Prenatal Paroxetine Exposure Alters Oxidative, Inflammatory, Neurobehavioural, and Cholinergic Markers in the Hippocampus of Male and Female Mice Offspring in a Depression Model

Abstract

Background: Depression is a debilitating mental disorder that is impairs behavioural abilities due to its symptomatic expression but much more severe in gestational period due to its impact on maternal and child’s health. The study focused on the impacts of paroxetine and stress on offspring health exploring its neurobehavioural across age trajectories of infancy, adolescent and adulthood while various oxidative, inflammatory and neurochemical enzymes biomarkers were assayed for in the brain hippocampal region. Materials and Methods: Eighty 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 (2.5mg/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. Results: Key findings showed that paroxetine causes reduced brain weight especially in female than male with an increase correct alternation activities in infancy and adulthood than in adolescent. It also reduces oxidative activities when compared to control but only have little effect in balancing oxidant in severe reversal conditions, while also potentiating neurochemical enzyme activity in female than in male. Paroxetine showed a marked reduction of pro-inflammatory cytokines activities in male and female mice offspring. Conclusion: Paroxetine shows clinical importance in the management of gestational depression but shows altering effects in neuronal weight and enzymes, oxidation and concentration in release of cytokines in the hippocampal brain region.