Skip to main content
Log in

Morphological Changes and Characteristics of the Expression of Serine Racemase in the Hippocampus of Rats Exposed to Multiple Negative Gravitational Overloads

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Objectives. To study the morphometric parameters and levels of expression of serine racemase in the hippocampus of rats repeatedly exposed to gravitational overloads in the caudocranial direction (–9 Gz). Materials and methods. Rat aged 12 months were subjected to 9-g forces for 5 min twice a day with 12-h intervals for 28 days (group 2, gravity group, n = 10); controls were not exposed to hypergravitation (group 1, controls, n = 10). Morphometric mean areas of the nuclei and perikarya of pyramidal cells were determined, along with the specific number of neurons with signs of damage, the relative areas of pyramidal neuron and neuroglial cell perikarya. Immunohistochemical studies addressed the level of expression of serine racemase in all zones of the hippocampus. Results. Signs of impaired blood supply in the microcirculatory component were seen in the form of spongiosis, thickening of capillary walls, and diapedesis of erythrocytes. All hippocampal zones in experimental rats showed sharp increases in the numbers of pyramidal neurons with signs of damage. Atrophic changes consisting of decreases in the mean and relative areas of neuron perikarya were identified. Immunohistochemical studies showed increased expression of serine racemase in field CA1, along with translocation of immunoreactive material into the processes of pyramidal neurons. Fields CA3 and CA4 showed a tendency to decreases in serine racemase content. Conclusions. Prolonged gravitational exposure in the caudocranial direction led to the appearance of signs of severe damage in all fields of the rat hippocampus, combined with increased expression and accumulation of serine racemase in the dendrites of pyramidal neurons in field CA1, which may be evidence that excitotoxicity is involved in the mechanisms of secondary damage in this zone.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. M. D. Gaevyi, L. E. Nazarova, L. M. Gaevaya, and Yu. A. Ogurtsov, “Reproduction of experimental stroke in experimental studies,” Patol. Fiziol. Eksper. Ter., No. 2, 7–8 ( 2000).

    Google Scholar 

  2. L. M. Makarova, “Neuroprotective action of Mexidol in total cerebral ischemia (the question of the advisability of using this agent in gravitational overloading),” Byul. Eksper. Biol, No. 1, 48–55 ( 2006).

    Google Scholar 

  3. A. V. Smirnov, N. V. Grigor’eva, M. R. Ekova, et al., “Morphological changes and characteristics of the expression of serine racemase in the hippocampus of rats exposed to combined stress,” Morfologiya, 150, No. 6, 20–25 (2017).

    Google Scholar 

  4. A. V. Smirnov, M. V. Shmidt, D. S. Mednikov, et al., “Structural changes in the hippocampus in rats in an experimental model of hypertensive encephalopathy considering the expression of heat shock proteins,” Vestn. Volgograd. Gos. Univ., 60, No. 4, 90–95 (2016).

    Google Scholar 

  5. A. S. Shtemberg, V. S. Kudrin, P. M. Klodt, V. B. Narkevich, and A. S. Bazyan, “The effects of antiorthostatic hypodynamia and overload on discriminant learning and monoamine metabolism in brain structures in mice,” Neirokhimiya, 6, No. 4, 291–298 (2012).

    Google Scholar 

  6. L. Balan, V. N. Foltyn, M. Zehl, E. Dumin, E. Dikopoltsev, D. Knoh, Y. Ohno, A. Kihara, O. N. Jensen, I. S. Radzishevsky, and H. Wolosker, “Feedback inactivation of D-serine synthesis by NMDA receptor-elicited translocation of serine racemase to the membrane,” Proc. Natl. Acad. Sci. USA, 106, No. 18, 7589–7594 (2009).

    Article  CAS  Google Scholar 

  7. A. A. Fedotov, S. A. Akulov, and A. S. Akulova, “Alterations in cardiovascular system under artificially simulated microgravity: preliminary study,” Conf. Proc. IEEE Eng. Med. Biol.Soc, 204–206 (2016).

  8. G. Kolodney, E. Dumin, H. Safory, D. Rosenberg, H. Mori, I. Radzishevsky, and H. Wolosker, “Nuclear compartmentalization of serine racemase regulates D-serine production: Implications for N-methyl-D-aspartate (NMDA) receptor activation,” J. Biol. Chem., 290, No. 52, 31,037–31,050 (2015).

    Article  CAS  Google Scholar 

  9. A. K. Mustafa, A. S. Ahmad, E. Zeynalov, et al., “Serine racemase deletion protects against cerebral ischemia and excitotoxicity,” J. Neuroscience, 30, No. 4, 1413–1416 (2010).

    Article  CAS  Google Scholar 

  10. Y. Nishida, S. Maruyama, I. Shouji, T. Kemuriyama, A. Tashiro, H. Ohta, K. Hagisawa, M. Hiruma, and H. Yokoe, “Effects and biological limitations of +Gz acceleration on the autonomic functions-related circulation in rats,” J. Physiol. Sci., 66, No. 6, 447–462 (2016).

    Article  Google Scholar 

  11. G. Paxinos and C. A. Watson, The Rat Brain in Stereotaxic Coordinates, Academic Press, Toronto (1982).

    Google Scholar 

  12. C. B. Rueda, I. Llorente-Folch, J. Traba, et al., “Glutamate excitotoxicity and Ca2+-regulation of respiration: Role of the Ca2+-activated mitochondrial transporters (CaMCs),” Biochim. Biophys. Acta, 1857, No. 8, 1158–1166 (2016).

    Article  CAS  Google Scholar 

  13. D. Tomassoni, R. Avola, M. A. Di Tullio, and F. Amenta, “Increased expression of glial fibrillary acidic protein in the brain of spontaneously hypertensive rats,” Clin. Exp. Hypertens., 26, No. 4, 335–350 (2004).

    Article  CAS  Google Scholar 

  14. C. C. Tran, G. Ossard, X. Etienne, A. Serra, M. Berthelot, J. C. Jouanin, and C. Y. Guézennec, “Brief exposure to -2 Gz reduces cerebral blood flow velocity during subsequent +2 Gz acceleration,” J. Gravit. Physiol., 11, No. 2, 81–82 (2004).

    Google Scholar 

  15. T. Yoshimura and M. Goto, “D-amino acids in the brain: structure and function of pyridoxal phosphate-dependent amino acid racemases,” FEBS J., 275, No. 14, 3527–3537 (2008).

    Article  CAS  Google Scholar 

  16. Y. N. Zhao, J. M. Li, C. X. Chen, P. Zhang, and S. X. Li, “Hypertension-mediated enhancement of JNK activation in association with endoplasmic reticulum stress in rat model hippocampus with cerebral ischemia-reperfusion,” Genet. Mol. Res., 14, No. 3, 10980–10990 (2015).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to D. S. Mednikov.

Additional information

Translated from Morfologiya, Vol 153, No. 1, pp. 16–22, January–February, 2018.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mednikov, D.S., Smirnov, A.V., Shmidt, M.V. et al. Morphological Changes and Characteristics of the Expression of Serine Racemase in the Hippocampus of Rats Exposed to Multiple Negative Gravitational Overloads. Neurosci Behav Physi 49, 89–94 (2019). https://doi.org/10.1007/s11055-018-0698-x

Download citation

  • Received:

  • Revised:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-018-0698-x

Keywords

Navigation