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Redistribution of NMDA Receptors in Estrogen-Receptor-β-Containing Paraventricular Hypothalamic Neurons following Slow-Pressor Angiotensin II Hypertension in Female Mice with Accelerated Ovarian Failure.

TitleRedistribution of NMDA Receptors in Estrogen-Receptor-β-Containing Paraventricular Hypothalamic Neurons following Slow-Pressor Angiotensin II Hypertension in Female Mice with Accelerated Ovarian Failure.
Publication TypeJournal Article
Year of Publication2017
AuthorsMarques-Lopes J, Tesfaye E, Israilov S, Van Kempen TA, Wang G, Glass MJ, Pickel VM, Iadecola C, Waters EM, Milner TA
JournalNeuroendocrinology
Volume104
Issue3
Pagination239-256
Date Published2017
ISSN1423-0194
KeywordsAngiotensin II, Animals, Blood Pressure, Cyclohexenes, Disease Models, Animal, Estrous Cycle, Female, Green Fluorescent Proteins, Hypertension, Mice, Mice, Inbred C57BL, Mice, Transgenic, Microscopy, Immunoelectron, Nerve Tissue Proteins, Neurons, Ovarian Diseases, Paraventricular Hypothalamic Nucleus, Reactive Oxygen Species, Receptors, Estrogen, Receptors, N-Methyl-D-Aspartate, Vinyl Compounds
Abstract

Hypertension in male and aging female rodents is associated with glutamate-dependent plasticity in the hypothalamus, but existing models have failed to capture distinct transitional menopausal phases that could have a significant impact on the synaptic plasticity and emergent hypertension. In rodents, accelerated ovarian failure (AOF) induced by systemic injection of 4-vinylcyclohexane diepoxide mimics the estrogen fluctuations seen in human menopause including the perimenopause transition (peri-AOF) and postmenopause (post-AOF). Thus, we used the mouse AOF model to determine the impact of slow-pressor angiotensin II (AngII) administration on blood pressure and on the subcellular distribution of obligatory N-methyl-D-aspartate (NMDA) receptor GluN1 subunits in the paraventricular hypothalamic nucleus (PVN), a key estrogen-responsive cardiovascular regulatory area. Estrogen-sensitive neuronal profiles were identified in mice expressing enhanced green fluorescent protein under the promoter for estrogen receptor (ER) β, a major ER in the PVN. Slow-pressor AngII increased arterial blood pressure in mice at peri- and post-AOF time points. In control oil-injected (nonhypertensive) mice, AngII decreased the total number of GluN1 in ERβ-containing PVN dendrites. In contrast, AngII resulted in a reapportionment of GluN1 from the cytoplasm to the plasma membrane of ERβ-containing PVN dendrites in peri-AOF mice. Moreover, in post-AOF mice, AngII increased total GluN1, dendritic size and radical production in ERβ-containing neurons. These results indicate that unique patterns of hypothalamic glutamate receptor plasticity and dendritic structure accompany the elevated blood pressure in peri- and post-AOF time points. Our findings suggest the possibility that distinct neurobiological processes are associated with the increased blood pressure during perimenopausal and postmenopausal periods.

DOI10.1159/000446073
Alternate JournalNeuroendocrinology
PubMed ID27078860
PubMed Central IDPMC5381723
Grant ListT32 DA007274 / DA / NIDA NIH HHS / United States
R01 DA008259 / DA / NIDA NIH HHS / United States
R01 HL098351 / HL / NHLBI NIH HHS / United States
P01 AG016765 / AG / NIA NIH HHS / United States
R37 NS089323 / NS / NINDS NIH HHS / United States
P01 HL096571 / HL / NHLBI NIH HHS / United States