The dynamics of Sert, Htr4a, and Bdnf genes expression in the blood of rats under chronic stress exposure
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The dynamics of Sert, Htr4a, and Bdnf genes expression in the blood of rats under chronic stress exposure

E.V. Valeeva a,b*, I.I. Semina a**, A.G. Galeeva b,c***, O.A. Kravtsova b****

aKazan State Medical University, Kazan, 420012 Russia

bKazan Federal University, Kazan, 420008 Russia

cFederal Center for Toxicological, Radiation, and Biological Safety, Kazan, 420075 Russia

E-mail: *vevaleeva@ya.ru, **seminai@mail.ru, ***antonina-95@yandex.ru, ****okravz@yandex.ru

Received February 28, 2022

 

ORIGINAL ARTICLE

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DOI: 10.26907/2542-064X.2022.2.196-211

For citation: Valeeva E.V., Semina I.I., Galeeva A.G., Kravtsova O.A. The dynamics of Sert, Htr4a, and Bdnf genes expression in the blood of rats under chronic stress exposure. Uchenye Zapiski Kazanskogo Universiteta. Seriya Estestvennye Nauki, 2022, vol. 164, no. 2, pp. 196–211. doi: 10.26907/2542-064X.2022.2.196-211. (In Russian)

Abstract

In this article, we discuss the expression levels of Sert, Htr4a, and Bdnf genes in the blood of Wistar rats exposed to the following types of chronic stresses for 270 days: swimming with a load and immobilization, as well as the combination of these two stresses. On day 180 of the experiment, the stresses described above triggered an increase in Sert expression in both females and males of all the groups, except the control group. The immobilization stress induced for 270 days caused an increase in the level of Sert expression in females and reduced it in males. In response to the stresses under study, the expression of Htr4a decreased in males, but not females, on day 270. The expression of Bdnf decreased on day 270 in males after the combined stress and in females subjected to immobilization. Thus, the expression levels of some genes involved in the peripheral transmission of serotonin are greatly influenced by chronic stresses and depend on gender, duration of exposure to stress, and type of stress factors.

Keywords: chronic stress, serotonin, gene expression, Sert, Htr4a, Bdnf

Acknowledgments. This study was supported by the Russian Foundation for Basic Research (project no. 19-34-90171).

Figure Captions

Fig. 1. Fold change of genes expression in the blood of rats (log2 FC): a) Sert, serotonin transporter; b) Bdnf, brain-derived neurotrophic factor; c) Htr4a, 5-hydroxytryptamine-4 receptor. Key: PhS – the group exposed to physical stress, IS – the group exposed to immobilization; PhS+IS – the group exposed to the combined stress.

References

  1. Everly J., George S., Jeffrey M. A Clinical Guide to the Treatment of the Human Stress Response. Springer, 2019. 636 p. doi: 10.1007/978-1-4939-9098-6.
  2. van Praag H.M. Can stress cause depression? World J. Biol. Psychiatry, 2005, vol. 6, no. 2, pp. 5–22. doi: 10.1080/15622970510030018.
  3. Beiter R., Nash R., McCrady M., Rhoades D., Linscomb M., Clarahan M., Sammut S. The prevalence and correlates of depression, anxiety, and stress in a sample of college students. J. Affective Disord., 2015, vol. 173, pp. 90–96. doi: 10.1016/j.jad.2014.10.054.
  4. McLoughlin E., Fletcher D., Slavich G.M., Arnold R., Moore L.J. Cumulative lifetime stress exposure, depression, anxiety, and well-being in elite athletes: A mixed-method study. Psychol. Sport Exercise, 2021, vol. 52, art. 101823, pp. 1–21. doi: 10.1016/j.psychsport.2020.101823.
  5. Carrasco G.A., Van de Kar L.D. Neuroendocrine pharmacology of stress. Eur. J. Pharmacol., 2003, vol. 463, nos. 1–3, pp. 235–272. doi: 10.1016/s0014-2999(03)01285-8.
  6. Kanova M., Kohout P. Serotonin – its synthesis and roles in the healthy and the critically ill. Int. J. Mol. Sci., 2021, vol. 22, no. 9, art. 4837, pp. 1–12. doi: 10.3390/ijms22094837.
  7. Mauler M., Bode C., Duerschmied D. Platelet serotonin modulates immune functions. Hämostaseologie, 2016, vol. 36, no. 1, pp. 11–16. doi: 10.5482/HAMO-14-11-0073.
  8. Schoenichen C., Bode C., Duerschmied D. Role of platelet serotonin in innate immune cell recruitment. Front. Biosci.-Landmark, 2019, vol. 24, no. 3, pp. 514–526. doi: 10.2741/4732.
  9. Mercado C.P., Kilic F. Molecular mechanisms of SERT in platelets: Regulation of plasma serotonin levels. Mol. Interventions, 2010, vol. 10, no. 4, pp. 231–241. doi: 10.1124/mi.10.4.6.
  10. Holinstat M. Normal platelet function. Cancer Metastasis Rev., 2017, vol. 36, no. 2, pp. 195–198. doi: 10.1007/s10555-017-9677-x.
  11. Azadmarzabadi E., Haghighatfard A., Mohammadi A. Low resilience to stress is associated with candidate gene expression alterations in the dopaminergic signalling pathway. Psychogeriatrics, 2018, vol. 18, no. 3, pp. 190–201. doi: 10.1111/psyg.12312.
  12. Medina-Martel M., Urbina M., Fazzino F., Lima L. Serotonin transporter in lymphocytes of rats exposed to physical restraint stress. Neuroimmunomodulation, 2013, vol. 20, no. 6, pp. 361–367. doi: 10.1159/000353797.
  13. Herr N., Bode C., Duerschmied D. The effects of serotonin in immune cells. Front. Cardiovasc. Med., 2017, vol. 4, art. 48, pp. 1–11. doi: 10.3389/fcvm.2017.00048.
  14. Meneses A. 5-HT systems: Emergent targets for memory formation and memory alterations. Rev. Neurosci., 2013, vol. 24, no. 6, pp. 629–664. doi: 10.1515/revneuro-2013-0026.
  15. Bai M., Zhu X.Z., Zhang Y., Zhang S., Zhang L., Xue L., Zhong M., Zhang X. Anhedonia was associated with the dysregulation of hippocampal HTR4 and microRNA Let-7a in rats. Physiol. Behav., 2014, vol. 129, pp. 135–141. doi: 10.1016/j.physbeh.2014.02.035.
  16. Huang E.J., Reichardt L.F. Neurotrophins: Roles in neuronal development and function. Annu. Rev. Neurosci., 2001, vol. 24, pp. 677–736. doi: 10.1146/annurev.neuro.24.1.677.
  17. Boukhatem I., Fleury S., Welman M., Le Blanc J., Thys C., Freson K., Best M.G., Würdinger T., Allen B.G., Lordkipanidzé M. The brain-derived neurotrophic factor prompts platelet aggregation and secretion. Blood Adv., 2021, vol. 5, no. 18, pp. 3568–3580. doi: 10.1182/bloodadvances.2020004098.
  18. Lommatzsch M., Zingler D., Schuhbaeck K., Schloetcke K., Zingler C., Schuff-Werner P., Virchow J.C. The impact of age, weight and gender on BDNF levels in human platelets and plasma. Neurobiol. Aging, 2005, vol. 26, no. 1, pp. 115–123. doi: 10.1016/j.neurobiolaging.2004.03.002.
  19. Bath K.G., Schilit A., Lee F.S. Stress effects on BDNF expression: Effects of age, sex, and form of stress. Neuroscience, 2013, vol. 239, pp. 149–156. doi: 10.1016/j.neuroscience.2013.01.074.
  20. Mojtabavi H., Saghazadeh A., van den Heuvel L., Bucker J., Rezaei N. Peripheral blood levels of brain-derived neurotrophic factor in patients with post-traumatic stress disorder (PTSD): A systematic review and meta-analysis. PLoS One, 2020, vol. 15, no. 11, art. e0241928, pp. 1–15. doi: 10.1371/journal.pone.0241928.
  21. Beaton J.R., Feleki V. Effect of diet and water temperature on exhaustion time of swimming rats. Can. J. Physiol. Pharmacol., 1967, vol.45, no. 2, pp. 360–363. doi: 10.1139/y67-042.
  22. Bhatia N., Jaggi A.S., Singh N., Anand P., Dhawan R. Adaptogenic potential of curcumin in experimental chronic stress and chronic unpredictable stress-induced memory deficits and alterations in functional homeostasis. J. Nat. Med., 2011, vol. 65, nos. 3–4, pp. 532–543. doi: 10.1007/s11418-011-0535-9.
  23. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods, 2001, vol. 25, no. 4, pp. 402–408. doi: 10.1006/meth.2001.1262.
  24. Dhabhar F.S. Effects of stress on immune function: the good, the bad, and the beautiful. Immunol. Res., 2014, vol. 58, no. 3, pp. 193–210. doi: 10.1007/s12026-014-8517-0.
  25. Agorastos A., Pervanidou P., Chrousos G.P., Kolaitis G. Early life stress and trauma: Developmental neuroendocrine aspects of prolonged stress system dysregulation. Hormones (Athens), 2018, vol. 17, no. 4, pp. 507–520. doi: 10.1007/s42000-018-0065-x.
  26. Valeeva E.V., Semina I.I., Galeeva A.G., Mukhametshina A.D., Mukhametshina R.D., Kravtsova O.A. Effect of chronic stress on the relative level of dopamine receptor gene expression. Kazan. Med. Zh., 2022, vol. 103, no. 3, pp. 418–426. doi: 10.17816/KMJ2022-418. (In Russian)
  27. Faraj B.A., Olkowski Z.L., Jackson R.T. Expression of a high-affinity serotonin transporter in human lymphocytes. Int. J. Immunopharmacol., 1994, vol. 16, no. 7, pp. 561–567. doi: 10.1016/0192-0561(94)90107-4.
  28. Tafet G.E., Toister-Achituv M., Shinitzky M. Enhancement of serotonin uptakeby cortisol: A possible link between stress and depression. Cognit., Affective, Behav. Neurosci., 2001, vol. 1, no. 1, pp. 96–104. doi: 10.3758/cabn.1.1.96.
  29. Couch Y., Anthony D.C., Dolgov O., Revischin A., Festoff B., Santos A.I., Steinbusch H.W., Strekalova T. Microglial activation, increased TNF and SERT expression in the prefrontal cortex define stress-altered behaviour in mice susceptible to anhedonia. Brain, Behav., Immun., 2013, vol. 29, pp. 136–146. doi: 10.1016/j.bbi.2012.12.017.
  30. Takaki A., Huang Q.H., Somogyvári-Vigh A., Arimura A. Immobilization stress may increase plasma interleukin-6 via central and peripheral catecholamines. Neuroimmunomodulation, 1994, vol. 1, no. 6, pp. 335–342. doi: 10.1159/000097185.
  31. Powell N.D., Bailey M.T., Mays J.W., Stiner-Jones L.M., Hanke M.L., Padgett D.A., Sheridan J.F. Repeated social defeat activates dendritic cells and enhances Toll-like receptor dependent cytokine secretion. Brain, Behav., Immun., 2009, vol. 23, no. 2, pp. 225–231. doi: 10.1016/j.bbi.2008.09.010.
  32. Nishizawa S., Benkelfat C., Young S.N., Leyton M., Mzengeza S., de Montigny C., Blier P., Diksic M. Differences between males and females in rates of serotonin synthesis in human brain. Proc. Natl. Acad. Sci. U. S. A., 1997, vol. 94, no. 10, pp. 530–5313. doi: 10.1073/pnas.94.10.5308.
  33. Mitsushima D., Yamada K., Takase K., Funabashi T., Kimura F. Sex differences in the basolateral amygdala: The extracellular levels of serotonin and dopamine, and their responses to restraint stress in rats. Eur. J. Neurosci., 2006, vol. 24, no. 11, pp. 3245–3254. doi: 10.1111/j.1460-9568.2006.05214.x.
  34. Wei J., Yuen E.Y., Liu W., Li X., Zhong P., Karatsoreos I.N., McEwen B.S., Yan Z. Estrogen protects against the detrimental effects of repeated stress on glutamatergic transmission and cognition. Mol. Psychiatry, 2014, vol. 19, no. 5, pp. 588–598. doi: 10.1038/mp.2013.83.
  35. Pooley A.E., Benjamin R.C., Sreedhar S., Eagle A.L., Robison A.J., Mazei-Robison M.S., Breedlove S.M., Jordan C.L. Sex differences in the traumatic stress response: PTSD symptoms in women recapitulated in female rats. Biol. Sex Differ., 2018, vol. 9, no. 1, art. 31, pp. 1–11. doi: 10.1186/s13293-018-0191-9.
  36. Compan V., Zhou M., Grailhe R., Gazzara R.A., Martin R., Gingrich J., Dumuis A., Brunner D., Bockaert J., Hen R. Attenuated response to stress and novelty and hypersensitivity to seizures in   5-HT4 receptor knock-out mice. J. Neurosci., 2004, vol. 24, no. 2, pp. 412–419. doi: 10.1523/jneurosci.2806-03.2004.
  37. Segu L., Lecomte M.J., Wolff M., Santamaria J., Hen R., Dumuis A., Berrard S., Bockaert J., Buhot M.C., Compan V. Hyperfunction of muscarinic receptor maintains long-term memory in    5-HT4 receptor knock-out mice. PLoS One, 2010, vol. 5, no. 3, art. e9529, pp. 1–8. doi: 10.1371/journal.pone.0009529.
  38. Murphy S.E., De Cates A.N., Gillespie A.L., Godlewska B.R., Scaife J.C., Wright L.C., Cowen P.J., Harmer C.J. Translating the promise of 5HT4 receptor agonists for the treatment of depression. Psychol. Med., 2021, vol. 51, no. 7, pp. 1111–1120. doi: 10.1017/S0033291720000604.
  39. Yang G.B., Qiu C.L., Zhao H., Liu Q., Shao Y. Expression of mRNA for multiple serotonin (5-HT) receptor types/subtypes by the peripheral blood mononuclear cells of rhesus macaques. J. Neuroimmunol., 2006, vol. 178, nos. 1–2, pp. 24–29. doi: 10.1016/j.jneuroim.2006.05.016.
  40. Cadegiani F.A., Kater C.E. Basal hormones and biochemical markers as predictors of overtraining syndrome in male athletes: The EROS-BASAL study. J. Athletic Train., 2019, vol. 54, no. 8, pp. 906–914. doi: 10.4085/1062-6050-148-18.
  41. Perfalk E., da Cunha-Bang S., Holst K.K., Keller S., Svarer C., Knudsen G.M., Frokjaer V.G. Testosterone levels in healthy men correlate negatively with serotonin 4 receptor binding. Psychoneuroendocrinology, 2017, vol. 81, pp. 22–28. doi: 10.1016/j.psyneuen.2017.03.018.
  42. Karege F., Schwald M., Cisse M. Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets. Neurosci. Lett., 2002, vol. 328, no. 3, pp. 261–264. doi: 10.1016/s0304-3940(02)00529-3.
  43. Elhwuegi A.S. Central monoamines and their role in major depression. Prog. Neuro-Psychopharmacol. Biol. Psychiatry, 2004, vol. 28, no. 3, pp. 435–451. doi: 10.1016/j.pnpbp.2003.11.018.
  44. Peng S., Li W., Lv L., Zhang Z., Zhan X. BDNF as a biomarker in diagnosis and evaluation of treatment for schizophrenia and depression. Discovery Med., 2018, vol. 26, no. 143, pp. 127–136.
  45. Nieto R.R., Carrasco A., Corral S., Castillo R., Gaspar P.A., Bustamante M.L., Silva H. BDNF as a biomarker of cognition in schizophrenia/psychosis: An updated review. Front. Psychiatry, 2021, vol. 12, art. 662407, pp. 1–9. doi: 10.3389/fpsyt.2021.662407.
  46. Sweeten B.L.W., Sutton A.M., Wellman L.L., Sanford L.D. Predicting stress resilience and vulnerability: Brain-derived neurotrophic factor and rapid eye movement sleep as potential biomarkers of individual stress responses. Sleep, 2020, vol. 43, no. 1, art. zsz199, pp. 1–12. doi: 10.1093/sleep/zsz199.
  47. Nakagawa Y., To M., Saruta J., Yamamoto Y., Yamamoto T., Shimizu T., Kamata Y., Matsuo M., Tsukinoki K. Effect of social isolation stress on saliva BDNF in rat. J. Oral Sci., 2019, vol. 61, no. 4, pp. 516–520. doi: 10.2334/josnusd.18-0409.
  48. Nooshinfar E., Akbarzadeh-Baghban A., Meisami E. Effects of increasing durations of immobilization stress on plasma corticosterone level, learning and memory and hippocampal BDNF gene expression in rats. Neurosci. Lett., 2011, vol. 500, no. 1, pp. 63–66. doi: 10.1016/j.neulet.2011.05.243.

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