Startseite Evidence of alterations in the learning and memory in offspring of stress-induced male rats
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Evidence of alterations in the learning and memory in offspring of stress-induced male rats

  • Ashok Kumar Jyothi , Balaji Thotakura EMAIL logo , Swathi Priyadarshini C , Manickam Subramanian und Hannah Sugirthabai Rajila
Veröffentlicht/Copyright: 22. Juni 2021
Journal of Basic and Clinical Physiology and Pharmacology
Aus der Zeitschrift Journal of Basic and Clinical Physiology and Pharmacology Band 34 Heft 4

Abstract

Objectives

There is extensive data pointing to offspring outcomes related to maternal life incidents, but there is less research concerning the association between paternal life events and progeny brain development and behaviour. As male gametogenesis is a continuous process, the incidences happening in life can modify the epigenetic regulation, altering the offspring’s development and behaviour. The present study evaluates the effects of paternal stress during different life periods on their offspring’s learning ability, memory, morphological and biochemical changes in the prefrontal cortex and hippocampus in the rat model.

Methods

Four weeks’ old male rats were subjected to five variable stressors at the rate of one per day. Stress received male rats were bred with naive female rats for 1 to 3 nights. The offspring’s learning and memory were assessed by the Morris water maze test and automated Y maze. Following behavioural studies, offspring were euthanized to examine global DNA methylation, neurotransmitter levels, namely acetylcholine, glutamate in the hippocampus and frontal cortex.

Results

The offspring of stress-induced animals exhibited a delay in acquiring learning and defect in memory and altered global DNA methylation in the hippocampus (p=0.000124). There was significant reduction of acetylcholine and glutamate levels in hippocampus (p=0.000018, p=0.00001, respectively) and in prefrontal cortex (p=0.00001, p=0.00001, respectively). HPA axis of offspring was altered considerably (p=0.00001). The histomorphometry of the prefrontal cortex and different hippocampal regions revealed a statistically significant (p<0.05) reduction in neuronal numbers in the offspring of stressed animals compared to that of control. These impacts were markedly high in the offspring of fathers who received stress during both pubertal and adult periods.

Conclusions

The findings of this study demonstrate that paternal stress can impact offspring learning and memory.

Keywords: DNA methylation; HPA axis; learning; memory; offspring; paternal stress
Corresponding author: Balaji Thotakura, Professor, Department of Anatomy, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Chettinad Health City, Kanchipuram, Tamil Nadu, India, Phone: +91 9710905221, E-mail:

  1. Research funding: This work is financially supported by the Chettinad Academy of Research and Education, Kelambakkam, Chennai, India.

  2. Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.

  3. Competing interest: Authors state no conflict of interest.

  4. Informed consent: Not applicable.

  5. Ethical approval: Animal experiments were conducted according to the guidelines of the Committee for the Purpose of Control and Supervision of Experiments on Animals (CPCSEA). The experimental protocol was approved by the Institutional Animal Ethics Committee of Chettinad Hospital and Research Institute (Approval number: IAEC 1/Desp.No.7/Dt.02.03.17).

References

1. Lupien, SJ, McEwen, BS, Gunnar, MR, Heim, C. Effects of stress throughout the lifespan on the brain, behaviour and cognition. Nat Rev Neurosci 2009;10:434–45. https://doi.org/10.1038/nrn2639.Suche in Google Scholar PubMed

2. Lupien, SJ, Maheu, F, Tu, M, Fiocco, A, Schramek, TE. The effects of stress and stress hormones on human cognition: implications for the field of brain and cognition. Brain Cognit 2007;65:209–37. https://doi.org/10.1016/j.bandc.2007.02.007.Suche in Google Scholar PubMed

3. Finsterwald, C, Alberini, CM. Stress and glucocorticoid receptor-dependent mechanisms in long-term memory: from adaptive responses to psychopathologies. Neurobiol Learn Mem 2014;112:17–29. https://doi.org/10.1016/j.nlm.2013.09.017.Suche in Google Scholar PubMed PubMed Central

4. Darcet, F, Mendez-David, I, Tritschler, L, Gardier, AM, Guilloux, JP, David, DJ. Learning and memory impairments in a neuroendocrine mouse model of anxiety/depression. Front Behav Neurosci 2014;8:136. https://doi.org/10.3389/fnbeh.2014.00136.Suche in Google Scholar PubMed PubMed Central

5. Maccari, S, Krugers, HJ, Morley‐Fletcher, S, Szyf, M, Brunton, PJ. The consequences of early‐life adversity: neurobiological, behavioural and epigenetic adaptations. J Neuroendocrinol 2014;26:707–23. https://doi.org/10.1111/jne.12175.Suche in Google Scholar PubMed

6. Weinstock, M. The long-term behavioural consequences of prenatal stress. Neurosci Biobehav Rev 2008;32:1073–86. https://doi.org/10.1016/j.neubiorev.2008.03.002.Suche in Google Scholar PubMed

7. Susser, E, Hoek, HW, Brown, A. Neurodevelopmental disorders after prenatal famine: the story of the Dutch Famine Study. Am J Epidemiol 1998;147:213–6. https://doi.org/10.1093/oxfordjournals.aje.a009439.Suche in Google Scholar PubMed

8. Olegård, R, Sabel, KG, Aronsson, M, Sandin, B, Johansson, PR, Carlsson, C, et al.. Effects on the child of alcohol abuse during pregnancy: retrospective and prospective studies. Acta Paediatr 1979;68:112–21. https://doi.org/10.1111/j.1651-2227.1979.tb06170.x.Suche in Google Scholar PubMed

9. Williams, JH, Ross, L. Consequences of prenatal toxin exposure for mental health in children and adolescents. Eur Child Adolesc Psychiatry 2007;16:243–53. https://doi.org/10.1007/s00787-006-0596-6.Suche in Google Scholar PubMed

10. Saavedra-Rodríguez, L, Feig, LA. Chronic social instability induces anxiety and defective social interactions across generations. Biol Psychiatry 2013;73:44–53. https://doi.org/10.1016/j.biopsych.2012.06.035.Suche in Google Scholar PubMed PubMed Central

11. Bohacek, J, Farinelli, M, Mirante, O, Steiner, G, Gapp, K, Coiret, G, et al.. Pathological brain plasticity and cognition in the offspring of males subjected to postnatal traumatic stress. Molecular Psychiatry 2015;20:621–31. https://doi.org/10.1038/mp.2014.80.Suche in Google Scholar PubMed

12. Bale, TL. Epigenetic and transgenerational reprogramming of brain development. Nat Rev Neurosci 2015;16:332–44. https://doi.org/10.1038/nrn3818.Suche in Google Scholar PubMed PubMed Central

13. Skinner, MK. Environmental stress and epigenetic transgenerational inheritance. BMC Med 2014;12:153. https://doi.org/10.1186/s12916-014-0153-y.Suche in Google Scholar PubMed PubMed Central

14. Szyf, M. Nongenetic inheritance and transgenerational epigenetics. Trends Mol Med 2015;21:134–44. https://doi.org/10.1016/j.molmed.2014.12.004.Suche in Google Scholar PubMed

15. Toth, M. Mechanisms of non-genetic inheritance and psychiatric disorders. Neuropsychopharmacology 2015;40:129–40. https://doi.org/10.1038/npp.2014.127.Suche in Google Scholar PubMed PubMed Central

16. Kinney, DK, Munir, KM, Crowley, DJ, Miller, AM. Prenatal stress and risk for autism. Neurosci Biobehav Rev. 2008;32:1519–32. https://doi.org/10.1016/j.neubiorev.2008.06.004.Suche in Google Scholar PubMed PubMed Central

17. Rosenfield, PJ, Kleinhaus, K, Opler, M, Perrin, M, Learned, N, Goetz, R, et al.. Later paternal age and sex differences in schizophrenia symptoms. Schizophr Res 2010;116:191–5. https://doi.org/10.1016/j.schres.2009.10.020.Suche in Google Scholar PubMed PubMed Central

18. Short, AK, Fennell, KA, Perreau, VM, Fox, A, O’Bryan, MK, Kim, JH, et al.. Elevated paternal glucocorticoid exposure alters the small noncoding RNA profile in sperm and modifies anxiety and depressive phenotypes in the offspring. Transl Psychiatry 2016;6:e837. https://doi.org/10.1038/tp.2016.109.Suche in Google Scholar PubMed PubMed Central

19. Dietz, DM, LaPlant, Q, Watts, EL, Hodes, GE, Russo, SJ, Feng, J, et al.. Paternal transmission of stress-induced pathologies. Biological Psychiatry 2011;70:408–14. https://doi.org/10.1016/j.biopsych.2011.05.005.Suche in Google Scholar PubMed PubMed Central

20. Matthews, SG. Early programming of the hypothalamo–pituitary–adrenal axis. Trends Endocrinol Metabol 2002;13:373–80. https://doi.org/10.1016/s1043-2760(02)00690-2.Suche in Google Scholar PubMed

21. Rosenheck, R. Impact of posttraumatic stress disorder of World War II on the next generation. J Nerv Ment Dis 1986;174:319–27. https://doi.org/10.1097/00005053-198606000-00001.10.1097/00005053-198606000-00001Suche in Google Scholar

22. Yehuda, R, Daskalakis, NP, Lehrner, A, Desarnaud, F, Bader, HN, Makotkine, I, et al.. Influences of maternal and paternal PTSD on epigenetic regulation of the glucocorticoid receptor gene in Holocaust survivor offspring. American Journal of Psychiatry 2014;171:872–80. https://doi.org/10.1176/appi.ajp.2014.13121571.Suche in Google Scholar PubMed PubMed Central

23. Yehuda, R, Halligan, SL, Bierer, LM. Relationship of parental trauma exposure and PTSD to PTSD, depressive and anxiety disorders in offspring. J Psychiatr Res 2001;35:261–70. https://doi.org/10.1016/s0022-3956(01)00032-2.Suche in Google Scholar PubMed

24. Yehuda, R, Bierer, LM. Transgenerational transmission of cortisol and PTSD risk. Prog Brain Res 2007;167:121–35. https://doi.org/10.1016/s0079-6123(07)67009-5.Suche in Google Scholar PubMed

25. Rodgers, AB, Morgan, CP, Bronson, SL, Revello, S, Bale, TL. Paternal stress exposure alters sperm microRNA content and reprograms offspring HPA stress axis regulation. J Neurosci 2013;33:9003–12. https://doi.org/10.1523/jneurosci.0914-13.2013.Suche in Google Scholar PubMed PubMed Central

26. Yeshurun, S, Short, AK, Bredy, TW, Pang, TY, Hannan, AJ. Paternal environmental enrichment transgenerationally alters affective behavioral and neuroendocrine phenotypes. Psychoneuroendocrinology 2017;77:225–35. https://doi.org/10.1016/j.psyneuen.2016.11.013.Suche in Google Scholar PubMed

27. Champagne, FA. Epigenetic influence of social experiences across the lifespan. Dev Psychobiol 2010;52:299–311. https://doi.org/10.1002/dev.20436.Suche in Google Scholar PubMed

28. Franklin, TB, Russig, H, Weiss, IC, Gräff, J, Linder, N, Michalon, A, et al.. Epigenetic transmission of the impact of early stress across generations. Biol Psychiatry 2010;68:408–15. https://doi.org/10.1016/j.biopsych.2010.05.036.Suche in Google Scholar PubMed

29. Crews, D, Gillette, R, Scarpino, SV, Manikkam, M, Savenkova, MI, Skinner, MK. Epigenetic transgenerational inheritance of altered stress responses. Proc Natl Acad Sci USA 2012;109:9143–8. https://doi.org/10.1073/pnas.1118514109.Suche in Google Scholar PubMed PubMed Central

30. Agranoff, BW, Cotman, CW, Uhler, MD. Learning and memory. Basic Neurochem 1999:1027–52.Suche in Google Scholar

31. Morris, R Developments of a water-maze procedure for studying spatial learning in the rat. J Neurosci Methods 1984;11:47–60. https://doi.org/10.1016/0165-0270(84)90007-4.Suche in Google Scholar PubMed

32. Ru, M, Liu, H. Association between Y-Maze acquisition learning and major histocompatibility complex class II polymorphisms in mice. BioMed Res Int 2018;19:6381932. https://doi.org/10.1155/2018/6381932.10.1155/2018/6381932Suche in Google Scholar

33. Chan, JC, Nugent, BM, Bale, TL. Parental advisory: maternal and paternal stress can impact offspring neurodevelopment. Biol Psychiatry 2018;83:886–94. https://doi.org/10.1016/j.biopsych.2017.10.005.Suche in Google Scholar PubMed PubMed Central

34. Griffin, J. Methods of sperm DNA extraction for genetic and epigenetic studies. InSpermatogenesis. Totowa, NJ: Humana Press; 2013:379–84 pp.10.1007/978-1-62703-038-0_32Suche in Google Scholar

35. Gao, J, Wang, H, Liu, Y, Li, YY, Chen, C, Liu, LM, et al.. Glutamate and GABA imbalance promotes neuronal apoptosis in hippocampus after stress. Med Sci Mon Int Med J Exp Clin Res 2014;20:499. https://doi.org/10.12659/MSM.890589.Suche in Google Scholar PubMed PubMed Central

36. Onaolapo, OJ, Onaolapo, AY, Akanmu, MA, Gbola, O. Evidence of alterations in brain structure and antioxidant status following ‘low-dose’monosodium glutamate ingestion. Pathophysiology 2016;23:147–56.https://doi.org/10.1016/j.pathophys.2016.05.001.Suche in Google Scholar PubMed

37. Hilton, KJ, Cunningham, C, Reynolds, RA, Perry, VH. Early hippocampal synaptic loss precedes neuronal loss and associates with early behavioural deficits in three distinct strains of prion disease. PLoS One 2013;8:e68062. https://doi.org/10.1371/journal.pone.0068062.Suche in Google Scholar PubMed PubMed Central

38. Hain, AM. Increase in weight of the mother and of the foetus during pregnancy (rat). Q J Exp Physiol: Translation and Integration. 1932;22:71–8 https://doi.org/10.1113/expphysiol.1932.sp000560.Suche in Google Scholar

39. Corvino, SB, Volpato, GT, Macedo, NC, Sinzato, YK, Rudge, MV, Damasceno, DC. Physiological and biochemical measurements before, during and after pregnancy of healthy rats. Acta Cir Bras 2015;30:668–74. https://doi.org/10.1590/s0102-865020150100000003.Suche in Google Scholar PubMed

40. Weiss, IC, Franklin, TB, Vizi, S, Mansuy, IM. Inheritable effect of unpredictable maternal separation on behavioral responses in mice. Front Behav Neurosci 2011;5:3. https://doi.org/10.3389/fnbeh.2011.00003.Suche in Google Scholar PubMed PubMed Central

41. Yao, Y, Robinson, AM, Zucchi, FC, Robbins, JC, Babenko, O, Kovalchuk, O, et al.. Ancestral exposure to stress epigenetically programs preterm birth risk and adverse maternal and newborn outcomes. BMC Med 2014;12:121. https://doi.org/10.1186/s12916-014-0121-6.Suche in Google Scholar PubMed PubMed Central

42. Kumar, JA, Balaji, T, Priyadarshini, CS, Subramanian, M, Sundaramurthi, I. Non concurrent multimodal stress decreases sperm quality and motor activity in male Wister albino rats. Biomed Pharmacol J 2019;12:1505–17. https://doi.org/10.13005/bpj/1781.Suche in Google Scholar

43. Anderson, RE, Hanson, HA, Thai, D, Zhang, C, Presson, AP, Aston, KI, et al.. Do paternal semen parameters influence the birth weight or BMI of the offspring? A study from the Utah Population Database. J Assist Reprod Genet 2018;35:793–9. https://doi.org/10.1007/s10815-018-1154-0.Suche in Google Scholar PubMed PubMed Central

44. Franklin, TB, Linder, N, Russig, H, Thöny, B, Mansuy, IM. Influence of early stress on social abilities and serotonergic functions across generations in mice. PLoS One 2011;6:e21842. https://doi.org/10.1371/journal.pone.0021842.Suche in Google Scholar PubMed PubMed Central

45. Jirtle, RL, Skinner, MK. Environmental epigenomics and disease susceptibility. Nat Rev Genet. 2007;8:253–62.https://doi.org/10.1038/nrg2045.Suche in Google Scholar PubMed PubMed Central

46. Bird, A Perceptions of epigenetics. Nature 2007;447:396. https://doi.org/10.1038/nature05913.Suche in Google Scholar PubMed

47. Mychasiuk, R, Ilnytskyy, S, Kovalchuk, O, Kolb, B, Gibb, R. Intensity matters: brain, behaviour and the epigenome of prenatally stressed rats. Neuroscience 2011;180:105–10. https://doi.org/10.1016/j.neuroscience.2011.02.026.Suche in Google Scholar PubMed

48. Kempermann, G, Gast, D, Gage, FH. Neuroplasticity in old age: sustained fivefold induction of hippocampal neurogenesis by long‐term environmental enrichment. Ann Neurol 2002;52:135–43. https://doi.org/10.1002/ana.10262.Suche in Google Scholar PubMed

49. Arai, JA, Feig, LA. Long-lasting and transgenerational effects of an environmental enrichment on memory formation. Brain Res Bull. 2011;85:30–5. https://doi.org/10.1016/j.brainresbull.2010.11.003.Suche in Google Scholar PubMed PubMed Central

50. Kiyono, S, Seo, ML, Shibagaki, M, Inouye, M. Facilitative effects of maternal environmental enrichment on maze learning in rat offspring. Physiol Behav 1985;34:431–5. https://doi.org/10.1016/0031-9384(85)90207-0.Suche in Google Scholar PubMed

51. McEntee, WJ, Crook, TH. Glutamate: its role in learning, memory, and the aging brain. Psychopharmacology 1993;111:391–401. https://doi.org/10.1007/bf02253527.Suche in Google Scholar

52. Okubo, Y, Sekiya, H, Namiki, S, Sakamoto, H, Iinuma, S, Yamasaki, M, et al.. Imaging extrasynaptic glutamate dynamics in the brain. Neurosci Res 2009:S142–3.10.1016/j.neures.2009.09.713Suche in Google Scholar

53. Crow, TJ, Grove-White, IG. An analysis of the learning deficit following hyoscine administration to man. Br J Pharmacol. 1973;49:322. https://doi.org/10.1111/j.1476-5381.1973.tb08379.x.Suche in Google Scholar PubMed PubMed Central

54. Ridley, RM, Murray, TK, Johnson, JA, Baker, HF. Learning impairment following lesion of the basal nucleus of Meynert in the marmoset: modification by cholinergic drugs. Brain Res 1986;376:108–16. https://doi.org/10.1016/0006-8993(86)90904-2.Suche in Google Scholar PubMed

55. Easton, A, Ridley, RM, Baker, HF, Gaffan, D. Unilateral lesions of the cholinergic basal forebrain and fornix in one hemisphere and inferior temporal cortex in the opposite hemisphere produce severe learning impairments in rhesus monkeys. Cerebr Cortex 2002;12:729–36. https://doi.org/10.1093/cercor/12.7.729.Suche in Google Scholar PubMed

56. y Cajal, SR. Degeneration & regeneration of the nervous system. Hafner Publishing Company; 1959.Suche in Google Scholar

57. European College of Neuropsychopharmacology. Neurogenesis in adult brain: association with stress and depression. ScienceDaily. Available from: www.sciencedaily.com/releases/2008/08/080831114717.htm [Accessed 4 Aug 2019].Suche in Google Scholar

58. Altman, J Autoradiographic investigation of cell proliferation in the brains of rats and cats. Anat Rec 1963;145:573–91. https://doi.org/10.1002/ar.1091450409.Suche in Google Scholar PubMed

59. Altman, J, Das, GD. Autoradiographic and histological evidence of postnatal hippocampal neurogenesis in rats. J Comp Neurol 1965;124:319–35.https://doi.org/10.1002/cne.901240303.Suche in Google Scholar PubMed

60. Stuchlik, A. Dynamic learning and memory, synaptic plasticity and neurogenesis: an update. Front Behav Neurosci 2014;8:106.https://doi.org/10.3389/fnbeh.2014.00106.Suche in Google Scholar PubMed PubMed Central

Received: 2020-07-06
Accepted: 2021-04-20
Published Online: 2021-06-22

© 2021 Walter de Gruyter GmbH, Berlin/Boston

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  2. Minireview
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https://doi.org/10.1515/jbcpp-2020-0183
Schlagwörter für diesen Artikel
DNA methylation; HPA axis; learning; memory; offspring; paternal stress

Artikel in diesem Heft

  1. Frontmatter
  2. Minireview
  3. Impact of mental toughness on athlete’s performance and interventions to improve
  4. Reviews
  5. A review of the mechanisms of anti-cancer activities of some medicinal plants–biochemical perspectives
  6. Antimicrobials in COVID-19: strategies for treating a COVID-19 pandemic
  7. Anxiolytic effects of vestibular stimulation: an update
  8. Original Articles
  9. Intermittent exposure to green and white light-at-night activates hepatic glycogenolytic and gluconeogenetic activities in male Wistar rats
  10. Study of pre-operative neutrophil–lymphocyte ratio in urothelial carcinoma
  11. The effects of Berberis vulgaris L. root extract on the opiate withdrawal syndrome and psychological factors: a randomized double-blind clinical trial
  12. Evidence of alterations in the learning and memory in offspring of stress-induced male rats
  13. The impact of vestibular symptoms and electronystagmography results on recovery from sudden sensorineural hearing loss
  14. Complementary mechanisms of modulation of spontaneous phasic contractions by the gaseous signalling molecules NO, H2S, HNO and the polysulfide Na2S3 in the rat colon
  15. Pharmacist-directed Sputnik V (GAM-COVID-VAC) surveillance program: a prospective observational study in Southern India
  16. Correlation among Poincare plot and traditional heart rate variability indices in adults with different risk levels of metabolic syndrome: a cross-sectional approach from Southern India
  17. Does etodolac affect TRPA1 functionality in vivo in human?
  18. Dynamic of irisin secretion change after moderate-intensity chronic physical exercise on obese female
  19. Letter to the Editor
  20. The prospective record-breaking obesity drug tirzepatide raises concerns about affordability
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