Estrogen levels regulate the subcellular distribution of phosphorylated Akt in hippocampal CA1 dendrites. Academic Article uri icon

Overview

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.

publication date

  • March 15, 2003

Research

keywords

  • Dendrites
  • Estradiol
  • Estrogens
  • Hippocampus
  • Protein Serine-Threonine Kinases
  • Proto-Oncogene Proteins

Identity

PubMed Central ID

  • PMC6742003

Scopus Document Identifier

  • 0037444650

Digital Object Identifier (DOI)

  • 10.1523/JNEUROSCI.23-06-02340.2003

PubMed ID

  • 12657693

Additional Document Info

volume

  • 23

issue

  • 6