Effects of estrogen and aging on synaptic morphology and distribution of phosphorylated Tyr1472 NR2B in the female rat hippocampus

Elizabeth M. Waters, Sanoara Mazid, Mariana Dodos, Rishi Puri, William G. Janssen, John Morrison, Bruce S. McEwen, Teresa A. Milner

Research output: Contribution to journalArticle

Abstract

Age and estrogens may impact the mobility of N-methyl-D-aspartate receptors (NMDARs) in hippocampal synapses. Here, we used serial section immunogold electron microscopy to examine whether phosphorylated tyrosine 1472 NR2B (pY1472), which is involved in the surface expression of NMDARs, is altered in the dorsal hippocampus of young (3–4 months old) and aged (∼24 months old) ovariectomized rats treated with 17β-estradiol or vehicle for 2 days. The number of gold particles labeling pY1472 was higher in presynaptic and postsynaptic compartments of aged rats with low estradiol (vehicle-treated) compared to other groups. In terminals, pY1472 levels were elevated in aged rats but reduced by estradiol treatment to levels seen in young rats. Conversely, the mitochondria number was lower in aged females but was restored to young levels by estradiol. In the postsynaptic density and dendritic spines, estradiol reduced pY1472 in young and aged rats. As phosphorylation at Y1472 blocks NR2B endocytosis, reduction of pY1472 by estradiol suggests another mechanism through which estrogen enhances synaptic plasticity by altering localization of NMDAR subunits within synapses.

LanguageEnglish (US)
Pages200-210
Number of pages11
JournalNeurobiology of Aging
Volume73
DOIs
StatePublished - Jan 1 2019

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Estradiol
Hippocampus
Estrogens
N-Methyl-D-Aspartate Receptors
Synapses
Post-Synaptic Density
Dendritic Spines
Neuronal Plasticity
Endocytosis
Gold
Tyrosine
Electron Microscopy
Mitochondria
Phosphorylation

Keywords

  • Aging
  • CA1 region
  • Estrogen deprivation
  • Hormone replacement
  • Presynaptic glutamate receptors

ASJC Scopus subject areas

  • Neuroscience(all)
  • Aging
  • Clinical Neurology
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Effects of estrogen and aging on synaptic morphology and distribution of phosphorylated Tyr1472 NR2B in the female rat hippocampus. / Waters, Elizabeth M.; Mazid, Sanoara; Dodos, Mariana; Puri, Rishi; Janssen, William G.; Morrison, John; McEwen, Bruce S.; Milner, Teresa A.

In: Neurobiology of Aging, Vol. 73, 01.01.2019, p. 200-210.

Research output: Contribution to journalArticle

Waters, Elizabeth M. ; Mazid, Sanoara ; Dodos, Mariana ; Puri, Rishi ; Janssen, William G. ; Morrison, John ; McEwen, Bruce S. ; Milner, Teresa A. / Effects of estrogen and aging on synaptic morphology and distribution of phosphorylated Tyr1472 NR2B in the female rat hippocampus. In: Neurobiology of Aging. 2019 ; Vol. 73. pp. 200-210.
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