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PMID: 12657693 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Estrogen levels regulate the subcellular distribution of phosphorylated Akt in hippocampal CA1 dendrites.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 23 ·No. 6 ·2003-03-15 ·Pages 2340-7

Znamensky V, Akama KT, McEwen BS, Milner TA

Abstract

In addition to genomic pathways, estrogens may regulate gene expression by activating specific signal transduction pathways, such as that involving phosphatidylinositol 3-kinase (PI3-K) and the subsequent phosphorylation of Akt (protein kinase B). The Akt pathway regulates various cellular events, including the initiation of protein synthesis. Our previous studies showed that synaptogenesis in hippocampal CA1 pyramidal cell dendritic spines is highest when brain estrogen levels are highest. To address the role of Akt in this process, the subcellular distribution of phosphorylated Akt immunoreactivity (pAkt-I) in the hippocampus of female rats across the estrous cycle and male rats was analyzed by light microscopy (LM) and electron microscopy (EM). By LM, the density of pAkt-I in stratum radiatum of CA1 was significantly higher in proestrus rats (or in estrogen-supplemented ovariectomized females) compared with diestrus, estrus, or male rats. By EM, pAkt-I was found throughout the shafts and in select spines of stratum radiatum dendrites. Quantitative ultrastructural analysis identifying pAkt-I with immunogold particles revealed that proestrus rats compared with diestrus, estrus, and male rats contained significantly higher pAkt-I associated with (1) dendritic spines (both cytoplasm and plasmalemma), (2) spine apparati located within 0.1 microm of dendritic spine bases, (3) endoplasmic reticula and polyribosomes in the cytoplasm of dendritic shafts, and (4) the plasmalemma of dendritic shafts. These findings suggest that estrogens may regulate spine formation in CA1 pyramidal neurons via Akt-mediated signaling events.

MeSH Terms
Animals Dendrites/metabolism,ultrastructure Diestrus/metabolism Estradiol/analogs & derivatives,pharmacology Estrogens Estrus/metabolism Female Hippocampus/metabolism,ultrastructure Immunohistochemistry Male Microscopy, Electron Ovariectomy Phosphorylation Proestrus/metabolism Protein Serine-Threonine Kinases Proto-Oncogene Proteins/metabolism Proto-Oncogene Proteins c-akt Pyramidal Cells/metabolism,ultrastructure Rats Rats, Sprague-Dawley Sex Factors
Chemicals
Estrogens Proto-Oncogene Proteins estradiol 3-benzoate Estradiol Akt1 protein, rat Protein Serine-Threonine Kinases Proto-Oncogene Proteins c-akt
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Znamensky Vladimir
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, New York 10021, USA.
Akama Keith T
McEwen Bruce S
Milner Teresa A
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2003-03-15
Pages
2340-7
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6742003
Subset
IM
Grants
NIDA NIH HHS · DA08259 · United States
NIMH NIH HHS · MH12977 · United States
NIMH NIH HHS · F32 MH012977 · United States
NHLBI NIH HHS · P01 HL018974 · United States
NHLBI NIH HHS · HL18974 · United States
NIDA NIH HHS · R01 DA008259 · United States
NINDS NIH HHS · NS07080 · United States
NINDS NIH HHS · R01 NS007080 · United States
External Links
PubMed source PMC Full Text View journal details
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