MORPHOLOGICAL CHANGES AND PECULIARITIES OF SERINE RACEMASE EXPRESSION IN THE HIPPOCAMPUS OF RATS EXPOSED TO REPEATED NEGATIVE GRAVITATIONAL OVERLOADS

Abstract

Objective - to study the morphometric parameters and serine racemase expression in the hippocampus of rats exposed to repeated gravitational overloads in caudo-cranial direction (-9 Gz). Material and methods. 12 months-old rats were exposed to a force of 9G for 5 min twice daily with an interval of 12 h for 28 days - group 2 (exposure to gravitation, n=10). Rats not affected by hypergravitation formed group 1 (control, n=10). Morphometric methods were used to calculate an average size of the cell nuclei and perikarya of pyramidal neurons, the proportion of neurons with the signs of damage, the relative areas of pyramidal neuron perikarya and neuropil. Immunohistochemically the level of serine racemase expression was studied in all the hippocampal areas. Results. The signs of cerebral microcirculatory disorders were detected such as spongiosis, capillary wall thickening, erythrocyte diapedesis. In all the zones of the hippocampus significant increase in number of pyramidal neurons with the signs of injury was observed. The atrophic changes were demonstrated by the decrease in the average and relative areas of pyramidal neuron perikarya in all the hippocampal areas. Immunohistochemical study has shown the increase in serine racemase expression in CA1, as well as translocation of immunoreactive material into the processes of pyramidal neurons. In CA3 and CA4, a tendency to decreased expression of serine racemase was found. Conclusions. Following a long-term exposure of rats to gravitational overloads in caudo-cranial direction, all the hippocampal areas demonstrated the signs of damage combined with an enhanced expression and accumulation serine racemase in the dendrites of pyramidal neurons of the CA1 area, which may indicate the participation of excitotoxicity in the mechanisms of secondary damage in this area.

Keywords

hippocampus / gravitational force / serine racemase / rat

References

[1] Гаевый М. Д., Назарова Л. Е., Гаевая Л.М, Огурцов Ю. А. Воспроизведение геморрагического инсульта в эксперименте // Патол. физиол. и экспер. тер. 2000. № 2. С. 7-8.

[2] Макарова Л. М. Нейропротективное действие препарата «мексидол» при тотальной ишемии мозга (к вопросу о целесообразности применения данного препарата при гравитационных перегрузках) // Бюл. экспер. биол. 2006. № 1. С. 48-55.

[3] Смирнов А. В., Григорьева Н. В., Экова М. Р., Шмидт М. В., Медников Д. С., Тюренков И. Н., Куркин Д. В., Волотова Е. В. Морфологические изменения и особенности экспрессии сериновой рацемазы в гиппокампе крыс при комбинированном стрессорном воздействии // Морфология. 2016. Т. 150, вып. 6. С. 20-25.

[4] Смирнов А. В., Шмидт М. В., Медников Д. С., Экова М. Р., Тюренков И. Н., Куркин Д. В., Волотова Е. В. Структурные изменения гиппокампа крыс при экспериментальном моделировании гипертензивной энцефалопатии с учетом экспрессии белков теплового шока // Вестн. ВолгГМУ. 2016. Т. 60, № 4. С. 90-95.

[5] Штемберг А. С., Кудрин В. С., Клодт П. М., Наркевич В. Б., Базян А. С. Влияние антиортостатической гиподинамии и перегрузки на дискриминантное обучение и обмен моноаминов в структурах мозга мышей // Нейрохимия. 2012. Т. 29, № 4. С. 318-326.

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

[7] Fedotov A. A., Akulov S. A., Akulova A. S. Alterations in cardiovascular system under artificially simulated microgravity: preliminary study // Conf. Proc. IEEE Eng. Med. Biol. Soc. 2016. P. 204-206.

[8] Kolodney G., Dumin E., Safory H., Rosenberg D., Mori H., Radzishevsky I., Wolosker H. Nuclear Compartmentalization of Se rine Racemase Regulates D-Serine Production: Implications for N-methyl-D-aspartate (NMDA) receptor activation // J. Biol. Chem. 2015. Vol. 290, № 52. P. 31037-31050.

[9] Mustafa A. K., Ahmad A. S., Zeynalov E., Gazi S. K., Sikka G., Ehmsen J. T., Barrow R. K., Coyle J. T., Snyder S. H., Dore S. Serine racemase deletion protects against cerebral ischemia and excitotoxicity // J. Neurosci. 2010. Vol. 30, № 4. Р. 1413-1416.

[10] Nishida Y., Maruyama S., Shouji I., Kemuriyama T., Tashiro A., Ohta H., Hagisawa K., Hiruma M., Yokoe H. Effects and biological limitations of +Gz acceleration on the autonomic functionsrelated circulation in rats // J. Physiol. Sci. 2016. Vol. 66, № 6. Р. 447-462.

[11] Paxinos G., Watson C.А. The rat brain in stereotaxic coordinates // Toronto: Acad. Press, 1982. 90 p.

[12] Rueda C. B., Llorente-Folch I., Traba J., Amigo I., Gonzalez-Sanchez P., Contreras L., Juaristi I., Martinez-Valero P., Pardo B., Del Arco A., Satrustegui J. Glutamate excitotoxicity and Ca2+-regulation of respiration: Role of the Ca2+ activated mitochondrial transporters (CaMCs) // Biochim. Biophys. Acta. 2016. Vol. 1857, № 8. Р. 1158-1166.

[13] Tomassoni D., Avola R., Di Tullio M. A., Amenta F. Increased expression of glial fibrillary acidic protein in the brain of spontaneously hypertensive rats // Clinical and experimental hypertension. 2004. Vol. 26, № 4. Р. 335-350.

[14] Tran C. C., Ossard G., Etienne X., Serra A., Berthelot M., Jouanin J. C., Guézennec C. Y. Brief exposure to -2 Gz reduces cerebral blood flow velocity during subsequent +2 Gz acceleration // J. Gravit. Physiol. 2004. Vol. 11, № 2. P. 81-82.

[15] Yoshimura T., Goto M. D-amino acids in the brain: structure and function of pyridoxal phosphate-dependent amino acid racemases // FEBS J. 2008. Vol. 275, № 14. Р. 3527-3537.

[16] Zhao Y. N., Li J. M., Chen C. X., Zhang P., Li S. X. Hypertensionmediated enhancement of JNK activation in association with endoplasmic reticulum stress in rat model hippocampus with cerebral ischemia-reperfusion // Genet Mol Res. 2015. Vol. 14, № 3. Р. 10980-10990.

RIGHTS & PERMISSIONS

Eco-Vector