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Dr. Robina Usman
Dr. Muhammad Omar Malik
Dr. Madiha Khattak
Dr. Syed Hamid Habib
Rifat Ullah Khan


Early life stress, late life stress, restraint stress, chronic stress, cortisol, behavioural tests.


Parental stress increases diseases in their children. In order to determine how offspring of stressed and non-stressed parents respond to chronic stress at different stages of life, a rat model was devised.130 healthy Wistar albino rats, 11 weeks of age were selected. Behavioural testing was done on all and stressed rats were removed.  Four rats were dissected for histopathology and 10 rats were sacrificed for baseline corticosterone and other hormones. The rats were divided into two groups of parent generation. One was case parents (n=70) and the other control (n=40). Parent cases were exposed to chronic unpredictable stress for three weeks. Behavioural tests were carried out to assess induction of stress in cases parents. Blood and histopathology samples were taken from 10 case parents. Rest of them were allowed to breed. Control parents were also mated at the same time. Offspring of both the groups were exposed to chronic stress, some in early life, some in late life, and some in both early and late life (all stressors for three weeks). Behavioural tests, blood for biomarkers and histology specimens were obtained after exposure to chronic stressors from all the offspring groups. Corticosterone was high in all the control offspring group compared to case offspring. Case offspring showed greater locomotion, rearing and central entries compared to control showing anxiolytic behaviour. Offspring of stressed parents were more resistant/resilient to the effects of stress as compared to the offspring of control parents.

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1. Asalgoo, S. et al. (2015) ‘Posttraumatic stress disorder (ptsd): Mechanisms and possible treatments’, Neurophysiology, 47(6), pp. 482–489.
2. Audage, N. C. and Middlebrooks, J. S. (2008) ‘The effects of childhood stress on health across the lifespan’.
3. Averill, L. A. et al. (2018) ‘Stress response modulation underlying the psychobiology of resilience’, Current Psychiatry Reports, 20, pp. 1–13.
4. Baik, J. (2020) ‘Stress and the dopaminergic reward system’, Experimental & Molecular Medicine, pp. 1879–1890. doi: 10.1038/s12276-020-00532-4.
5. Bailey, K. R. and Crawley, J. N. (2009) ‘Anxiety-related behaviors in mice.’
6. Beeton, C., Garcia, A. and Chandy, K. G. (2007) ‘Drawing blood from rats through the saphenous vein and by cardiac puncture’, Journal of Visualized Experiments, (7), pp. 1–2. doi: 10.3791/266.
7. Bick, J. et al. (2012) ‘Childhood adversity and DNA methylation of genes involved in the hypothalamus–pituitary–adrenal axis and immune system: Whole-genome and candidate-gene associations’, Development and psychopathology, 24(4), pp. 1417–1425.
8. Blunn, C. T. (1939) ‘The age of rats at sexual maturity as determined by their genetic constitution’, The Anatomical Record, 74(2), pp. 199–213.
9. Bonanno, G. A. (2004) ‘Loss, trauma, and human resilience: have we underestimated the human capacity to thrive after extremely aversive events?’, American psychologist, 59(1), p. 20.
10. Brunton, P. J. (2013) ‘Effects of maternal exposure to social stress during pregnancy: Consequences for mother and offspring’, Reproduction, 146(5). doi: 10.1530/REP-13-0258.
11. Campos, A. C. et al. (2013) ‘Animal models of anxiety disorders and stress’, Brazilian Journal of Psychiatry, 35, pp. S101–S111.
12. Cathomas, F. et al. (2019) ‘Neurobiology of resilience: interface between mind and body’, Biological psychiatry, 86(6), pp. 410–420.
13. Champagne, F. A. (2010) ‘Epigenetic influence of social experiences across the lifespan’, Developmental psychobiology, 52(4), pp. 299–311.
14. Chan, J. C., Nugent, B. M. and Bale, T. L. (2018) ‘Parental advisory: maternal and paternal stress can impact offspring neurodevelopment’, Biological psychiatry, 83(10), pp. 886–894.
15. Chen, R. et al. (2021) ‘Chronic circadian phase advance in male mice induces depressive-like responses and suppresses neuroimmune activation’, Brain, Behavior, & Immunity-Health, 17, p. 100337.
16. Christoffel, D. J., Golden, S. A. and Russo, S. J. (2011) ‘Structural and synaptic plasticity in stress-related disorders’.
17. Chu, B. et al. (2021) ‘Physiology, stress reaction’, in StatPearls [Internet]. StatPearls Publishing.
18. Cicchetti, D. and Rogosch, F. A. (2007) ‘Personality, adrenal steroid hormones, and resilience in maltreated children: A multilevel perspective’, Development and psychopathology, 19(3), pp. 787–809.
19. Coffman, J. A. (2020) ‘Chronic stress, physiological adaptation and developmental programming of the neuroendocrine stress system’, Future Neurology, 15(1). doi: 10.2217/fnl-2019-0014.
20. Dal-Zotto, S., Martı́, O. and Armario, A. (2000) ‘Influence of single or repeated experience of rats with forced swimming on behavioural and physiological responses to the stressor’, Behavioural brain research, 114(1–2), pp. 175–181.
21. Davis, E. P. et al. (2011) ‘Prenatal maternal stress programs infant stress regulation’, Journal of Child Psychology and Psychiatry, 52(2), pp. 119–129.
22. Dickson, D. A. et al. (2018) ‘Reduced levels of miRNAs 449 and 34 in sperm of mice and men exposed to early life stress’, Translational Psychiatry, 8(1), p. 101.
23. Espejo, E. P. et al. (2007) ‘Stress sensitization and adolescent depressive severity as a function of childhood adversity: a link to anxiety disorders’, Journal of abnormal child psychology, 35, pp. 287–299.
24. Feder, A., Nestler, E. J. and Charney, D. S. (2009) ‘Psychobiology and molecular genetics of resilience’, Nature Reviews Neuroscience, 10(6), pp. 446–457.
25. Glover, V. (2015) ‘Prenatal stress and its effects on the fetus and the child: possible underlying biological mechanisms’, Perinatal programming of neurodevelopment, pp. 269–283.
26. Grissom, N. and Bhatnagar, S. (2009) ‘Habituation to repeated stress: get used to it’, Neurobiology of learning and memory, 92(2), pp. 215–224.
27. Gur, T. L. et al. (2017) ‘Prenatal stress affects placental cytokines and neurotrophins, commensal microbes, and anxiety-like behavior in adult female offspring’, Brain, behavior, and immunity, 64, pp. 50–58.
28. Gutteling, B. M., de Weerth, C. and Buitelaar, J. K. (2005) ‘Prenatal stress and children’s cortisol reaction to the first day of school’, Psychoneuroendocrinology, 30(6), pp. 541–549.
29. Herman, J. P. (2013) ‘Neural control of chronic stress adaptation’, Frontiers in behavioral neuroscience, 7, p. 61.
30. Juster, R.-P., McEwen, B. S. and Lupien, S. J. (2010) ‘Allostatic load biomarkers of chronic stress and impact on health and cognition’, Neuroscience & Biobehavioral Reviews, 35(1), pp. 2–16.
31. Kallai, J. et al. (2007) ‘Cognitive and affective aspects of thigmotaxis strategy in humans.’, Behavioral neuroscience, 121(1), p. 21.
32. Kemeny, M. E. (2003) ‘The psychobiology of stress’, Current directions in psychological science, 12(4), pp. 124–129.
33. Koolhass, J. M., Bartolomucci, A. and Buwalda, B. (2011) ‘Stress revisited: a critical evaluation of the stress concept’, Neuroscience and Biobehavioral Reviews, 35(5), pp. 1291–1301.
34. Ladd, C. O. et al. (2004) ‘Long-term adaptations in glucocorticoid receptor and mineralocorticoid receptor mRNA and negative feedback on the hypothalamo-pituitary-adrenal axis following neonatal maternal separation’, Biological psychiatry, 55(4), pp. 367–375.
35. Luthar, S. S. (2015) ‘Resilience in development: A synthesis of research across five decades’, Developmental psychopathology: Volume three: Risk, disorder, and adaptation, pp. 739–795.
36. MacDonald, D. and Wetherell, M. A. (2019) ‘Competition stress leads to a blunting of the cortisol awakening response in elite rowers’, Frontiers in Psychology, 10(JULY). doi: 10.3389/fpsyg.2019.01684.
37. Makori Arika, W. et al. (2019) ‘Effects of DCM leaf Extract of Gnidia glauca (Fresen) on Locomotor Activity, Anxiety and Exploration-Like Behaviors in High Fat Diet-Induced Obese Rats’, bioRxiv, p. 786103.
38. Mariotti, A. (2015) ‘The effects of chronic stress on health: new insights into the molecular mechanisms of brain–body communication’, Future science OA, 1(3).
39. Martin, P. and Martin, M. (2002) ‘Proximal and distal influences on development: The model of developmental adaptation’, Developmental Review, 22(1), pp. 78–96.
40. Mifsud, K. R. and Reul, J. M. H. M. (2018) ‘Mineralocorticoid and glucocorticoid receptor-mediated control of genomic responses to stress in the brain’, Stress, 21(5), pp. 389–402.
41. MN, S. (2012) ‘Sternberg EM. Glucocorticoid regulation of inflammation and its functional correlates: from HPA axis to glucocorticoid receptor dysfunction’, Ann. NY Acad. Sci, 1261, pp. 55–63.
42. Moisiadis, V. G. and Matthews, S. G. (2014) ‘Glucocorticoids and fetal programming part 1: outcomes’, Nature Reviews Endocrinology, 10(7), pp. 391–402.
43. Ohl, F. (2003) ‘Testing for anxiety’, Clinical Neuroscience Research, 3(4–5), pp. 233–238.
44. Osório, C. et al. (2017) ‘Adapting to stress: understanding the neurobiology of resilience’, Behavioral Medicine, 43(4), pp. 307–322.
45. Patki, G. et al. (2015) ‘Tempol treatment reduces anxiety-like behaviors induced by multiple anxiogenic drugs in rats’, PloS one, 10(3), p. e0117498.
46. Pearlin, L. I. et al. (1981) ‘The stress process’, Journal of Health and Social behavior, pp. 337–356.
47. Pfau, M. L. and Russo, S. J. (2015) ‘Peripheral and central mechanisms of stress resilience’, Neurobiology of stress, 1, pp. 66–79.
48. Radahmadi, M. et al. (2017) ‘Stress biomarker responses to different protocols of forced exercise in chronically stressed rats’, Journal of bodywork and movement therapies, 21(1), pp. 63–68.
49. Ramos, A. et al. (2008) ‘Integrating the open field, elevated plus maze and light/dark box to assess different types of emotional behaviors in one single trial’, Behavioural brain research, 193(2), pp. 277–288.
50. Risling, T. E., Caulkett, N. A. and Florence, D. (2012) ‘Open-drop anesthesia for small laboratory animals’, The Canadian Veterinary Journal, 53(3), p. 299.
51. Schmatz, R. et al. (2009) ‘Resveratrol prevents memory deficits and the increase in acetylcholinesterase activity in streptozotocin-induced diabetic rats’, European Journal of Pharmacology, 610(1–3), pp. 42–48. doi: 10.1016/j.ejphar.2009.03.032.
52. Seibenhener, M. L. and Wooten, M. C. (2015) ‘Use of the open field maze to measure locomotor and anxiety-like behavior in mice’, Journal of visualized experiments: JoVE, (96).
53. St-Cyr, S. et al. (2017) ‘Maternal programming of sex-specific responses to predator odor stress in adult rats’, Hormones and behavior, 94, pp. 1–12.
54. Stamford, J. A. et al. (1991) ‘Voltammetric evidence that subsensitivity to reward following chronic mild stress is associated with increased release of mesolimbic dopamine’, Psychopharmacology, 105, pp. 275–282.
55. Swaminathan, A. et al. (2023) ‘Stress resilience is established during development and is regulated by complement factors’, Cell Reports, 42(1), p. 111973.
56. Vagnerová, K. et al. (2023) ‘Profiling of adrenal corticosteroids in blood and local tissues of mice during chronic stress’, Scientific Reports, 13(1), pp. 1–11. doi: 10.1038/s41598-023-34395-2.
57. Wachs, T. D. (1992) The nature of nurture. Sage publications.
58. Wu, G. et al. (2013) ‘Understanding resilience’, Frontiers in behavioral neuroscience, 7, p. 10.
59. Wyman, P. A. et al. (1991) ‘Developmental and family milieu correlates of resilience in urban children who have experienced major life stress’, American Journal of community psychology, 19(3), p. 405.
60. Yehuda, R. et al. (2006) ‘Clinical correlates of DHEA associated with post‐traumatic stress disorder’, Acta Psychiatrica Scandinavica, 114(3), pp. 187–193.