Sex differences in epigenetic mechanisms may underlie risk and resilience for mental health disorders.

Alterations in the epigenetic programming of sex differences in the brain may underlie sexually dimorphic neurodevelopmental disorders. Sex differences have been found in DNA methyltransferases 3a, DNA methylation patterns, MeCP2, and nuclear corepressor within the developing brain. Natural variations in these epigenetic mechanisms have profound consequences on gene expression and brain function.

Epigenetic organization of brain sex differences and juvenile social play behavior.

The study of epigenetic mechanisms is important for elucidating how gene-by-environment interactions can have lasting outcomes on brain function and behavior. In general, studies of epigenetic processes mainly focus on the methylation status of DNA. While methylation of DNA alone can interfere with gene transcription, it is the binding of methyl-CpG binding proteins to methylated DNA, and subsequent recruitment of nuclear corepressors and histone deacetylases, that results in more efficient gene repression.

The nuclear receptor corepressor has organizational effects within the developing amygdala on juvenile social play and anxiety-like behavior.

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.

Corepressors, nuclear receptors, and epigenetic factors on DNA: a tail of repression.

The differential exposure to circulating steroid hormones during brain development can have lasting consequences on brain function and behavior; therefore, the tight control of steroid hormone action within the developing brain is necessary for the expression of appropriate sex-typical behavior patterns later in life. The restricted control of steroid hormone action at the level of the DNA can be accomplished through the recruitment of coregulatory complexes. Nuclear receptor action can either be enhanced by the recruitment of coactivator complexes or suppressed by the formation of corepressor complexes.

Postmenopausal increase in KiSS-1, GPR54, and luteinizing hormone releasing hormone (LHRH-1) mRNA in the basal hypothalamus of female rhesus monkeys.

The G-protein coupled receptor, GPR54, and its ligand, kisspeptin-54 (a KiSS-1 derived peptide) have been reported to be important players in control of LHRH-1 release. However, the role of the GPR54 signaling in primate reproductive senescence is still unclear. In the present study we investigated whether KiSS-1, GPR54, and LHRH-1 mRNA in the brain change after menopause in female rhesus monkeys using quantitative real-time PCR.

Indicators of developmental deviance in individuals at risk for schizophrenia.

Schizophrenia is generally conceptualized as a neurodevelopmental disorder. In order to examine psychometrically-identified individuals at risk for schizophrenia in terms of indicators of developmental deviance, we examined digit ratios, nailfold plexus visibility, and dermatoglyphic features in young adults with elevated scores on the Social Anhedonia Scale. These individuals were compared to an age-matched control group.

Microarray profiling of gene expression patterns in adult male rat brain following acute progesterone treatment.

Progesterone can influence various behaviors in adult male rats, however, little is known about which particular genes are regulated by progesterone in the male rat brain. Using focused microarray technology, we where able to define a subset of genes that are responsive to progesterone. Nylon membrane-based cDNA microarrays were used to profile gene expression patterns in the preoptic area/mediobasal hypothalamus (POA/MBH) of male rat brain 7 h following a single injection of progesterone.

Gene array profiling of large hypothalamic CNS regions in lactating and randomly cycling virgin mice.

A dramatic example of neuronal and physiological plasticity in adult mammals occurs during the transition from a non-maternal to a maternal, lactating state. In this study, we compared gene expression within a large continuous region of the CNS involved in maternal behaviors (hypothalamus, preoptic regions, and nucleus accumbens) between lactating (L) (postpartum Day 7) and randomly cycling virgin (V) outbred mice. Using high-density oligonucleotide arrays representing 11,904 genes, two statistical algorithms were used to identify significant differences in gene expression: robust multiarray (P < 0.

Dopaminergic activation of estrogen receptors in neonatal brain alters progestin receptor expression and juvenile social play behavior.

Steroid receptor activation in developing brain influences a variety of cellular processes that endure into adulthood, altering both behavior and physiology. We report that estrogen receptors can be activated in a ligand-independent manner within developing brain by membrane dopamine receptors. Neonatal treatment with either estradiol or a dopamine D1 receptor agonist can increase the expression of an estrogen receptor-regulated gene (i.