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Characteristic of morphological changes in gyrus dentatus at the pharmacological correction of depressive status in adultrats

[Experimental medicine]
Alexey Vladimirovich Smirnov; Maria Rafaelovna Ekova; Ivan Nikolaevich Tyurenkov; Elena Vladimirovna Volotova;

When modeling depression in 12 months age rats, structural changes in the granular layer of dentate gyrus were studied, and the possibility of pharmacological correction of the revealed changes with phenibut and compounds with laboratory codes of RGPU-189 (salifen – adduct of γ-amino-β-phenylbutyric and salicylic acids), RGPU-135 (neuroglutam – β-phenyl derivative of glutamic acid). 5 groups of 10 animals each were formed: control rats; rats subjected to daily 30-minute stress for 7 days; stressed rats treated with phenibut, with RGPU-189, with RGPU-135. Depressive state was caused in animals by simulating mild stress in a special installation, which consists of 6 isolated compartments of the same volume, allowing combining several stressful stimuli (pulsating light, loud sound, vibration). After stress exposure in animals in granular layer of dentate gyrus an increase in specific number of hyperchromatic neurons and specific number of wrinkled hyperchromatic neurons was observed. The use of the compound RGPU-189 to a greater extent had a corrective effect, since it helped to reduce both reversible and irreversible changes in neurons.


1. Zhou Y., Ma C., Li B.-M., Sun C. Polygala japonica Houtt. reverses depression-like behavior and restores reduced hippocampal neurogenesis in chronic stress mice. Biomedicine & Pharmacotherapy. 2018;99:986-996. https://doi.org/10.1016/j.biopha.2018.01.133
2. Park S.-C. Neurogenesis and antidepressant action. Cell and Tissue Research. 2019;377:95-106. https://doi.org/10.1007/s00441-019-03043-5
3. Murata K., Fujita N., Takahashi R., Inui A. Ninjinyoeito improves behavioral abnormalities and hippocampal neurogenesis in the corticosterone model of depression. Front. Pharmacol. 2018;9:12-16. https://doi.org/10.3389/fphar.2018.01216
4. Datson N. A., Speksnijder N., Mayer J. L., Steenbergen P. J., Korobko O. [et al.]. The transcriptional response to chronic stress and glucocorticoid receptor blockade in the hippocampal dentate gyrus. Hippocampus. 2012;22(2):359-371. https://doi.org/10.1002/hipo.20905
5. Ekova M. R., Smirnov A. V., Shmidt M. V., Tyurenkov I. N., Volotova E. V. [et al.]. Сomparison of morphofunctional features of the ventral hippocampus in adult and old rats after combined stress. Advances in Gerontology. 2016;6(3):204-211. https://doi.org/10.1134/S2079057016030036
6. Amaral D. G., Scharfman H. E., Lavenex P. The dentate gyrus: fundamental neuroanatomical organization (dentate gyrus for dummies). Prog. Brain. Res. 2007;163:3-22. https://doi.org/10.1016/S0079-6123(07)63001-5
7. Tawarayama H. Novel function of the chemorepellent draxin as a regulator for hippocampal neurogenesis. Neural. Regen. Res. 2018;13:799-800. https://doi.org/10.4103/1673-5374.232465
8. Wu Y. P., Gao H. Y., Ouyang S. H., Kurihara H., He R. R., Li Y. F. Predator stress-induced depression is associated with inhibition of hippocampal neurogenesis in adult male mice. Neural. Regen. Res. 2019;14(2):298-305. https://doi.org/10.4103/1673-5374.244792
9. Tyurenkov I. N., Bagmetova V. V., Chernysheva Y. V., Borodin D. D. A depressive state in rats in chronic combined stress induced by combined stresses of different modalities. Neuroscience and behavioral physiology. 2015;45(5):542-549. https://doi.org/10.1007/s11055-015-0108-6
10. Paxinos G., Watson C. The rat brain in stereotaxic coordinates. 6th ed. New York (NY): Elsevier Academic Press, 2007.
11. Baturin V. A., Fisher V. V., Sergeev S. A., Yatsuk I. V. Premedication and mexidol impact on cortisol levels and endothelial function in operating stress. Meditsinskii vestnik Severnogo Kavkaza. – Medical News of North Caucasus. 2015;10(1):99100. (In Russ.). http://doi.org/10.14300/mnnc.2015.10019
12. Llorens-Martın M., Trejo J. L. Mifepristone prevents stress-induced apoptosis in newborn neurons and increases AMPA receptor expression in the dentate gyrus of C57/BL6 mice. PLoS ONE. 2011;6(11):e28376. https://doi.org/10.1371/journal.pone.0028376
13. Micheli L., Ceccarelli M., D’Andrea G., Tirone F. Depression and adult neurogenesis: Positive effects of the antidepressant fluoxetine and of physical exercise. Brain Research Bulletin. 2018;143:181-193. https://doi.org/10.1016/j.brainresbull.2018.09.002
14. Schoenfeld T. J., Gould E. Stress, stress hormones, and adult neurogenesis. Exp. Neurol. 2012;233(1):12‑21. https://doi.org/10.1016/j.expneurol.2011.01.008
15. Aimone J. B., Li Y., Lee S. W., Clemenson G. D., Deng W., Gage F. H. Regulation and function of adult neurogenesis: from genes to cognition. Physiol. Rev. 2014;94:991‑1026. https://doi.org/10.1152/physrev.00004.2014
16. Fitzsimons C. P., van Hooijdonk L. W., Schouten M., Zalachoras I., Brinks V. [et al.]. Knockdown of the glucocorticoid receptor alters functional integration of newborn neurons in the adult hippocampus and impairs fear-motivated behavior. Mol. Psychiatry. 2013;18:993-1005. https://doi.org/10.1038/mp.2012.123
17. Taliaz D., Stall N., Dar D. E., Zangen A. Knockdown ofbrain-derived neurotrophic factor in specific brain sites precipitates behaviors associated with depression and reduces neurogenesis. Mol. Psychiatry. 2010;15:80-92. https://doi.org/10.1038/mp.2009.67
18. Maekawa M., Namba T., Suzuki E., Yuasa S., Kohsaka S., Uchino S. NMDA receptor antagonist memantine promotes cell proliferation and production of mature granule neurons in the adult hippocampus. Neurosci. Res. 2009;63:259-266. https://doi.org/10.1016/j.neures.2008.12.006
19. Schoenfeld T. J., Gould E. Differential effects of stress and glucocorticoids on adult neurogenesis. Curr. Top. Behav. Neurosci. 2013;15:139-64. https://doi.org/10.1007/7854_2012_233
20. Pathania M., Yan L. D., Bordey A. A. A symphony of signals conducts early and late stages of adult neurogenesis. Neuropharmacology. 2010;58:865-876. https://doi.org/10.1016/j.neuropharm.2010.01.010
21. Sun B., Halabisky B., Zhou Y., Palop J. J., Yu G. [et al.]. Imbalance between GABAergic and glutamatergic transmission impairs adult neurogenesis in an animal model of Alzheimer’s disease. Cell. Stem. Cell. 2009;5:624-633. https://doi.org/10.1016/j.stem.2009.10.003

Keywords: dentate gyrus, depression, stress, phenibut, glutamic acid and GABA derivatives, rat

Stavropol State Medical Academy
Pyatigorsk State Research Institute of Balneotherapeutics
Pyatigorsk State Pharmaceutical Academy