Utilization of the allen gene expression atlas to gain further insight into glucocorticoid physiology in the adult mouse brain

Abstract

Glucocorticoid neurodynamics are the most crucial determinant of the hormonal effects in the mammalian brain, and depend on multiple parallel receptor and enzymatic systems, responsible for effectively binding with the hormone (and mediating its downstream molecular effects) and altering the local glucocorticoid content (by adding, removing or degrading glucocorticoids), respectively. In this study, we combined different computational tools to extract, process and visualize the gene expression data of 25 genes across 96 regions of the adult C57Bl/6J mouse brain, implicated in glucocorticoid neurodynamics. These data derive from the anatomic gene expression atlas of the adult mouse brain of the Allen Institute for Brain Science, captured via the in situ hybridization technique. A careful interrogation of the datasets referring to these 25 genes of interest, based on a targeted, prior knowledge-driven approach, revealed useful pieces of information on spatial differences in the glucocorticoidsensitive receptors, in the regional capacity for local glucocorticoid biosynthesis, excretion, conversion to other biologically active forms and degradation. These data support the importance of the corticolimbic system of the mammalian brain in mediating glucocorticoid effects, and particularly hippocampus, as well as the need for intensifying the research efforts on the hormonal role in sensory processing, executive control function, its interplay with brainderived neurotrophic factor and the molecular basis for the regional susceptibility of the brain to states of prolonged high hormonal levels. Future work could expand this methodology by exploiting Allen Institute's databases from other species, introducing complex tools of data analysis and combined analysis of different sources of biological datasets.

Recent advances in the crosstalk between the brain-derived neurotrophic factor and glucocorticoids

“…Given the role that GCs and BDNF seem to possess in stress, brain physiology and stress-related neuropsychiatric disease, and the close association between the expression of GR, BDNF and TrkB across brain regions (36), a reasonable question arises, whether the molecular biology of these two regulatory molecules interact, and if yes, at what level, under which conditions and impacting which cells/cellular networks/dynamics?…”

Role of testosterone: cortisol ratio in age- and sex-specific cortico-hippocampal development and cognitive performance

“…Many sexually dimorphic cortical and subcortical structures, such as the hippocampus, contain a high concentration of androgen and glucocorticoid receptors, at least in rodent models. 7,8 Human studies have also shown that age-and sex-specific levels of circulating androgens and glucocorticoids do influence morphometric properties of several cortical and hippocampal regions. [9][10][11][12][13] For instance, in postpubertal boys, lower testosterone levels were associated with greater cortical thickness in the left hemisphere, including the posterior cingulate gyrus, precuneus, and dorsolateral prefrontal cortex, and later the anterior cingulate gyrus.…”