An examination of changes in maternal neuroimmune function during pregnancy and the postpartum period

Abstract

There is strong evidence that the immune system changes dramatically during pregnancy in order to prevent the developing fetus from being "attacked" by the maternal immune system. Due to these alterations in peripheral immune function, many women that suffer from autoimmune disorders actually find significant relief from their symptoms throughout pregnancy; however, these changes can also leave the mother more susceptible to infections that would otherwise be mitigated by the inflammatory response (Robinson and Klein, 2012). Only one other study has looked at changes in microglial number and morphology during pregnancy and the postpartum period (Haim et al., 2016), but no one has yet examined the neuroimmune response following an immune challenge during this time. Therefore, in this study, we investigated the impact of an immune challenge during various time-points throughout pregnancy and the postpartum period on the expression of immune molecules in the brain of the mother and fetus. Our results indicate that similar to the peripheral immune suppression measured during pregnancy, we also see significant suppression of the immune response in the maternal brain, particularly during late gestation. In contrast to the peripheral immune system, immune modulation in the maternal brain extends moderately into the postpartum period. Additionally, we found that the fetal immune response in the brain and placenta is also suppressed just before parturition, suggesting that cytokine production in the fetus and placenta are mirroring the peripheral cytokine response of the mother.

Neuroimmunology of the female brain across the lifespan: Plasticity to psychopathology

“…In late pregnancy, there is a reduction in the number of microglia in the brain, specifically in the medial prefrontal cortex, nucleus accumbens, basolateral amygdala and dorsal hippocampus, which seems to be a result of reduced proliferation, rather than increased apoptosis (Haim et al, 2017). In accordance, neuroimmune responses of the maternal brain to immune/inflammatory challenge are suppressed, especially in late pregnancy (Sherer et al, 2017). For example, up-regulation in gene expression for the cytokines, IL-1β and IL-6 in response to bacterial endotoxin LPS administration is markedly attenuated in the prefrontal cortex, preoptic area, hypothalamus and hippocampus of late pregnant rats, compared with non-pregnant females (Sherer et al, 2017).…”

Towards an understanding of women's brain aging: the immunology of pregnancy and menopause

“…Alternations in microglia, the brain's innate immune cells, have been detected in female rats, with a significant reduction in microglial density and count during late pregnancy and early postpartum in the amygdala, medial prefrontal cortex, nucleus accumbens, and hippocampus [50], indicating a central role of neuroimmune mechanisms in maternal brain plasticity. Hippocampal concentrations of the cytokines interleukin (IL)-6 and IL-10 have been shown to increase in rats after parturition [50], and distinct changes in IL-6 and IL-1β expression have been observed in the hippocampus and medial prefrontal cortex during pregnancy and postpartum [51].…”

Inflammatory markers in women with postpartum depressive symptoms

“…Further, the postpartum period has been characterized by elevated cytokine levels and high infiltration of immune cells (Shynlova, Nedd‐Roderique, Li, Dorogin, & Lye, ; Yoshii, Kitahara, Ueta, Matsuno, & Ezaki, ). Contradictory to the increased peripheral activity reported in the postpartum period, studies in rodents have indicated a decreased number of microglial cells in the brain and a suppression of the cytokine response in the maternal brain during late pregnancy and early postpartum (Haim et al, ; Posillico & Schwarz, ; Sherer, Posillico, & Schwarz, ).…”