Project description:Hormonal fluctuations throughout the ovarian cycle contribute to femalesâ?? higher vulnerability to anxiety disorders when compared to males. Notably, such sex differences are controlled by regulation of genes in the medial prefrontal cortex (mPFC) including the transcription factor early growth response 1 (Egr1) in rats, which highlights a control of anxiety-like behaviors by sexually-biased gene expression. We therefore undertook a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult mPFC transcriptome and report that proestrus and diestrus females (with high and low ovarian hormones levels, respectively) exhibited a partly-opposed sexually-biased transcriptome. Surprisingly, the extent of regulations within females vastly exceeded sex differences, and support a multi-level reorganization of synaptic function across the estrous cycle. Furthermore, genome-wide analysis of Egr1 binding highlighted its role in controlling the synapse-related genes varying within females, and the sex- and estrous cycle-dependent transcriptomic reorganization in the rat mPFC. Early growth response 1 (Egr1) binding profiling in the adult rat medial prefrontal cortex of males, proestrus females, and diestrus females. A total of 9 animals were used, corresponding to 3 Males, 2 proestrus females, and 4 diestrus females.
Project description:Hormonal fluctuations throughout the ovarian cycle contribute to females’ higher vulnerability to anxiety disorders when compared to males. Notably, such sex differences are controlled by regulation of genes in the medial prefrontal cortex (mPFC) including the transcription factor early growth response 1 (Egr1) in rats, which highlights a control of anxiety-like behaviors by sexually-biased gene expression. We therefore undertook a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult mPFC transcriptome and report that proestrus and diestrus females (with high and low ovarian hormones levels, respectively) exhibited a partly-opposed sexually-biased transcriptome. Surprisingly, the extent of regulations within females vastly exceeded sex differences, and support a multi-level reorganization of synaptic function across the estrous cycle. Furthermore, genome-wide analysis of Egr1 binding highlighted its role in controlling the synapse-related genes varying within females, and the sex- and estrous cycle-dependent transcriptomic reorganization in the rat mPFC.
Project description:Hormonal fluctuations throughout the ovarian cycle contribute to females’ higher vulnerability to anxiety disorders when compared to males. Notably, such sex differences are controlled by regulation of genes in the medial prefrontal cortex (mPFC) including the transcription factor early growth response 1 (Egr1) in rats, which highlights a control of anxiety-like behaviors by sexually-biased gene expression. We therefore undertook a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult mPFC transcriptome and report that proestrus and diestrus females (with high and low ovarian hormones levels, respectively) exhibited a partly-opposed sexually-biased transcriptome. Surprisingly, the extent of regulations within females vastly exceeded sex differences, and support a multi-level reorganization of synaptic function across the estrous cycle. Furthermore, genome-wide analysis of Egr1 binding highlighted its role in controlling the synapse-related genes varying within females, and the sex- and estrous cycle-dependent transcriptomic reorganization in the rat mPFC.
Project description:Hormonal fluctuations throughout the ovarian cycle contribute to femalesâ higher vulnerability to anxiety disorders when compared to males. Notably, such sex differences are controlled by regulation of genes in the medial prefrontal cortex (mPFC) including the transcription factor early growth response 1 (Egr1) in rats, which highlights a control of anxiety-like behaviors by sexually-biased gene expression. We therefore undertook a large-scale characterization of sex differences and their interaction with the estrous cycle in the adult mPFC transcriptome and report that proestrus and diestrus females (with high and low ovarian hormones levels, respectively) exhibited a partly-opposed sexually-biased transcriptome. Surprisingly, the extent of regulations within females vastly exceeded sex differences, and support a multi-level reorganization of synaptic function across the estrous cycle. Furthermore, genome-wide analysis of Egr1 binding highlighted its role in controlling the synapse-related genes varying within females, and the sex- and estrous cycle-dependent transcriptomic reorganization in the rat mPFC. mRNA profiling of 2-3 month-old males and females Sprague-Dawley rats in either Proestrus or Diestrus. A total of 11 samples were analyzed, corresponding to 4 males, 3 proestrus females, and 4 diestrus females.
Project description:To unravel the gene expression changes during postnatal prefrontal cortex development, RNA-seq was performed in the rat medial prefrontal cortex at five time points from early life to adulthood (postnatal day 8, 14, 21, 35 and 70) and differential expression of protein-coding genes, lincRNAs and alternative exons was analyzed. A switch from neuronal network development to maintenance during postnatal rat prefrontal cortex development was shown.
Project description:Animal models provide opportunity to study neurobiological aspects of human alcoholism. Changes in gene expression have been implicated in mediating brain function, including reward system and addiction. The current study aimed to identify novel genes that may underlie ethanol preference. Microarray analysis comparing gene expression in nucleus accumbens (NAc), hippocampus (HP) and prefrontal medial cortex (mPFC) was performed in two rat strains selected for extreme levels of ethanol preference - Warsaw High Preferring (WHP) and Warsaw Low Preferring (WLP). The identified candidate genes may underlie differential ethanol preference in rat model of alcoholism. This is analysis of 18 RNA samples, including 9 technical replicates. Two strains of rats selected for extreme levels of ethanol preference (low preferring WLP and high preferring WHP) were compared. Three brain areas (nucleus accumbens, prefrontal medial cortex and hippocampus) were studied. For each brain area, 6 RNA samples (including 3 technical replicates) were analyzed. Each RNA sample consist of of equal amounts of total RNA from 3 male rats. Comparisons: Nucleus accumbens of WHP vs. Nucleus accumbens of WLP; Prefrontal medial cortex of WHP vs. Prefrontal medial cortex of WLP; Hippocampus of WHP vs. Hippocampus of WLP. 3 biological replicates in each comparison.
Project description:The hippocampus is a critical brain region for coordinating learning, memory, and behavior. In adult females, the estrus cycle alters these functions through the activity of steroids hormones, with well-characterized effects on cellular physiology and behavior. However,the molecular genetic basis of these outcomes has not been systematically explored. In order to better understand the role of sex and the estrous cycle in the hippocampus, we profiled the transcriptome of hippocampi from female mice in each stage of the estrus cycle, along with those of males. We identify only subtle sex differences in gene expression between the sexes on average, yet comparing males to individual estrous stages reveals ~100 genes deviating from male expression patterns at one point in their cyclic fluctuations across estrous cycle. These estrus-responsive genes are especially enriched in oligodendrocytes and glycinergic neurons, and are potentially regulated downstream of estrogen receptor repressed pathways. To further understand our previous observations of female- and estrous-specific behavioral outcomes in knockout of Cnih3, we performed the same profiling in the knockout strain. Surprisingly, Cnih3 knockouts showed far broader transcriptomic differences between estrous cycle stages and males, despite very subtle within-group-across-genotype expression changes. We show that Cnih3 knockout drives expression changes in opposing directions between males and all points of the estrous cycle, extensively accentuating the magnitude of sex-differential hippocampal gene expression compared to wild-types. We thus provide a novel resource characterizing estrous-specific gene expression patterns in the adult hippocampus, which can provide insights into mechanisms of sex differential neuropsychiatric functions and dysfunctions, and identify a role for Cnih3 in buffering the female brain against the transcriptional effects of estrous.