The impact of early life stress and schizophrenia on motor and cognitive functioning: an experimental study.

Fredrick Otieno Oginga, Thabisile Mpofana
Author Information
  1. Fredrick Otieno Oginga: Department of Physiology, School of Laboratory Medicine and Medical Sciences, University of Kwa-Zulu Natal, Durban, South Africa.
  2. Thabisile Mpofana: Department of Physiology, School of Laboratory Medicine and Medical Sciences, University of Kwa-Zulu Natal, Durban, South Africa.

Abstract

Background: Early life stress (ELS) and parental psychopathology, such as schizophrenia (SZ), have been associated with altered neurobiological and behavioral outcomes later in life. Previous studies have investigated the effects of ELS and parental SZ on various aspects of behavior, however, we have studied the combined effects of these stressors and how they interact, as individuals in real-life situations may experience multiple stressors simultaneously.
Objective: The aim of this study was to investigate the impact of ELS and schizophrenia on locomotor activity, anxiety-like behavior, exploratory tendencies, and spatial memory in Sprague Dawley (SD) rats.
Methods: Male and female SD pups were randomly assigned to eight groups: control, ELS, schizophrenia, and ELS + schizophrenia. ELS was induced by prenatal stress (maternal stress) and maternal separation (MS) during the first 2 weeks of life, while SZ was induced by subcutaneous administration of ketamine. Behavioral tests included an open field test (OFT) for motor abilities and a Morris water maze (MWM) for cognitive abilities. ANOVA and Tukey tests were utilized to analyze the data.
Results: Our results show that ELS and parental psychopathology had enduring effects on SZ symptoms, particularly psychomotor retardation ( < 0.05). The OFT revealed increased anxiety-like behavior in the ELS group ( = 0.023) and the parental psychopathology group ( = 0.017) compared to controls. The combined ELS and parental psychopathology group exhibited the highest anxiety-like behavior ( = 0.006). The MWM analysis indicated impaired spatial memory in the ELS group ( = 0.012) and the combined ELS and parental psychopathology group ( = 0.003) compared to controls. Significantly, the exposure to ELS resulted in a decrease in the population of glial fibrillary acidic protein-positive (GFAP) astrocytes. However, this effect was reversed by positive parental mental health.
Conclusion: Our findings highlight the interactive effects of ELS and parental psychopathology on anxiety-like behavior and spatial memory in rats. ELS was linked to increased anxiety-like behavior, while SZ was associated with anhedonia-like behavior. Positive parenting augments neuroplasticity, synaptic function, and overall cognitive capacities.

Keywords

References

  1. J Clin Child Adolesc Psychol. 2014;43(5):777-90 [PMID: 24116918]
  2. Eur Child Adolesc Psychiatry. 2023 Sep;32(9):1691-1699 [PMID: 35416605]
  3. Neurochem Res. 2016 Apr;41(4):892-904 [PMID: 26577396]
  4. Neuron. 2018 Feb 7;97(3):670-683.e6 [PMID: 29397273]
  5. Behav Brain Res. 2017 Jan 15;317:16-26 [PMID: 27616342]
  6. Chronic Stress (Thousand Oaks). 2019 Jan-Dec;3: [PMID: 31608312]
  7. J Clin Psychiatry. 2019 Mar 19;80(4): [PMID: 30900848]
  8. Front Cell Dev Biol. 2021 May 25;9:665795 [PMID: 34113618]
  9. Methods Mol Biol. 2019;1916:99-103 [PMID: 30535687]
  10. Child Psychiatry Hum Dev. 2021 Jun;52(3):439-449 [PMID: 32712741]
  11. Dev Psychobiol. 2012 Sep;54(6):590-7 [PMID: 22714649]
  12. Front Cell Neurosci. 2017 Apr 19;11:87 [PMID: 28469557]
  13. Stress. 2014 Mar;17(2):157-68 [PMID: 24392966]
  14. Schizophr Bull. 2014 Jan;40(1):28-38 [PMID: 23960245]
  15. Mol Psychiatry. 2019 Jan;24(1):67-87 [PMID: 29679070]
  16. Antioxidants (Basel). 2019 May 05;8(5): [PMID: 31060341]
  17. Neuroimage Clin. 2023;37:103297 [PMID: 36563647]
  18. Scand J Psychol. 2021 Jun;62(3):374-385 [PMID: 33719054]
  19. J Child Fam Stud. 2016;25(11):3367-3380 [PMID: 27795659]
  20. J Neurotrauma. 2018 Jan 15;35(2):210-225 [PMID: 29017388]
  21. J Child Psychol Psychiatry. 2018 Apr;59(4):327-346 [PMID: 28714126]
  22. Pak J Pharm Sci. 2019 May;32(3):899-903 [PMID: 31278697]
  23. Front Physiol. 2021 Apr 15;12:659366 [PMID: 33935805]
  24. Nat Protoc. 2006;1(2):848-58 [PMID: 17406317]
  25. J Exp Neurosci. 2018 Jul 23;12:1179069518789149 [PMID: 30046253]
  26. Bipolar Disord. 2012 Sep;14(6):641-53 [PMID: 22938168]
  27. Genes (Basel). 2019 Jan 15;10(1): [PMID: 30650619]
  28. J Neurosci. 2020 Jan 2;40(1):12-21 [PMID: 31896560]
  29. Front Cell Neurosci. 2017 Jun 28;11:181 [PMID: 28701926]
  30. Psychopharmacology (Berl). 2011 Mar;214(1):55-70 [PMID: 20865251]
  31. APMIS. 1988 May;96(5):379-94 [PMID: 3288247]
  32. Behav Brain Res. 2013 Feb 1;238:279-88 [PMID: 23072929]
  33. Neurobiol Learn Mem. 2014 Oct;114:16-25 [PMID: 24727294]
  34. Behav Brain Res. 2009 Dec 7;204(2):396-409 [PMID: 19110006]
  35. Neuropsychopharmacology. 2017 Jan;42(1):99-114 [PMID: 27629365]
  36. Pharmacol Ther. 2010 Dec;128(3):419-32 [PMID: 20705091]
  37. PLoS One. 2015 Apr 17;10(4):e0124521 [PMID: 25886563]
  38. Dev Cogn Neurosci. 2016 Jun;19:233-47 [PMID: 27174149]
  39. BMC Psychiatry. 2004 Nov 26;4:40 [PMID: 15566566]
  40. J Child Fam Stud. 2018;27(6):1992-2003 [PMID: 29755251]
  41. PLoS One. 2011 Jan 27;6(1):e16514 [PMID: 21304584]
  42. Chronic Stress (Thousand Oaks). 2021 Dec 21;5:24705470211067181 [PMID: 34993376]
  43. PLoS One. 2014 Jan 21;9(1):e86283 [PMID: 24466003]
  44. Neuroscience. 2019 Jan 1;396:73-78 [PMID: 30458223]
  45. J Vis Exp. 2015 Feb 06;(96):e52434 [PMID: 25742564]
  46. Neurosci Biobehav Rev. 2018 Aug;91:138-152 [PMID: 27751733]
  47. Prog Neuropsychopharmacol Biol Psychiatry. 2016 Feb 4;65:68-77 [PMID: 26320029]
  48. Neuroscience. 2016 Mar 1;316:209-20 [PMID: 26742791]
  49. Front Behav Neurosci. 2023 Jan 11;16:1068271 [PMID: 36710953]
  50. Neurosci Lett. 2015 Jan 1;584:146-50 [PMID: 25451726]
  51. Schizophr Res. 2016 Mar;171(1-3):187-94 [PMID: 26811256]
  52. Transl Psychiatry. 2022 Nov 4;12(1):463 [PMID: 36333302]
  53. Brain Res. 2017 Jan 15;1655:270-276 [PMID: 26801829]
  54. Front Behav Neurosci. 2021 Nov 04;15:651263 [PMID: 34803620]
  55. Front Behav Neurosci. 2020 Nov 12;14:600766 [PMID: 33304248]
  56. Braz J Med Biol Res. 1999 Oct;32(10):1229-37 [PMID: 10510260]
  57. Psychiatr Genet. 2020 Feb;30(1):1-9 [PMID: 31764709]
  58. CNS Neurosci Ther. 2013 Jun;19(6):437-47 [PMID: 23611295]
  59. Transl Psychiatry. 2017 Apr 4;7(4):e1081 [PMID: 28375209]
  60. Psychopharmacology (Berl). 2008 May;198(1):141-8 [PMID: 18311557]
  61. Eur J Neurosci. 2006 Sep;24(5):1477-87 [PMID: 16965544]
  62. Nat Rev Endocrinol. 2009 Jul;5(7):374-81 [PMID: 19488073]
  63. JAMA. 1992 Mar 4;267(9):1244-52 [PMID: 1538563]
  64. Neurosci Bull. 2022 Aug;38(8):953-965 [PMID: 35349095]
  65. Singapore Med J. 2008 May;49(5):388-91 [PMID: 18465048]
  66. Stress. 2009 Nov;12(6):486-98 [PMID: 19206015]
  67. Mol Psychiatry. 2002;7(8):837-44 [PMID: 12232776]
  68. Histol Histopathol. 2002 Apr;17(2):639-48 [PMID: 11962763]
  69. Arch Gen Psychiatry. 1994 Mar;51(3):199-214 [PMID: 8122957]
  70. Pharmacol Rep. 2013;65(6):1451-61 [PMID: 24552992]
  71. Learn Mem. 2015 Aug 18;22(9):411-6 [PMID: 26286651]
  72. Int J Mol Sci. 2023 Feb 24;24(5): [PMID: 36901939]
  73. Lab Anim Res. 2015 Dec;31(4):166-73 [PMID: 26755919]
  74. Clin Child Fam Psychol Rev. 2022 Mar;25(1):222-247 [PMID: 35201543]
  75. J Abnorm Child Psychol. 2018 Jan;46(1):149-157 [PMID: 28215023]
  76. Neuron. 2013 Apr 10;78(1):81-93 [PMID: 23583108]
  77. Front Neuroanat. 2015 May 26;9:67 [PMID: 26074782]
  78. Brain Res Bull. 2001 Jul 15;55(5):585-95 [PMID: 11576755]
  79. Neuroscience. 2005;136(1):181-91 [PMID: 16182451]
  80. J Vis Exp. 2008 Sep 24;(19): [PMID: 19066539]

Word Cloud

Created with Highcharts 10.0.0ELSparentalpsychopathologybehaviorlifestressschizophreniaSZanxiety-likespatialgroup = 0effectsmemorycognitivecombinedassociatedstressorsstudyimpactSDratsinducedmaternaltestsOFTmotorabilitiesMWMincreasedcomparedcontrolsmentalearlyBackground:EarlyalteredneurobiologicalbehavioraloutcomeslaterPreviousstudiesinvestigatedvariousaspectshoweverstudiedinteractindividualsreal-lifesituationsmayexperiencemultiplesimultaneouslyObjective:aiminvestigatelocomotoractivityexploratorytendenciesSpragueDawleyMethods:Malefemalepupsrandomlyassignedeightgroups:controlELS + schizophreniaprenatalseparationMSfirst2 weekssubcutaneousadministrationketamineBehavioralincludedopenfieldtestMorriswatermazeANOVATukeyutilizedanalyzedataResults:resultsshowenduringsymptomsparticularlypsychomotorretardation< 005revealed023017exhibitedhighest006analysisindicatedimpaired012003Significantlyexposureresulteddecreasepopulationglialfibrillaryacidicprotein-positiveGFAPastrocytesHowevereffectreversedpositivehealthConclusion:findingshighlightinteractivelinkedanhedonia-likePositiveparentingaugmentsneuroplasticitysynapticfunctionoverallcapacitiesfunctioning:experimentalanxietytasklearning&navigationillness

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