Effect of high fat diet on maternal behavior, brain‐derived neurotrophic factor and neural stem cell proliferation in mice expressing human placental lactogen during pregnancy

Abstract

AbstractMaternal obesity is a serious health concern because it increases risks of neurological disorders, including anxiety and peripartum depression. In mice, a high fat diet (HFD) in pregnancy can negatively affect placental structure and function as well as maternal behavior reflected by impaired nest building and pup‐retrieval. In humans, maternal obesity in pregnancy is associated with reduced placental lactogen (PL) gene expression, which has been linked to a higher risk of depression. PL acting predominantly through the prolactin receptor maintains energy homeostasis and is a marker of placenta villous trophoblast differentiation during pregnancy. Impaired neurogenesis and low serum levels of brain‐derived neurotrophic factor (BDNF) have also been implicated in depression. Augmented neurogenesis in brain during pregnancy was reported in the subventricular zone (SVZ) of mice at gestation day 7 and linked to increased prolactin receptor signaling. Here, we used transgenic CD‐1 mice that express human (h) PL during pregnancy to investigate whether the negative effects of diet on maternal behavior are mitigated in these (CD‐1[hGH/PL]) mice. Specifically, we examined the effect of a HFD on nest building prepartum and pup retrieval postpartum, as well as on brain BDNF levels and neurogenesis. In contrast to wild‐type CD‐1[WT]mice, CD‐1[hGH/PL] mice displayed significantly less anxiety‐like behavior, and showed no impairment in prepartum nest building or postpartum pup‐retrieval when fed a HFD. Furthermore, the HFD decreased prepartum and increased postpartum BDNF levels in CD‐1[WT] but not CD‐1[hGH/PL] mice. Finally, neurogenesis in the SVZ as well as phosphorylated mitogen‐activated protein kinase, indicative of lactogenic signaling, appeared unaffected by pregnancy and diet at gestation day 7 in CD‐1[hGH/PL] mice. These observations indicate that CD‐1[hGH/PL] mice are resistant to the negative effects of HFD reported for CD‐1[WT] mice, including effects on maternal behaviors and BDNF levels, and potentially, neurogenesis. This difference probably reflects a direct or indirect effect of the products of the hGH/PL transgene.