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.

Abstract

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.

Genetic mechanisms of parenting

“…At the genetic level, early evidence suggests that expression of dopamine receptor genes D1 (DRD1) and D2 (DRD2) is upregulated during pregnancy in the rat (Mann, 2014). Furthermore, there is upregulated expression of dopamine receptor D4 (DRD4) and dopamine transporter DAT1 mRNA in the MPOA following pup exposure, regardless of maternal parity (Akbari et al, 2013). Taken together, this evidence suggests a strong role of dopamine in rat maternal regulation.…”

Neuroendocrine regulation of maternal behavior

“…A broader genetic approach to elucidate the neurobiological bases of motherhood involves asking what genes ae up or down regulated as a function of parturition and lactation (Akbari et al, 2013). Microarray analyses of brain regions found significant effects of pup exposure and parity on the expression of dopamine and glucocorticoid-related genes, the mu-1 opiate receptor, and the GABA and serotonin receptor genes in the MPOA.…”

Genetic and neuroendocrine regulation of the postpartum brain

“…As indicated in Fig. 1, a subset of genes (~50) have been well-studied (including via pharmacological manipulations) in the context of the postpartum brain or maternal phenotype and most of these are related to known modulators of maternal behavior and physiology, including estradiol, oxytocin, vasopressin, prolactin, progesterone, dopamine, and GABA (Francis et al, 2002; Salzberg et al, 2002; Numan and Insel, 2003; Zhao et al, 2012a; Akbari et al, 2013; Bridges, 2015; de Moura et al, 2015; Keebaugh et al, 2015; Mileva-Seitz et al, 2015). Further, the Jackson Laboratory maintains a database of modifications of genes that lead to overt maternal behavioral or physiological disruptions in mice and currently about 150 genes have been identified (www.jax.org) (Grubb et al, 2014).…”

“…Penk was also found to be differentially expressed in a study on rat hippocampus (Kinsley et al, 2008). In a relatively recent maternal rat study on MPOA and amygdala (Akbari et al, 2013), two of the genes were also in the top 700 maternal genes, namely Drd1a and Oprm1 .…”