Supplementary Material for: 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
<p>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.</p