The effects of parity and maternal behavior on gene expression in the medial preoptic area and the medial amygdala in postpartum and virgin female rats: A microarray study.

To determine the pattern of gene expression in brains associated with mothering during the postpartum period, in the present study we assessed gene expression through microarrays in four groups of female rats: two groups of new mothers that were experiencing the hormonal and neurochemical changes associated with pregnancy and parturition, and two groups of virgin females that were not. Within each of these parity groups we assessed one group of animals that was exposed to and responded to pups and engaged in maternal behavior, and one group left without any exposure to pups and therefore had no maternal experience. We explored the pattern of expression of genes related to the hormones, neurotransmitters, and modulatory neuropeptides associated with maternal behavior within the medial preoptic area (MPOA) and the medial amygdala (MeA) in the rat. Within the MPOA there were significant main effects of pup exposure for the dopamine-related genes (DRD4 and dopamine transporter, DAT), the glucocorticoid-related gene (CYPX1B1a), the opioid receptor µ-1 gene (OPRM1) and the gamma-aminobutyric acid (GABA) receptor gene (GABAbRid). OPRM1 and the serotonin-related gene that regulates biosynthesis of serotonin (5HTR2A) showed a main effect of parity. For both sets of analyses, higher gene expression was associated with pup exposure and parity. Genes expressed in the MeA tended to reside in the glucocorticoid family. The microarrays were able to identify, on a transcriptional level, a list of candidate genes involved in maternal behavior and the factors that surround it.

Menin links the stress response to genome stability in Drosophila melanogaster.

BACKGROUND: The multiple endocrine neoplasia type I gene functions as a tumor suppressor gene in humans and mouse models. In Drosophila melanogaster, mutants of the menin gene (Mnn1) are hypersensitive to mutagens or gamma irradiation and have profound defects in the response to several stresses including heat shock, hypoxia, hyperosmolarity and oxidative stress. However, it is not known if the function of menin in the stress response contributes to genome stability. The objective of this study was to examine the role of menin in the control of the stress response and genome stability. METHODOLOGY/PRINCIPAL FINDINGS: Using a test of loss-of-heterozygosity, we show that Drosophila strains lacking a functional Mnn1 gene or expressing a Mnn1 dsRNA display increased genome instability in response to non-lethal heat shock or hypoxia treatments. This is also true for strains lacking all Hsp70 genes, implying that a precise control of the stress response is required for genome stability. While menin is required for Hsp70 expression, the results of epistatic studies indicate that the increase in genome instability observed in Mnn1 lack-of-function mutants cannot be accounted for by mis-expression of Hsp70. Therefore, menin may promote genome stability by controlling the expression of other stress-responsive genes. In agreement with this notion, gene profiling reveals that Mnn1 is required for sustained expression of all heat shock protein genes but is dispensable for early induction of the heat shock response. CONCLUSIONS/SIGNIFICANCE: Mutants of the Mnn1 gene are hypersensitive to several stresses and display increased genome instability when subjected to conditions, such as heat shock, generally regarded as non-genotoxic. In this report, we describe a role for menin as a global regulator of heat shock gene expression and critical factor in the maintenance of genome integrity. Therefore, menin links the stress response to the control of genome stability in Drosophila melanogaster.