The stability of the transcriptome during the estrous cycle in four regions of the mouse brain

Abstract

We analyzed the transcriptome of the C57BL/6J mouse hypothalamus, hippocampus, neocortex, and cerebellum to determine estrous cycle-specific changes in these four brain regions. We found almost 16,000 genes are present in one or more of the brain areas but only 210 genes, ∼1.3%, are significantly changed as a result of the estrous cycle. The hippocampus has the largest number of differentially expressed genes (DEGs) (82), followed by the neocortex (76), hypothalamus (63), and cerebellum (26). Most of these DEGs (186/210) are differentially expressed in only one of the four brain regions. A key finding is the unique expression pattern of growth hormone (Gh) and prolactin (Prl). Gh and Prl are the only DEGs to be expressed during only one stage of the estrous cycle (metestrus). To gain insight into the function of the DEGs, we examined gene ontology and phenotype enrichment and found significant enrichment for genes associated with myelination, hormone stimulus, and abnormal hormone levels. Additionally, 61 of the 210 DEGs are known to change in response to estrogen in the brain. 50 of the 210 genes differentially expressed as a result of the estrous cycle are related to myelin and oligodendrocytes and 12 of the 63 DEGs in the hypothalamus are oligodendrocyte- and myelin-specific genes. This transcriptomic analysis reveals that gene expression in the female mouse brain is remarkably stable during the estrous cycle and demonstrates that the genes that do fluctuate are functionally related.

A low-carbohydrate ketogenic diet promotes ganglioside synthesis via the transcriptional regulation of ganglioside metabolism-related genes

“…The analysis showed that changes in gene expression in the cerebral cortex mediated by the LCKD are relatively small when compared with those in the liver. Obvious changes (log 2 ratio < −4, P < 0.01) were observed only for the genes Prl and Gh (Table 2), which encode the pituitary hormones prolactin and growth hormone, respectively, and are known to be expressed in the cerebral cortex 34,35 . Several studies have reported a relationship between the expression of these genes and epilepsy 35,36 .…”

Sex‐biased hippocampal pathology in the 5XFAD mouse model of Alzheimer's disease: A multi‐omic analysis

“…During the estrous cycle expression of a small number of genes in the hippocampus of the female mouse changes significantly (DiCarlo, Vied, & Nowakowski, ; Spencer, Waters, Milner, & McEwen, ). To ensure that the estrous cycle did not confound comparisons of interest, the estrous stage was determined for sexually mature females (2 and 4 months of age) at the time of tissue collection.…”

Growth Hormone (GH) and Gonadotropin-Releasing Hormone (GnRH) in the Central Nervous System: A Potential Neurological Combinatory Therapy?

“…Similar to what happens in other brain areas, the hippocampus is a site of extrapituitary GH expression [ 120 , 121 ], which also leads to the notion that autocrine and/or paracrine regulatory mechanisms are involved in these actions. Interestingly, it was shown that GH expression in the amygdala, a functional related structure contiguous to the hippocampus, increased under chronic fear and during fear learning conditions [ 122 ].…”