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Sex differences in NMDA GluN1 plasticity in rostral ventrolateral medulla neurons containing corticotropin-releasing factor type 1 receptor following slow-pressor angiotensin II hypertension.

TitleSex differences in NMDA GluN1 plasticity in rostral ventrolateral medulla neurons containing corticotropin-releasing factor type 1 receptor following slow-pressor angiotensin II hypertension.
Publication TypeJournal Article
Year of Publication2015
AuthorsVan Kempen TA, Dodos M, Woods C, Marques-Lopes J, Justice NJ, Iadecola C, Pickel VM, Glass MJ, Milner TA
JournalNeuroscience
Volume307
Pagination83-97
Date Published2015 Oct 29
ISSN1873-7544
KeywordsAngiotensin II, Animals, Disease Models, Animal, Female, Gene Expression Regulation, Green Fluorescent Proteins, Hypertension, Male, Medulla Oblongata, Mice, Mice, Transgenic, Microscopy, Immunoelectron, Nerve Tissue Proteins, Neuronal Plasticity, Neurons, Receptors, Corticotropin-Releasing Hormone, Receptors, N-Methyl-D-Aspartate, RNA, Messenger, Sex Characteristics, Stilbamidines, Subcellular Fractions, Tyrosine 3-Monooxygenase
Abstract

There are profound, yet incompletely understood, sex differences in the neurogenic regulation of blood pressure. Both corticotropin signaling and glutamate receptor plasticity, which differ between males and females, are known to play important roles in the neural regulation of blood pressure. However, the relationship between hypertension and glutamate plasticity in corticotropin-releasing factor (CRF)-receptive neurons in brain cardiovascular regulatory areas, including the rostral ventrolateral medulla (RVLM) and paraventricular nucleus of the hypothalamus (PVN), is not understood. In the present study, we used dual-label immuno-electron microscopy to analyze sex differences in slow-pressor angiotensin II (AngII) hypertension with respect to the subcellular distribution of the obligatory NMDA glutamate receptor subunit 1 (GluN1) subunit of the N-methyl-D-aspartate receptor (NMDAR) in the RVLM and PVN. Studies were conducted in mice expressing the enhanced green fluorescence protein (EGFP) under the control of the CRF type 1 receptor (CRF1) promoter (i.e., CRF1-EGFP reporter mice). By light microscopy, GluN1-immunoreactivity (ir) was found in CRF1-EGFP neurons of the RVLM and PVN. Moreover, in both regions tyrosine hydroxylase (TH) was found in CRF1-EGFP neurons. In response to AngII, male mice showed an elevation in blood pressure that was associated with an increase in the proportion of GluN1 on presumably functional areas of the plasma membrane (PM) in CRF1-EGFP dendritic profiles in the RVLM. In female mice, AngII was neither associated with an increase in blood pressure nor an increase in PM GluN1 in the RVLM. Unlike the RVLM, AngII-mediated hypertension had no effect on GluN1 localization in CRF1-EGFP dendrites in the PVN of either male or female mice. These studies provide an anatomical mechanism for sex-differences in the convergent modulation of RVLM catecholaminergic neurons by CRF and glutamate. Moreover, these results suggest that sexual dimorphism in AngII-induced hypertension is reflected by NMDA receptor trafficking in presumptive sympathoexcitatory neurons in the RVLM.

DOI10.1016/j.neuroscience.2015.08.029
Alternate JournalNeuroscience
PubMed ID26306872
PubMed Central IDPMC4591238
Grant ListDA08259 / DA / NIDA NIH HHS / United States
HL096571 / HL / NHLBI NIH HHS / United States
T32 DA007274 / DA / NIDA NIH HHS / United States
R01 DA008259 / DA / NIDA NIH HHS / United States
R01 HL098351 / HL / NHLBI NIH HHS / United States
DA007274 / DA / NIDA NIH HHS / United States
HL098351 / HL / NHLBI NIH HHS / United States
P01 HL096571 / HL / NHLBI NIH HHS / United States
R01 DA024030 / DA / NIDA NIH HHS / United States