomotor recovery after spinal cord injury. Front. Neural. Circuits. 2014; 8: 151. doi: 10.1016/j.expneurol.2019.05.007.
- Bardoni R. Serotonergic modulation of nociceptive circuits in spinal cord dorsal horn. Curr. Neuropharmacol. 2019; 17: 1133–1145. doi: 10.2174/1570159X17666191001123900.
- Murphy D.L., Moya P.R. Human serotonin transporter gene (SLC6A4) variants: their contributions to understanding pharmacogenomic and other functional G×G and G×E differences in health and disease. Curr. Opin. Pharmacol. 2011; 11: 3–10. doi: 10.1016/j.coph.2011.02.008.
- Pratelli M., Pasqualetti M. Serotonergic neurotransmission manipulation for the understanding of brain development and function: Learning from Tph2 genetic models. Biochimie. 2019; 161: 3–14. doi: 10.1016/j.biochi.2018.11.016.
- Palacios J.M. Serotonin receptors in brain revisited. Brain Res. 2016; 1645: 46–49. doi: 10.1016/j.brainres.2015.12.042.
- D’Amico J.M., Li Y., Bennett D.J. et al. Reduction of spinal sensory transmission by facilitation of 5-HT1B/D receptors in noninjured and spinal cord-injured humans. J. Neurophysiol. 2013; 109: 1485–1493. doi: 10.1152/jn.00822.2012.
- Gackière F., Vinay L. Serotonergic modulation of post-synaptic inhibition and locomotor alternating pattern in the spinal cord. Front. Neural Circuits. 2014; 8: 102. doi: 10.3389/fncir.2014.00102.
- Genin A.M., Ilyin E.A., Kaplansky A.S. Bioethic rules of research with humans and animals in aviation, space and marine medicine. Aviakosmicheskaya i ekologicheskaya meditsina. 2001; 35 (4):14–20. (In Russ.)
- Morey-Holton E.R., Globus R.K. Hindlimb unloading rodent model: technical aspects. J. Appl. Physiol. 2002; 92: 1367–1377. doi: 10.1152/japplphysiol.00969.2001.
- Andreev-Andrievskiy A., Popova A., Boyle R. et al. Mice in Bion-M 1 space mission: Training and selection. PLoS One. 2014; 9 (8): e104830. doi: 10.1371/journal.pone.0104830.
- R: A Language and Environment for Statistical Computing. Foundation for Statistical Computing. Austria, Vienna. 2017. Available online www.r-project.org (access date: 14.02.2019).
- Bos R., Sadlaoud K., Boulenguez P. et al. Activation of 5-HT2A receptors upregulates the function of the neuronal K-Cl cotransporter KCC2. Proc. Natl. Acad. Sci. USA. 2013; 2 (110 (1)): 348–353. doi: 10.1073/pnas.1213680110.
- Gerin C.G., Hill A., Hill S. et al. Serotonin release variations during recovery of motor function after a spinal cord injury in rats. Synapse. 2010; 64 (11): 855–861. doi: 10.1002/syn.20802.
- Hayashi Y., Jacob-Vadakot S., Dugan E.A. et al. 5-HT precursor loading, but not 5-HT receptor agonists, increases motor function after spinal cord contusion in adult rats. Exp. Neurol. 2010; 221 (1): 68–78. doi: 10.1016/j.expneurol.2009.10.003.