Psychological and Brain Sciences Brown Bag Seminar: Joel Geerling, Neurology

Wednesday, September 26, 2018 - 11:30am
Seashore Hall

Aldosterone-Sensitive Brainstem Neurons and Sodium Appetite

Joel Geerling, M.D., Ph.D., Assistant Professor, Department of Neurology, University of Iowa

Abstract: Aldosterone, a steroid hormone, is produced in the adrenal cortex during states of body sodium deficiency, low blood volume, or excess potassium. Aldosterone causes renal and other excretory epithelia to retain sodium and eliminate potassium from the body. Less well-known is that aldosterone potently alters mood, behavior, and appetite. It causes apathy, anhedonia, dysphoria, anorexia, and — most famously — salt hunger. Until recently, how and where aldosterone acts in the brain was the subject of controversy and confusion. To clarify where in the brain it acts, we searched the full brain for the two well-established molecular markers of cellular aldosterone-sensitivity: its receptor, MR (the mineralocorticoid receptor; Nr2c3) and the enzyme that “protects” its receptor from binding glucocorticoids, HSD2 (11-beta-hydroxysteroid dehydrogenase type 2; Hsd11b2). From mice to humans, the adult brain contains a one, small population of aldosterone-sensitive neurons, in the lower brainstem, forming a small, glutamatergic neuron subpopulation in the nucleus of the solitary tract (NTS). Recombinase-conditional labeling, in situ hybridization, immunofluorescence, MR translocation, and electrophysiologic recordings all point to the conclusion that these “HSD2 neurons” are selectively sensitive to aldosterone. The HSD2 neurons project axons from the NTS to sites implicated in mood, stress, and appetite control, not to brainstem regions that control autonomic reflexes. They activate in response to a variety of conditions that trigger sodium appetite — even in the absence of aldosterone — and consuming sodium inactivates them. Infusing aldosterone into the fourth ventricle, DREADD-activating HSD2 neurons, and activating their axon terminals in the bed nucleus of the stria terminalis all cause rodents to selectively increase salty food or fluid consumption, and to decrease consumption of non-salty food. HSD2 neurons also express Agtr1a and exhibit losartan-blockable spiking in response to angiotensin II in ex vivo slice recordings, suggesting they help mediate the aldosterone-angiotensin “synergy” that promotes sodium appetite. Our on-going work examines the down-stream neurons and circuits mediating aldosterone’s disparate effects on mood, sodium appetite, and hunger. We are also testing whether angiotensinogen in the brain or periphery is necessary for sodium appetite.