Journal article
Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertension
Frontiers in cellular neuroscience, Vol.17, 1207350
05/24/2023
DOI: 10.3389/fncel.2023.1207350
PMCID: PMC10244568
PMID: 37293629
Abstract
A common preclinical model of hypertension characterized by low circulating renin is the “deoxycorticosterone acetate (DOCA)-salt” model, which influences blood pressure and metabolism through mechanisms involving the angiotensin II type 1 receptor (AT1R) in the brain. More specifically, AT1R within Agouti-related peptide (AgRP) neurons of the arcuate nucleus of the hypothalamus (ARC) has been implicated in selected effects of DOCA-salt. In addition, microglia have been implicated in the cerebrovascular effects of DOCA-salt and angiotensin II. To characterize DOCA-salt effects upon the transcriptomes of individual cell types within the ARC, we used single-nucleus RNA sequencing (snRNAseq) to examine this region from male C57BL/6J mice that underwent sham or DOCA-salt treatment. Thirty-two unique primary cell type clusters were identified. Sub-clustering of neuropeptide-related clusters resulted in identification of three distinct AgRP subclusters. DOCA-salt treatment caused subtype-specific changes in gene expression patterns associated with AT1R and G protein signaling, neurotransmitter uptake, synapse functions, and hormone secretion. In addition, two primary cell type clusters were identified as resting versus activated microglia, and multiple distinct subtypes of activated microglia were suggested by sub-cluster analysis. While DOCA-salt had no overall effect on total microglial density within the ARC, DOCA-salt appeared to cause a redistribution of the relative abundance of activated microglia subtypes. These data provide novel insights into cell-specific molecular changes occurring within the ARC during DOCA-salt treatment, and prompt increased investigation of the physiological & pathophysiological significance of distinct subtypes of neuronal and glial cell types.
Details
- Title: Subtitle
- Cell-specific transcriptome changes in the hypothalamic arcuate nucleus in a mouse deoxycorticosterone acetate-salt model of hypertension
- Creators
- Valerie WagnerGuorui DengKristin ClaflinMcKenzie RitterHuxing CuiPablo NakagawaCurt SigmundLisa MorselliJustin GrobeAnne Kwitek
- Resource Type
- Journal article
- Publication Details
- Frontiers in cellular neuroscience, Vol.17, 1207350
- DOI
- 10.3389/fncel.2023.1207350
- PMID
- 37293629
- PMCID
- PMC10244568
- NLM abbreviation
- Front Cell Neurosci
- ISSN
- 1662-5102
- eISSN
- 1662-5102
- Publisher
- Frontiers Research Foundation
- Language
- English
- Date published
- 05/24/2023
- Academic Unit
- Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology
- Record Identifier
- 9984419454302771
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