Abstract
Glucocorticoids are produced by the adrenal cortex and regulate cell metabolism in a variety of organs. This occurs either directly, by acting on specific receptors in a variety of cells, or by stimulating catecholamine expression within neighbor cells of the adrenal medulla. In this way, the whole adrenal gland may support specific metabolic requirements to cope with stressful conditions from external environment or internal organs. In addition, glucocorticoid levels may increase significantly in the presence of inappropriate secretion from adrenal cortex or may be administered at high doses to treat inflammatory disorders. In these conditions, metabolic alterations and increased blood pressure may occur, although altered sleep-waking cycle, anxiety, and mood disorders are frequent. These latter symptoms remain unexplained at the molecular level, although they overlap remarkably with disorders affecting catecholamine nuclei of the brainstem reticular formation. In fact, the present study indicates that various doses of glucocorticoids alter the expression of genes and proteins, which are specific for reticular catecholamine neurons. In detail, corticosterone administration to organotypic mouse brainstem cultures significantly increases Tyrosine hydroxylase (TH) and Dopamine transporter (DAT), while Phenylethanolamine N-methyltransferase (PNMT) is not affected. On the other hand, Dopamine Beta-Hydroxylase (DBH) increases only after very high doses of corticosterone.
Highlights
Glucocorticoids are produced from the adrenal cortex and may be administered as a drug
enzyme-linked immunosorbent assay kit (ELISA) analysis showed that the medium culture contains a negligible quantity of corticosterone (0.0067 μM) compared to those selected for the study: 0.1, 0.5, 1, and 200 μM
In order to assess the effect of glucocorticoids on the brainstem, we exposed organotypic cultures following a subdivision of the brainstem in two blocks: the anterior part and the posterior part (Figure 1A–C)
Summary
Glucocorticoids are produced from the adrenal cortex and may be administered as a drug. Exogenous administration of glucocorticoids is a common way to treat a variety of disorders, including chronic inflammatory diseases In all these circumstances, glucocorticoids produce multiple effects, which may lead to Cushing syndrome [23]. All catecholamine nuclei are placed in a small region within the caudal part of the CNS known as the brainstem These nuclei are highly interconnected within the brainstem reticular formation, which contains noradrenaline (NA), dopamine (DA) and adrenaline (A) cell groups. Despite these nuclei being placed in a small brain area, their axons spread to the entire CNS. The lack of any influence in the present data of serum glucocorticoids was further demonstrated by administering the receptor antagonist, mifepristone, which did not vary the phenotype of controls, while it prevented the effects produced by exogenously administered glucocorticoids
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