Year 2021, Volume 7 , Issue 4, Pages 340 - 347 2021-07-04

Prenatal stress impairs recognition memory and leads to neurodevelopmental deficits in hippocampus of adolescent rats with early acute pentylenetetrazole-kindling

Kübra ÇELİK [1] , Petek BİLİM [2] , Gurur GARİP [3] , Burak DURMAZ [4] , Eser Y. SÖZMEN [5] , Meral BAKA [6]


Objectives: This study aimed to investigate the effects of prenatal stress (PS) on hippocampus of early acute pentylenetetrazole (PTZ)-kindled offspring in adolescence. Recognition memory, morphological changes and synaptophysin levels in hippocampus were evaluated.

Methods: Restraint stress was induced to a group of pregnant dams and non-stressed (NA) group remained undisturbed. Next, male and female offspring were divided as 1. PS-PTZ, 2. PS -control, 3. NA-PTZ and 4. NA-control (n = 12 in each group). The object recognition test was performed following PTZ injection (45 mg/kg) on postnatal day 10 (P10). Brains were collected on postnatal day 35 (P35) to determine neuronal density and synaptophysin expression by immuno/-histological studies. Further, oxidative stress products in hippocampus were analyzed with different biochemical assays.

Results: PS impaired recognition memory in PTZ group significantly (p = 0.03); however, the impairment of PS was reversible in control group compared to PTZ (p = 0.04). Furthermore, PS caused neuronal loss in CA1 (p = 0.01) and decreased synaptophysin expression in the CA3 area of hippocampus in PTZ group (p = 0.03). PS also increased the oxidative stress markers in PTZ group significantly (p < 0.05).

Conclusions: These results suggest that PS causes neurodevelopmental deficits in adolescent hippocampus and recognition memory after early-life seizures prominently. However, the damage of only PS in adolescence can be reversible. Therefore, the effects of PS in the adult hippocampus and other regions of brain need to be further studied.

prenatal stress, hippocampus, PTZ-kindling, seizure, recognition memory
  • 1. Weinstock M. The long-term behavioural consequences of prenatal stress. Neurosci Biobehav Rev 2008;32:1073-86.
  • 2. Qulu L, Daniels WM, Mabandla M. Exposure to prenatal stress enhances the development of seizures in young rats. Metab Brain Dis 2012;27:399-404.
  • 3. Lopim GM, Gutierre RC, da Silva, EA, Arida RM. Physical exercise during pregnancy minimizes PTZ-induced behavioral manifestations in prenatally stressed offspring. Dev Psychobiol 2020;62:240-49.
  • 4. Krugers HJ, Karst H, Joels M. Interactions between noradrenaline and corticosteroids in the brain: from electrical activity to cognitive performance. Front Cell Neurosci 2012;6:15.
  • 5. Weinstock M. The potential influence of maternal stress hormones on development and mental health of the offspring. Brain Behav Immun 2005;19:296-308.
  • 6. Jia N, Yang K, Sun Q, Cai Q, Li H, Cheng D, et al. Prenatal stress causes dendritic atrophy of pyramidal neurons in hippocampal CA3 region by glutamate in offspring rats. Dev Neurobiol 2010;70:114-25.
  • 7. Lai MC, Huang LT. Effects of early life stress on neuroendocrine and neurobehavior: mechanisms and implications. Pediatr Neonatol 2011;52:122-9.
  • 8. Schoenfeld TJ, McCausland HC, Morris HD, Padmanaban V, Cameron HA. Stress and loss of adult neurogenesis differentially reduce hippocampal volume. Biol Psychiatry 2017;82:914-23.
  • 9. Fujioka T, Fujioka A, Tan N, Chowdhury GMI, Mouri H, Sakata Y, et.al. Mild prenatal stress enhances learning performance in the non-adopted rat offspring. Neuroscience 2001;103:301-7.
  • 10. Cannizzaro C, Plescia F, Martire M, Gagliano M, Cannizzaro G, Mantia G, et. al. Single, intense prenatal stress decreases emotionality and enhances learning performance in the adolescent rat offspring: Interaction with a brief, daily maternal separation. Behav. Brain Res 2006;169:128-36.
  • 11. Zhu Z, Li X, Chen W, Zhao Y, Li H, Qing C, et. al. Prenatal stress causes gender-dependent neuronal loss and oxidative stress in rat hippocampus. J. Neurosci Res 2004;78:837-44.
  • 12. Ikonomidou C, Kaindl AM. Neuronal death and oxidative stress in the developing brain. Antioxidants Redox Signal 2011;14:1535-50.
  • 13. Tannenberg RK, Dodd PR. Cell Damage/excitotoxicity. excitotoxicity and neurodegenerative disease, in: Encyclopedia of Basic Epilepsy Research. Elsevier, 2009: pp.114-9.
  • 14. Andersen P, Morris R, Amaral D, O’Keefe J, Bliss T, The hippocampus book. Oxford University Press 2007.
  • 15. Edwards H, Dortok D, Tam J, Won D, Burnham WM. Prenatal stress alters seizure thresholds and the development of kindled seizures in infant and adult rats. Horm Behav 2002;42:437-47.
  • 16. Nassiri-Asl M, Shariati-Rad S, Zamansoltani F. Anticonvulsive effects of intracerebroventricular administration of rutin in rats. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:989-93.
  • 17. Ennaceur A, Delacour J. A new one-trial test for neurobiological studies of memory in rats. 1: Behavioral data. Behav. Brain Res 1988;31:47-59.
  • 18. Turgut M, Uyanıkgil Y, Ateş U, Baka M, Yurtseven ME. Pinealectomy stimulates and exogenous melatonin inhibits harmful effects of epileptiform activity during pregnancy in the hippocampus of newborn rats: an immunohistochemical study. Childs Nerv Syst 2006;22:481-8.
  • 19. Sözmen YE, Sözmen B, Girgin FK, Delen Y, Azarsiz E, Erdener D, et.al. Antioxidant enzymes and paraoxonase show a co-activity in preserving low-density lipoprotein from oxidation. Clin Exp Med 2001;1:195-9.
  • 20. Aebi H. Catalase in vitro. Methods Enzymol 1984;105:121-6.
  • 21. Grisham MB, Anzueto Hernandez L, Granger DN. Xanthine oxidase and neutrophil infiltration in intestinal ischemia. Am J Physiol 1986;251(4 Pt 1):G567-74.
  • 22. Sawyer NT, Escayg A. Stress and epilepsy: multiple models, multiple outcomes. J Clin Neurophysiol 2010;27:445-52.
  • 23. Ahmadi M, Dufour JP, Seifritz E, Mirnajafi-Zadeh J, Saab BJ. The PTZ kindling mouse model of epilepsy exhibits exploratory drive deficits and aberrant activity amongst VTA dopamine neurons in both familiar and novel space. Behav Brain Res 2017;330:1-7.
  • 24. Sanchez R, Dai W, Levada R, Lippman JJ, Jensen FE. AMPA/kainate receptor-mediated downregulation of GABAergic synaptic transmission by calcineurin after seizures in the developing rat brain. J Neurosci 2005;25:3442-51.
  • 25. Barker GRI, Warburton EC. When is the hippocampus involved in recognition memory? J Neurosci 2011;31:10721-31.
  • 26. Broadbent NJ, Gaskin S, Squire LR, Clark RE. Object recognition memory and the rodent hippocampus. Learn Mem 2010;17:5-11.
  • 27. Detour J, Schroeder H, Desor D, Nehlig A. 5-month period of epilepsy impairs spatial memory, decreases anxiety, but spares object recognition in the lithium-pilocarpine model in adult rats. Epilepsia 2005;46:499-508.
  • 28. Qulu L, Daniels WMU, Russell V, Mabandla, MV. Searsia chirindensis reverses the potentiating effect of prenatal stress on the development of febrile seizures and decreased plasma interleukin-1β levels. Neurosci Res 2016;103:54-8.
  • 29. Watanabe H, Abe H, Takeuchi S, Tanaka R, Protective effect of microglial conditioning medium on neuronal damage induced by glutamate. Neurosci Lett 2000;289:53-6.
  • 30. Yavin E, Glozman S, Green P. Docosahexaenoic acid accumulation in the prenatal brain prooxidant and antioxidant features. J Mol Neurosci 2001;16:229-35.
  • 31. Lushchak VI, Bagnyukova TV. Hypoxia induces oxidative stress in tissues of a goby, the rotan Perccottus glenii. Comp Biochem Physiol B Biochem Mol Biol 2007;148:390-7.
  • 32. Oliveira CC, de Oliveira CV, de Grigoletto J, Ribeiro LR, Funck VR, Grauncke ACB. Et al. Anticonvulsant activity of β-caryophyllene against pentylenetetrazol-induced seizures. Epilepsy Behav 2016;56:26-31.
  • 33. Patel M. Mitochondrial dysfunction and oxidative stress: cause and consequence of epileptic seizures. Free Radic Biol Med 2004;37:1951-62.
  • 34. Abraham M, Biju CR, Babu G. Neuroprotective effect of lacosamide and pregabalin on pentylenetetrazole induced seizure models in rat. Br Biomed Bull 2014;2:1-5.
  • 35. Dhir A, Naidu PS, Kulkarni SK. Neuroprotective effect of nimesulide, a preferential COX-2 inhibitor, against pentylenetetrazol (PTZ)-induced chemical kindling and associated biochemical parameters in mice. Seizure 2007;16:691-7.
  • 36. Bernhardt LK, Madhyastha S, Bairy L, Kishore A. Status of the brain antioxidant system at different growing periods after prenatal stress and N-Acetyl cysteine administration. Folia Neuropathol 2017;55:38-48.
Primary Language en
Subjects Anatomy and Morphology, Physiology, Neurosciences, Psychiatry
Journal Section Original Articles
Authors

Orcid: 0000-0002-0161-6179
Author: Kübra ÇELİK (Primary Author)
Institution: Department of Neuroscience, Ege University Institute of Health Sciences, İzmir, Turkey
Country: Turkey


Orcid: 0000-0000-0000-0000
Author: Petek BİLİM
Institution: Department of Psychology, Toros University Faculty of Economics, Business Administration and Social Sciences, Mersin, Turkey
Country: Turkey


Orcid: 0000-0000-0000-0000
Author: Gurur GARİP
Institution: Department of Histology and Embryology, Ege University School of Medicine, İzmir, Turkey
Country: Turkey


Orcid: 0000-0000-0000-0000
Author: Burak DURMAZ
Institution: Department of Medical Biochemistry, Ege University School of Medicine, İzmir, Turkey
Country: Turkey


Orcid: 0000-0002-6383-6724
Author: Eser Y. SÖZMEN
Institution: Department of Medical Biochemistry, Ege University School of Medicine, İzmir, Turkey
Country: Turkey


Orcid: 0000-0000-0000-0000
Author: Meral BAKA
Institution: Department of Histology and Embryology, Ege University School of Medicine, İzmir, Turkey
Country: Turkey


Supporting Institution The Scientific Research Project Coordination of Ege University
Project Number 18-SBE-004/ 2018
Thanks We would like to thank Assoc. Prof. Dr. Timur Köse for his support on statistical analysis and The Department of Histology and Embryology staff for their assistance in the laboratory work.
Dates

Application Date : September 29, 2020
Acceptance Date : March 17, 2021
Publication Date : July 4, 2021

EndNote %0 The European Research Journal Prenatal stress impairs recognition memory and leads to neurodevelopmental deficits in hippocampus of adolescent rats with early acute pentylenetetrazole-kindling %A Kübra Çelik , Petek Bilim , Gurur Garip , Burak Durmaz , Eser Y. Sözmen , Meral Baka %T Prenatal stress impairs recognition memory and leads to neurodevelopmental deficits in hippocampus of adolescent rats with early acute pentylenetetrazole-kindling %D 2021 %J The European Research Journal %P -2149-3189 %V 7 %N 4 %R doi: 10.18621/eurj.801699 %U 10.18621/eurj.801699