Influences of the prenatal environment on the development of the hypothalamus were indicated in studies investigating the effects of prenatal high fat diet exposure. Perinatal high fat diet

exposure was shown to alter the development of hypothalamic leptin and insulin signaling (reviewed in (Coupe and Bouret, 2013)). Our studies showed that adult offspring of PNS rats had decrease expression of neuropeptide-Y and agouti-related peptide, and increased expression of proopiomelanocortin in the arcuate nucleus of the hypothalamus, but these increases correlated with the increased adiposity and leptin in these animals, making it hard to distinguish cause and consequence (Boersma et al., CT99021 mouse 2014a). Neuronal development of the hypothalamus takes place primarily during the early postnatal period (Coupe and Bouret, 2013), therefore direct effects of PNS on the development of this brain area click here is unllikely. In studies investigating the effects of prenatal diet, it has been shown that leptin levels and signaling were altered in offspring from high fat diet fed dams ( Sun et al., 2012). During development leptin acts as a trophic factor, which in turn may alter neuronal development (reviewed in ( Sun et al., 2012 and Bouret, 2009)). Whether PNS also alters the development of the leptin signaling pathways remains to be determined. While circulating leptin levels were not different

between control and PNS offspring ( Tamashiro et al., 2009) in this study, other hormones related to energy homeostasis, such as insulin, ghrelin and amylin have critical roles during development and may have been altered by PNS and have had significant influences on brain maturation. Metalloexopeptidase Future studies into neuronal development of feeding related brain areas are needed to investigate this. PNS may alter development of brain areas involved in emotion and reward through alterations in expression of trophic factors such as brain derived neurotropic factor (BDNF or Bdnf). PNS

was shown to decrease expression of Bdnf in hippocampus ( Neeley et al., 2011) and amygdala ( Boersma et al., 2014b). With its important role in neuronal development, a decrease in Bdnf may have consequences for the development of a wide variety of neuronal pathways (reviewed in ( Park and Poo, 2013)) and thereby it may affect the phenotype of the PNS offspring. Neeley and colleagues showed that the effects of PNS on Bdnf expression in the hippocampus are strain dependent. They showed that baseline Bdnf expression was increased in PNS offspring of the Sprague Dawley and Lewis rat strains, but that PNS did not affect baseline Bdnf expression in the Fischer 344 strain ( Neeley et al., 2011). As mentioned previously, the Lewis and Fischer strains were differentially affected by PNS: PNS Lewis rats showed alterations in depression-like behaviors, whereas the Fischer 344 strain seems relatively unaffected by PNS ( Stohr et al., 1998).