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

Maternal 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.