Skip to main content
SpringerLink
Log in

Differential Effect of Male Rat’s PTSD-Like or Depression-Like Status before Mating on the Activity of the Hypothalamic–Pituitary–Adrenal Axis of Adult Offspring

  • Experimental Papers
  • Published:
Journal of Evolutionary Biochemistry and Physiology Aims and scope Submit manuscript

Abstract

There are now a growing number of observations on the transgenerational impact of paternal stress on various offspring functions without involving direct interaction between offspring and father. In the offspring of parents who suffered from posttraumatic stress disorder (PTSD) have been observed an increase in PTSD-like symptoms. In experiments where a chronically elevated level of corticosterone was created in male mice during the entire period of spermatogenesis, a decrease in the stress reactivity of the hypothalamic–pituitary–adrenal (HPA) axis in the offspring of both sexes was shown. However, PTSD in patients creates a reduced level of glucocorticoids in the blood, and there are no experimental data on the effect of modeling PTSD in fathers on the activity of HPA axis of the offspring. The current study examined the relative influences of PTSD-like status (“stress–restress” paradigm) and depression-like status (“learned helplessness” paradigm) in male rats before mating on the HPA axis activity of their adult offspring. In addition to HPA axis activity, the expression of glucocorticoid receptors (GR) in the offspring was analyzed by quantitative immunocytochemistry in the hippocampus and medial prefrontal cortex (mPFC). We demonstrated that in female offspring of fathers with a PTSD-like or depressive-like status there is a decrease in basal and stress activity of the HPA axis in response to 30-min immobilization, which was accompanied by an increase in GR expression in the hippocampus and the 2nd layer mPFC. A similar profile of HPA axis activity was found in male offspring of fathers with modeling of PTSD. However, in male offspring of fathers with a depression-like status, the sensitivity of HPA axis to feedback signals decreased and was accompanied by a decrease in GR expression in the hippocampus and the 2nd layer of mPFC. We concluded that the PTSD- or depression-like status of male rats during the period of spermatogenesis has a differential effect on HPA axis activity and GR expression in the brain of their male offspring.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.
Fig. 2.

Similar content being viewed by others

REFERENCES

  1. Yehuda R, Teicher MH, Seckl JR, Grossman RA, Morris A, Bierer LM (2007) Parental posttraumatic stress disorder as a vulnerability factor for low cortisol trait in offspring of Holocaust survivors. Archiv Gen Psychiatry 64: 1040–1048. https://doi.org/10.1001/archpsyc.64.9.1040

    Article  CAS  Google Scholar 

  2. Yehuda R, Blair W, Labinsky E, Bierer LM (2007) Effects of parental PTSD on the cortisol response to dexamethasone administration in their adult offspring. Am J Psychiatry164: 163–166. https://doi.org/10.1176/ajp.2007.164.1.163

    Article  PubMed  Google Scholar 

  3. Rodgers AB, Morgan CP, Bronson SL, Revello S, Bale TL (2013) Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. J Neurosci 33: 9003–9012. https://doi.org/10.1523/JNEUROSCI.0914-13.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Rodgers AB, Bale TL (2015) Germ cell origins of Posttraumatic stress disorder risk: the transgenerational impact of parental stress experience. Biol Psychiatry 78: 307–314. https://doi.org/10.1016/j.biopsych.2015.03.018

    Article  PubMed  PubMed Central  Google Scholar 

  5. Ordyan NE, Pivina SG, Akulova VK, Kholova GI (2021) Changes in the nature of behavior and the activity of the hypophyseal-adrenocortical system in the offspring of paternal rats subjected to stress in the stress–restress paradigm before mating. Neurosci Behav Physiol 51: 528–534. https://doi.org/10.1007/s11055-021-01100-7

    Article  CAS  Google Scholar 

  6. Andreasen NC (2011) What is post-traumatic stress disorder? Dialog Clin Neurosci 13: 240–243. https://doi.org/10.31887/DCNS.2011.13.2/nandreasen

    Article  Google Scholar 

  7. Whirledge S, Cidlowski JA (2017) Glucocorticoids and reproduction: traffic control on the road to reproduction. Trends Endocrinol Metab 28: 399–415. https://doi.org/10.1016/j.tem.2017.02.005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Pivina SG, Rakitskaya VV, Akulova VK, Ordyan NE (2016) Activity of the hypothalamic–pituitary–adrenal system in prenatally stressed male rats on the experimental model of post-traumatic stress disorder. Bull Exp Biol Med 160: 601–604. https://doi.org/10.1007/s10517-016-3227-3

    Article  CAS  PubMed  Google Scholar 

  9. Czén B, Fuchs E, Wiborg O, Simon M (2016) Animal models of major depression and their clinical implications. Progress Neuropsyhopharmacol Biol Psychiatry 64: 293–310. https://doi.org/10.1016/j.pnpbp.2015.04.004

    Article  Google Scholar 

  10. Mironova V, Pivina SG, Rybnikova E (2013) Effect of inescapable stress in rodent models of depression and posttraumatic stress disorder on CRH and vasopressin immunoreactivity in the hypothalamic paraventricular nucleus. Acta Physiol Hungar 100: 395–410. https://doi.org/10.1556/APhysiol.100.2013.4.4

    Article  CAS  Google Scholar 

  11. McEwen BS, Nasca C, Gray JD (2016) Stress effects on neuronal structure: hippocampus, amygdala, and prefrontal cortex. Neuropsychopharmacology 41: 3–23. https://doi.org/10.1038/npp.2015.171

    Article  CAS  PubMed  Google Scholar 

  12. Ordyan NE, Pivina SG, Baranova KA, Rakitskaya VV, Akulova VK, Kholova GI (2021) Sex-dependent actions of prenatal stress on the activity of the hypothalamo-hypophyseal-adrenocortical system in rats: the role of corticosteroid receptors in the brain. Neurosci Behav Physiol 51: 357–366. https://doi.org/10.1007/s11055-021-01079-1

    Article  CAS  Google Scholar 

  13. Boos A, Kohtes J, Janssen V, Mülling C, Stelljes A, Zerbe H, Hässig M, Thole HH (2006) Pregnancy effects on distribution of progesterone receptors, oestrogen receptor alpha, glucocorticoid receptors, Ki-67 antigen and apoptosis in the bovine interplacentomal uterine wall and foetal membranes. Anim Reprod Sci 91: 55–76. https://doi.org/10.1016/j.anireprosci.2005.03.012

    Article  CAS  PubMed  Google Scholar 

  14. Solomon Z, Kotler M, Mikulincer M (1988) Combat-related posttrau-matic stress disorder among second generation Holocaust survivors: preliminary findings. Am J Psychiatry 145: 865–886. https://doi.org/10.1176/ajp.145.7.865

    Article  CAS  PubMed  Google Scholar 

  15. Yehuda R, Schmeidler J, Giller EL, Siever LJ, Binder-Brynes K (1998) Relationship between Posttraumatic stress disorder characteristics of Holocaust survivors and their adult offspring. Am J Psychiatry 155: 841–843. https://doi.org/10.1176/ajp.155.6.841

    Article  CAS  PubMed  Google Scholar 

  16. Yehuda R, Schmeidler J, Wainberg M, Binder-Brynes K, Duvdevani T (1998) Vulnerability to posttraumatic stress disorder in adult offspring of Holocaust survivors. Am J Psychiatry 155: 1163–1171. https://doi.org/10.1176/ajp.155.9.1163

    Article  CAS  PubMed  Google Scholar 

  17. Yehuda R, Bell A, Bierer LM, Schmeidler J (2008) Maternal, not paternal, PTSD is related to increased risk for PTSD in offspring of Holocaust survivors. J Psychiatr Res 42: 1104–1111. https://doi.org/10.1016/j.jpsychires.2008.01.002

    Article  PubMed  PubMed Central  Google Scholar 

  18. Cohen H, Zohar J, Gidron Y, Matar MA, Belkind D, Loewenthal U, Kozlovsky N, Kaplan Z (2006) Blunted HPA axis response to stress influences susceptibility to posttraumatic stress response in rats. Biol Psychiatry 59: 1208–1218. https://doi.org/10.1016/j.biopsych.2005.12.003

    Article  CAS  PubMed  Google Scholar 

  19. Danan D, Todder D, Zohar J, Cohen H (2021) Is PTSD-phenotype associated with HPA-axis sensitivity? Feedback inhibition and other modulating factors of glucocorticoid signaling dynamics. Int J Mol Sci 22: 6050. https://doi.org/10.3390/ijms22116050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Radley JJ, Gosselink KL, Sawchenko PE (2009) A discrete GABAergic relay mediates medial prefrontal cortical inhibition of the neuroendocrine stress response. J Neurosci 29: 7330–7340. https://doi.org/10.1523/JNEUROSCI.5924-08.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gabbott PL, Warner TA, Jays PR, Salway P, Busby SJ (2005) Prefrontal cortex in the rat: projections to subcortical autonomic, motor, and limbic centers. J Comp Neurol 492: 145–177. https://doi.org/10.1002/cne.20738

    Article  PubMed  Google Scholar 

  22. Radley JJ, Rocher AB, Rodriguez A, Ehlenberger DB, Dammann M, McEwen BS, Morrison JH, Wearne SL, Hof PR (2008) Repeated stress alters dendritic spine morphology in the rat medial prefrontal cortex. J Compar Neurol 507(1): 1141–1150. https://doi.org/10.1002/cne.21588

    Article  Google Scholar 

  23. Yehuda R, Daskalakis NP, Lehrner A, Desarnaud F, Bader HN, Makotkine I, Flory JD, Bierer LM, Meaney MJ (2014) Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring. Am J Psychiatry 171: 872–880. https://doi.org/10.1176/appi.ajp.2014.13121571

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was carried out as part of the Program “Basic Scientific Research for the Long-Term Development and Competitiveness of Society and State” (47_110_LTDaC).

Author information

Authors and Affiliations

  1. Pavlov Institute of Physiology Russian Academy Science, St. Petersburg, Russia

    N. E. Ordyan, S. G. Pivina, G. I. Kholova, V. K. Akulova & V. V. Rakitskaya

Authors
  1. N. E. Ordyan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. G. Pivina
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. G. I. Kholova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V. K. Akulova
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. V. Rakitskaya
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Idea of work and planning of the experiment—N.E.O., writing and editing the article—N.E.O., S.G.P., experimental animal preparation—G.I.K., V.K.A., data collection—V.V.R., S.G.P., G.I.K., data processing—V.K.A., G.I.K.

Corresponding author

Correspondence to N. E. Ordyan.

Ethics declarations

CONFLICT OF INTEREST

The authors declare no apparent or potential conflicts of interest related to the publication of this article.

Additional information

Translated by A. Dyomina

Russian Text © The Author(s), 2022, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2022, Vol. 108, No. 9, pp. 1114–1124https://doi.org/10.31857/S0869813922090114.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ordyan, N.E., Pivina, S.G., Kholova, G.I. et al. Differential Effect of Male Rat’s PTSD-Like or Depression-Like Status before Mating on the Activity of the Hypothalamic–Pituitary–Adrenal Axis of Adult Offspring. J Evol Biochem Phys 58, 1455–1463 (2022). https://doi.org/10.1134/S0022093022050155

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1134/S0022093022050155

Keywords:

Search

Navigation