Aldosterone-sensitive HSD2 neurons in mice

Silvia Gasparini; Jon M Resch; Sowmya V Narayan; Lila Peltekian; Gabrielle N Iverson; Samyukta Karthik; Joel C Geerling

doi:10.1007/s00429-018-1778-y

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Aldosterone-sensitive HSD2 neurons in mice

Journal article

Peer reviewed

Aldosterone-sensitive HSD2 neurons in mice

Silvia Gasparini, Jon M Resch, Sowmya V Narayan, Lila Peltekian, Gabrielle N Iverson, Samyukta Karthik and Joel C Geerling

Brain structure & function, Vol.224(1), pp.387-417

01/2019

DOI: 10.1007/s00429-018-1778-y

PMCID: PMC6369013

PMID: 30343334

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Abstract

Sodium deficiency elevates aldosterone, which in addition to epithelial tissues acts on the brain to promote dysphoric symptoms and salt intake. Aldosterone boosts the activity of neurons that express 11-beta-hydroxysteroid dehydrogenase type 2 (HSD2), a hallmark of aldosterone-sensitive cells. To better characterize these neurons, we combine immunolabeling and in situ hybridization with fate mapping and Cre-conditional axon tracing in mice. Many cells throughout the brain have a developmental history of Hsd11b2 expression, but in the adult brain one small brainstem region with a leaky blood-brain barrier contains HSD2 neurons. These neurons express Hsd11b2, Nr3c2 (mineralocorticoid receptor), Agtr1a (angiotensin receptor), Slc17a6 (vesicular glutamate transporter 2), Phox2b, and Nxph4; many also express Cartpt or Lmx1b. No HSD2 neurons express cholinergic, monoaminergic, or several other neuropeptidergic markers. Their axons project to the parabrachial complex (PB), where they intermingle with AgRP-immunoreactive axons to form dense terminal fields overlapping FoxP2 neurons in the central lateral subnucleus (PBcL) and pre-locus coeruleus (pLC). Their axons also extend to the forebrain, intermingling with AgRP- and CGRP-immunoreactive axons to form dense terminals surrounding GABAergic neurons in the ventrolateral bed nucleus of the stria terminalis (BSTvL). Sparse axons target the periaqueductal gray, ventral tegmental area, lateral hypothalamic area, paraventricular hypothalamic nucleus, and central nucleus of the amygdala. Dual retrograde tracing revealed that largely separate HSD2 neurons project to pLC/PB or BSTvL. This projection pattern raises the possibility that a subset of HSD2 neurons promotes the dysphoric, anorexic, and anhedonic symptoms of hyperaldosteronism via AgRP-inhibited relay neurons in PB.

Neural Pathways - enzymology

Axons - enzymology

Neural Pathways - drug effects

Enkephalins - metabolism

Neuroanatomical Tract-Tracing Techniques

Male

Solitary Nucleus - enzymology

Brain Stem - cytology

Brain Stem - drug effects

Prosencephalon - enzymology

Prosencephalon - drug effects

Enkephalins - genetics

Brain Stem - enzymology

Receptor, Angiotensin, Type 1 - genetics

Appetite Regulation

11-beta-Hydroxysteroid Dehydrogenase Type 2 - genetics

Neurons - drug effects

Genes, Reporter

Solitary Nucleus - cytology

Protein Precursors - genetics

Mice, Inbred C57BL

Gene Expression Regulation

Axons - drug effects

Aldosterone - pharmacology

Feeding Behavior

In Situ Hybridization, Fluorescence

Mice, Transgenic

Solitary Nucleus - drug effects

Protein Precursors - metabolism

Animals

Prosencephalon - cytology

Neurons - enzymology

Receptor, Angiotensin, Type 1 - metabolism

11-beta-Hydroxysteroid Dehydrogenase Type 2 - metabolism

Fluorescent Antibody Technique

Luminescent Proteins - genetics

Microscopy, Fluorescence

Luminescent Proteins - metabolism

Details

Title: Subtitle: Aldosterone-sensitive HSD2 neurons in mice
Creators: Silvia Gasparini - Department of Neurology, University of Iowa, PBDB 1320, 169 Newton Rd., Iowa City, IA, 52246, USA
Jon M Resch - Department of Medicine, Beth Israel Deaconess Medical Center, Boston, USA
Sowmya V Narayan - Department of Neurology, University of Iowa, PBDB 1320, 169 Newton Rd., Iowa City, IA, 52246, USA
Lila Peltekian - Department of Neurology, University of Iowa, PBDB 1320, 169 Newton Rd., Iowa City, IA, 52246, USA
Gabrielle N Iverson - Department of Neurology, University of Iowa, PBDB 1320, 169 Newton Rd., Iowa City, IA, 52246, USA
Samyukta Karthik - Department of Neurology, University of Iowa, PBDB 1320, 169 Newton Rd., Iowa City, IA, 52246, USA
Joel C Geerling - Department of Neurology, University of Iowa, PBDB 1320, 169 Newton Rd., Iowa City, IA, 52246, USA. joel-geerling@uiowa.edu
Resource Type: Journal article
Publication Details: Brain structure & function, Vol.224(1), pp.387-417
DOI: 10.1007/s00429-018-1778-y
PMID: 30343334
PMCID: PMC6369013
NLM abbreviation: Brain Struct Funct
ISSN: 1863-2653
eISSN: 1863-2661
Publisher: Germany
Grant note: K08 NS099425 / NINDS NIH HHS JG2017 / Aging Mind and Brain Institute, University of Iowa Center on Aging F32 DK103387 / National Institute of Diabetes and Digestive and Kidney Diseases F32 DK103387 / NIDDK NIH HHS NS099425 / National Institute of Neurological Disorders and Stroke (US)
Language: English
Date published: 01/2019
Academic Unit: Neurology; Iowa Neuroscience Institute; Neuroscience and Pharmacology
Record Identifier: 9984016645502771

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