Aldosterone-induced salt appetite requires HSD2 neurons

Silvia Gasparini; Lila Peltekian; Miriam C. McDonough; Chidera J.A. Mitchell; Marco Hefti; Jon M. Resch; Joel C. Geerling

doi:10.1172/jci.insight.175087

Aldosterone-induced salt appetite requires HSD2 neurons

Silvia Gasparini,¹ Lila Peltekian,¹ Miriam C. McDonough,² Chidera J.A. Mitchell,¹ Marco Hefti,³ Jon M. Resch,² and Joel C. Geerling¹

Published October 24, 2024 - More info

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Abstract

Excessive aldosterone production increases the risk of heart disease, stroke, dementia, and death. Aldosterone increases both sodium retention and sodium consumption, and increased sodium consumption may worsen end-organ damage in patients with aldosteronism. Preventing this increase could improve outcomes, but the behavioral mechanisms of aldosterone-induced sodium appetite remain unclear. In rodents, we previously identified aldosterone-sensitive neurons, which express the mineralocorticoid receptor and its pre-receptor regulator, 11-beta-hydroxysteroid dehydrogenase 2 (HSD2). In the present study, we identified HSD2 neurons in the human brain, then used a mouse model to evaluate their role in aldosterone-induced salt intake. First, we confirmed that dietary sodium deprivation increases aldosterone production, salt intake, and HSD2 neuron activity. Next, we showed that continuous chemogenetic stimulation of HSD2 neurons causes a large and specific increase in salt intake. Finally, we use dose-response studies and genetically targeted ablation of HSD2 neurons to show that these neurons are necessary for aldosterone-induced salt intake. Identifying HSD2 neurons in the human brain and establishing their necessity for aldosterone-induced salt intake in mice improves our understanding of appetitive circuits and highlights this small cell population as a therapeutic target for moderating dietary sodium.

Aldosterone-induced salt appetite requires HSD2 neurons

Silvia Gasparini,¹ Lila Peltekian,¹ Miriam C. McDonough,² Chidera J.A. Mitchell,¹ Marco Hefti,³ Jon M. Resch,² and Joel C. Geerling¹

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Aldosterone-induced salt appetite requires HSD2 neurons

Silvia Gasparini,1 Lila Peltekian,1 Miriam C. McDonough,2 Chidera J.A. Mitchell,1 Marco Hefti,3 Jon M. Resch,2 and Joel C. Geerling1

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Silvia Gasparini,¹ Lila Peltekian,¹ Miriam C. McDonough,² Chidera J.A. Mitchell,¹ Marco Hefti,³ Jon M. Resch,² and Joel C. Geerling¹