Maternal Interleukin-6 Hampers Hippocampal Neurogenesis in Adult Rat Offspring in a Sex-Dependent Manner

Abstract

Maternal immune activation (MIA) during pregnancy leads to long-lasting effects on brain development and function. Several lines of evidence suggest that the maternal inflammatory cytokine interleukin (IL)-6 plays a crucial role in the long-lasting effects of MIA on adult offspring. IL-6 is naturally produced during pregnancy in the absence of any underlying immune activation. The objective of this study was to assess whether this naturally occurring IL-6 has long-lasting effects on brain plasticity and function. Therefore, pregnant rats were given either an IL-6-neutralizing antibody (IL-6Ab) or vehicle during the third week of pregnancy. Newly born (doublecortin) and mature neurons (NeuN) were monitored in the hippocampus of adult male and female offspring. Prenatal IL-6Ab led to an enhanced number of newly born and mature neurons in the dentate gyrus of the hippocampus of male but not female adult offspring. This enhanced neurogenesis was associated with an increased propensity in memory acquisition in male offspring. Blunting the naturally occurring IL-6 during pregnancy did not have a significant long-lasting impact on astrocyte cell density (GFAP), or on anxiety-like behavior as assessed with elevated plus maze and open field tests. Taken together, these data suggest that maternal IL-6 contributes, at least in part, to the programming of the brain’s development in a sex-dependent manner.