Brainstem catecholaminergic neurons activated by hypoxemia express GR and are coordinately activated with fetal sheep hypothalamic paraventricular CRH neurons

Abstract

In late gestation, challenges to fetal homeostasis are accompanied by increases in adrenocorticotropin (ACTH) concentrations in fetal peripheral plasma and Fos ( c-fos protein) activation in corticotropin-releasing hormone (CRH) neurons of the fetal hypothalamic paraventricular nucleus (PVN). In adults, ventrolateral brainstem catecholaminergic (CA) neurons (A1/C1, A2/C2) project to the parvocellular neurons of the PVN, possess glucocorticoid receptors (GR) and are Fos activated in parallel with CRH neurons of the PVN during hypoxia. Such observations suggest a role for the aforementioned medullary neurons in the function of the hypothalamo–pituitary–adrenal axis. The present study utilized late gestation fetal sheep, stereotaxic methodology and retrograde axon tracing and immunocytochemical techniques to investigate the relationship between activation of fetal brainstem CA neurons and activation of fetal PVN CRH immunopositive neurons in response to hypoxemia. Results indicated that: (1) the largest brainstem CA projection to PVN CRH neurons is from A1/C1 neurons, (2) brainstem neurons exhibit GR immunostaining and (3) brainstem CA neurons show a strong correlation (A1/C1 — r 2=0.894, P<0.005; A2/C2 — r 2=0.848; P<0.002) of Fos activation with Fos activation in PVN CRH cells. We conclude that in late gestation the brainstem A1/C1 and A2/C2 areas are in position to influence the function of the hypothalamo–pituitary–adrenal axis during hypoxemic challenges to homeostasis in a fashion similar to that which has been demonstrated in the adult rat.