Immunohistochemistry and Histology Evaluation of Neurodevelopmental and Neurocognitive Changes in the Offspring of Depressed Mice Administered Paroxetine Prenatally
Israel O. Efejene
DELSU Joint Canada-Israel Neuroscience and Biopsychiatry Laboratory, Department of Pharmacology, Faculty of Allied Health Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria and Department of Pharmacology, Faculty of Basic Medical Sciences, Southern Delta University, Ozoro, Delta State, Nigeria.
Benneth Ben-Azu
DELSU Joint Canada-Israel Neuroscience and Biopsychiatry Laboratory, Department of Pharmacology, Faculty of Allied Health Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria.
Anthony T. Eduviere
DELSU Joint Canada-Israel Neuroscience and Biopsychiatry Laboratory, Department of Pharmacology, Faculty of Allied Health Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria.
Osuvwe C. Orororo *
Department of Medical Biochemistry, Faculty of Basic Medical Sciences, College of Health Sciences, Delta State University, Abraka, Delta State, Nigeria.
Meashack O. Ijomone
Department of Anatomy, Faculty of Basic Medical Sciences University of Medical Sciences, Ondo State, Nigeria.
Mega O. Oyovwi
Department of Human Physiology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Delta State, Nigeria.
Michael E. Aisuodionoe
Department of Human Physiology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Delta State, Nigeria.
Abdulwasiu A. Busari
Department of Pharmacology, Therapeutics and Toxicology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Lagos, Lagos State, Nigeria.
*Author to whom correspondence should be addressed.
Abstract
Depression, a prevalent biopsychiatry disability leading to dysfunction behavioural abilities due to its symptomatic expression, is much more severe in gestational period affected both maternal and child’s health. Paroxetine, a selective serotonin reuptake inhibitors (SSRI) is used in the treatment of chronic and severe depression, but its impact on foetus via utero exposure has not been fully established. Thus, this study assessed the neurodevelopmental and neurocognitive changes in the offspring of depressed mice administered paroxetine prenatally. The effects on miroglia, neuromodulatory, neuroinhibitory, apoptotic and neuronal architectural mapping at adulthood biomarkers were assayed for in the selected brain hippocampal region of cornu ammonis and dendate gyrus. Seventy female Swiss mice (25-30g) were induced with prenatal depression using chronic unpredictable mild stress (CUMS) in pregnant Swiss dams at gestation days (GD) 13 to 19. Group 1 which served as control, consisted offspring of non-CUMS-treated dams, and received saline (2 mL/kg, p.o). Groups 2 and 3 include offspring of non-CUMS-treated dams and received paroxetine (2.5 mg/kg and 5mg/kg, p.o) from GDs 13-19. Group 4 consist of offspring of CUMS-exposed dams and served as CUMS control. Groups 5 and 6 consist of offspring of CUMS-exposed dams, treated with paroxetine (2.5 and 5 mg/kg, p.o) from GD 13-19. Offspring (pups: males and females) were weaned at postnatal day (PND) 21-22 and randomly assigned into 6 groups (n =10) above. Paroxetine potentiated IBA-1 across hippocampal regions except paroxetine reversal intervention in cornu ammonis 1 (CA1) and dendate gyrus (DG) of male and that of the female CA3 and DG. Paroxetine also potentiated BDNF across the brain region except in the reversal effect of CA1 region in female mice when compared to CUMS. In addition, paroxetine increased PARV across hippocampal region except CUMS and paroxetine groups when compared to control in male. Paroxetine advanced BCL-2 and reduced BAX across hippocampal regions in both sexes while paroxetine potentiated normal neuronal cells, and CUMS showed the expression of pyknotic cells. These implychanges in microglia function and paroxetine displayed improved hippocampal neuronal life, neuroinhibitory and neurogenesis with a normal neuronal architectural circuitry except in stressed mice in CA1, CA3 and DG.
Keywords: Immunohistochemistry, neurodevelopmental, neurocognitive changes, depression