Pregnancy-associated oxidative stress and inflammation are not associated with impaired maternal neuronal activity or memory function

Abstract

Pregnancy is associated with neural and behavioral plasticity, systemic inflammation, and oxidative stress. Yet, the impact of systemic inflammation and oxidative stress on maternal neural and behavioral plasticity during pregnancy are unclear. We hypothesized that the maternal hippocampal CA1, a brain region associated with cognition, would be protected from pregnancy-associated systemic elevations in inflammation and oxidative stress, mediating stable peripartum cognitive performance. Cognitive performance was tested using novel object recognition (recollective memory), Morris water maze (spatial memory), and open field (anxiety-like) behavior tasks in female Sprague-Dawley rats of varying reproductive states [non-pregnant (nulliparous), pregnant (near term), and two months post-pregnancy (primiparous); n = 7-8/group]. Plasma and CA1 proinflammatory cytokines were measured using a MILLIPLEX(R) magnetic bead assay. Plasma oxidative stress was measured via advanced oxidation protein products (AOPP) assay. CA1 markers of oxidative stress, neuronal activity, and apoptosis were quantified via western blotting. Our results demonstrate CA1 oxidative stress-associated markers were elevated in pregnant compared to nulliparous rats (p [≤] 0.017) but were equivalent levels in pregnant and primiparous rats. In contrast, reproductive state did not impact CA1 inflammatory cytokines, neuronal activity, or apoptosis. Likewise, there was no effect of reproductive state on recollective or spatial memory. Even so, spatial learning was impaired (p [≤] 0.007) while anxiety-like behavior (p [≤] 0.034) was reduced in primiparous rats. Overall, our data suggest maternal hippocampal CA1 is protected from systemic inflammation but vulnerable to peripartum oxidative stress. Thus, peripartum oxidative stress elevations, such as in pregnancy complications, may contribute to peripartum neural and behavioral plasticity.