Previous research has led to the idea that derived traits can arise through the evolution of novel roles for conserved genes. We explored whether Neuropeptide Y-like signaling, a conserved pathway that regulates food-related behavior, is involved in a derived, nutritionally-related trait, division of labor in worker honey bees. Transcripts encoding two NPY-like peptides were expressed in separate populations of brain neurosecretory cells, consistent with endocrine functions. NPY-related genes were upregulated in the brains of older foragers compared to younger bees performing brood care ("nurses"). A subset of these changes can be attributed to nutrition, but NPF peptide treatments did not influence sugar intake. These results contrast with recent reports of more robust associations between division of labor and the related insulinsignaling pathway and suggest that some elements of molecular pathways associated with feeding behavior may be more evolutionarily labile than others.
Sexual differentiation of the neonatal rat brain is regulated by dynamic processes occurring at the level of DNA, resulting in sexually dimorphic gene expression. Steroid hormone receptors act partly in the developing brain by recruiting co-activators, thereby increasing acetylation of histones and gene expression. Recent data indicate that sexual differentiation of the brain may also result, in part, from differences in promoter methylation patterns of some steroid responsive genes. Methylation of DNA is an epigenetic process that can decrease gene expression without altering the original DNA sequence. DNA cytosine-5-methyltransferases (DNMTs) 1 and 3a are two factors that induce methylation. We investigated whether sex differences in the expression of DNMT1 and DNMT3a were apparent in the amygdala, preoptic area, and medial basal hypothalamus at different time points during development. We found that females express significantly more DNMT3a mRNA and protein in the amygdala, but not within the preoptic area or the medial basal hypothalamus at postnatal day 1. There are no sex differences in DNMT3a mRNA or protein at postnatal day 10. Furthermore, no sex differences were observed in the expression of DNMT1 at either time point. As most sex differences in the brain are a result of a higher level of gonadal steroid hormone exposure in males at birth, we examined whether dihydrotestosterone or estradiol exposure would reduce DNMT3a expression in neonatal female rats. We found that both estradiol and dihydrotestosterone treatment significantly reduced DNMT3a, but not DNMT1, mRNA expression within the developing amygdala. Our results indicate that sex differences in DNMT3a within the developing amygdala are partly due to steroid exposure. This suggests that steroid hormone exposures may program lasting differences in amygdala function by altering the expression of the epigenetic factor, DNMT3a.
Nuclear receptor function on DNA is regulated by the balanced recruitment of coregulatory complexes. Recruited proteins that increase gene expression are called coactivators, and those that decrease gene expression are called corepressors. Little is known about the role of corepressors, such as nuclear receptor corepressor (NCoR), on the organization of behavior. We used real-time PCR to show that NCoR mRNA levels are sexually dimorphic, that females express higher levels of NCoR mRNA within the developing amygdala and hypothalamus, and that NCoR mRNA levels are reduced by estradiol treatment. To investigate the functional role of NCoR on juvenile social behavior, we infused small interfering RNA targeted against NCoR within the developing rat amygdala and assessed the enduring impact on juvenile social play behavior, sociability, and anxiety-like behavior. As expected, control males exhibited higher levels of juvenile social play than control females. Reducing NCoR expression during development further increased juvenile play in males only. Interestingly, decreased NCoR expression within the developing amygdala had lasting effects on increasing juvenile anxiety-like behavior in males and females. These data suggest that the corepressor NCoR functions to blunt sex differences in juvenile play behavior, a sexually dimorphic and hormone-dependent behavior, and appears critical for appropriate anxiety-like behavior in juvenile males and females.
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