Research Description:

Sodium facilitates vital processes in the body including growth, development, and extracellular fluid volume regulation, making it critical for survival. Due to sodium’s ability to regulate the extracellular fluid volume, and thus impact cardiovascular function, its intake and excretion are tightly regulated by aldosterone, the primary mineralocorticoid steroid hormone. In the kidney, aldosterone decreases sodium excretion through transcriptional changes activated by binding to the mineralocorticoid receptor (MR). In the brain, aldosterone induces sodium intake by activating NTS^HSD2 neurons, the only aldosterone-sensitive population within the adult mouse brain due to their coexpression of MR and 11b-hydroxysteroid dehydrogenase type 2 (HSD2), which reduces competition for MR. NTS^HSD2 neurons are necessary and sufficient for aldosterone-mediated sodium appetite – the behavioral drive to find and ingest sodium. 

Currently, we know that HSD2 neurons are activated by chronic aldosterone treatment which ultimately increases the firing rate of NTS^HSD2 neurons. However, the mechanism by which aldosterone activates NTS^HSD2 neurons is unknown.  In order to understand how aldosterone impacts NTS^HSD2 neuron function, I am using fiber photometry to visualize NTS^HSD2 neuron activation in response to aldosterone treatment, both acute and chronic. In addition, I will use multiomic snRNA/ATAC sequencing of NTS^HSD2 neurons during aldosterone treatment. With the sequencing data, we will identify the genes differentially regulated by aldosterone-MR that could mediate increased neuronal firing. Understanding the regulation of NTS^HSD2 neuron activity by both aldosterone-dependent and independent mechanisms is key for future investigation of the role of NTS^HSD2 neurons in sodium appetite.

Awards:

• Ruth L. Kirschstein National Research Service Award (NRSA) Individual Fellowship (NIH F31 HL170784), 2024-2027
• Predoctoral Training Grant in the Pharmacological Sciences Training Program (NIH T32 GM144636), 2022-2023
• Fellowship appointment on the Pharmacological Sciences Training Program (NIH T32 GM067795), University of Iowa, 2021-2022

Publications:

• Laule C, Guo DF, Zhao Y, Williams PA, Morgan DA, Rouabhi Y, McDonough M, Butler T, Resch J, Rahmouni K. The brainstem BBSome regulates glucose homeostasis and lean mass in a state-dependent manner. Mol Metab 100:102222, 2025. PMCID: PMC12361606
• Andrianov YE, Keyes AL, Warwick CA, McDonough MC, Shutov LP, Solanki KS, Resch JM, Bassuk AG, Voitenko N, Belan P, Usachev YM. Activation of TRPA1 and TRPM3 triggers Ca²⁺ waves in central terminals of sensory neurons and facilitates synaptic activity in the spinal dorsal horn. J Physiol 2025 Apr 2. doi: 10.1113/JP286407.  PMID: 40172079
• Kuralay A, McDonough MC, Resch JM. Control of sodium appetite by hindbrain aldosterone-sensitive neurons. Mol Cell Endocrinol 1:592:112323.  PMCID: PMC11381173.  (Review)
• Bahl E, Chatterjee S, Mukherjee U, Elsadany M, Vanrobaeys Y, Lin LC, McDonough M, Resch J, Giese KP, Abel T, Michaelson JJ. Using deep learning to quantify neuronal activation from single-cell and spatial transcriptomic data. Nat Commun 15(1):779, 2024.  PMCID: PMC10817898
• Gasparini S, Peltekian L, McDonough MC, Mitchell CJ, Hefti M, Resch JM, Geerling JC. Aldosterone-induced salt appetite requires HSD2 neurons. JCI Insight 9(23):e175087, 2024.  PMCID: PMC11623954