Hippocampal dynorphin immunoreactivity increases in response to gonadal steroids and is positioned for direct modulation by ovarian steroid receptors

A. Torres-Reveron, S. Khalid, Tanya McDonald, E. M. Waters, L. Jacome, V. N. Luine, C. T. Drake, B. S. McEwen, T. A. Milner

Research output: Contribution to journalArticle

Abstract

The hippocampal formation (HF) is involved in modulating learning related to drug abuse. While HF-dependent learning is regulated by both endogenous opioids and estrogen, the interaction between these two systems is not well understood. The mossy fiber (MF) pathway formed by dentate gyrus (DG) granule cell axons is involved in some aspects of learning and contains abundant amounts of the endogenous opioid peptide dynorphin (DYN). To examine the influence of ovarian steroids on DYN expression, we used quantitative light microscopic immunocytochemistry to measure DYN levels in normal cycling rats as well as in two established models of hormone-treated ovariectomized (OVX) rats. Rats in estrus had increased levels of DYN-immunoreactivity (ir) in the DG and certain CA3 lamina compared with rats in proestrus or diestrus. OVX rats exposed to estradiol for 24 h showed increased DYN-ir in the DG and CA3, while those with 72 h estradiol exposure showed increases only in the DG. Six hours of estradiol exposure produced no change in DYN-ir. OVX rats chronically implanted with medroxyprogesterone also showed increased DYN-ir in the DG and CA3. Next, dual-labeling electron microscopy (EM) was used to evaluate the subcellular relationships of estrogen receptor (ER) α-, ERβ and progestin receptor (PR) with DYN-labeled MFs. ERβ-ir was in some DYN-labeled MF terminals and smaller terminals, and had a subcellular association with the plasmalemma and small synaptic vesicles. In contrast, ERα-ir was not in DYN-labeled terminals, although some DYN-labeled small terminals synapsed on ERα-labeled dendritic spines. PR labeling was mostly in CA3 axons, some of which were continuous with DYN-labeled terminals. These studies indicate that ovarian hormones can modulate DYN in the MF pathway in a time-dependent manner, and suggest that hormonal effects on the DYN-containing MF pathway may be directly mediated by ERβ and/or PR activation.

Original languageEnglish (US)
Pages (from-to)204-216
Number of pages13
JournalNeuroscience
Volume159
Issue number1
DOIs
StatePublished - Mar 3 2009
Externally publishedYes

Fingerprint

Dynorphins
Steroid Receptors
Steroids
Estrogen Receptors
Dentate Gyrus
Progesterone Receptors
Estradiol
Learning
Axons
Hippocampus
Medroxyprogesterone
Hormones
Diestrus
Proestrus
Dendritic Spines
Opioid Peptides
Synaptic Vesicles
Estrus
Opioid Analgesics

Keywords

  • CA3
  • dentate gyrus
  • estrogen
  • estrous cycle
  • opioid
  • progestin

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Hippocampal dynorphin immunoreactivity increases in response to gonadal steroids and is positioned for direct modulation by ovarian steroid receptors. / Torres-Reveron, A.; Khalid, S.; McDonald, Tanya; Waters, E. M.; Jacome, L.; Luine, V. N.; Drake, C. T.; McEwen, B. S.; Milner, T. A.

In: Neuroscience, Vol. 159, No. 1, 03.03.2009, p. 204-216.

Research output: Contribution to journalArticle

Torres-Reveron, A. ; Khalid, S. ; McDonald, Tanya ; Waters, E. M. ; Jacome, L. ; Luine, V. N. ; Drake, C. T. ; McEwen, B. S. ; Milner, T. A. / Hippocampal dynorphin immunoreactivity increases in response to gonadal steroids and is positioned for direct modulation by ovarian steroid receptors. In: Neuroscience. 2009 ; Vol. 159, No. 1. pp. 204-216.
@article{d4f0b8808eab4afabcc3324b182bad35,
title = "Hippocampal dynorphin immunoreactivity increases in response to gonadal steroids and is positioned for direct modulation by ovarian steroid receptors",
abstract = "The hippocampal formation (HF) is involved in modulating learning related to drug abuse. While HF-dependent learning is regulated by both endogenous opioids and estrogen, the interaction between these two systems is not well understood. The mossy fiber (MF) pathway formed by dentate gyrus (DG) granule cell axons is involved in some aspects of learning and contains abundant amounts of the endogenous opioid peptide dynorphin (DYN). To examine the influence of ovarian steroids on DYN expression, we used quantitative light microscopic immunocytochemistry to measure DYN levels in normal cycling rats as well as in two established models of hormone-treated ovariectomized (OVX) rats. Rats in estrus had increased levels of DYN-immunoreactivity (ir) in the DG and certain CA3 lamina compared with rats in proestrus or diestrus. OVX rats exposed to estradiol for 24 h showed increased DYN-ir in the DG and CA3, while those with 72 h estradiol exposure showed increases only in the DG. Six hours of estradiol exposure produced no change in DYN-ir. OVX rats chronically implanted with medroxyprogesterone also showed increased DYN-ir in the DG and CA3. Next, dual-labeling electron microscopy (EM) was used to evaluate the subcellular relationships of estrogen receptor (ER) α-, ERβ and progestin receptor (PR) with DYN-labeled MFs. ERβ-ir was in some DYN-labeled MF terminals and smaller terminals, and had a subcellular association with the plasmalemma and small synaptic vesicles. In contrast, ERα-ir was not in DYN-labeled terminals, although some DYN-labeled small terminals synapsed on ERα-labeled dendritic spines. PR labeling was mostly in CA3 axons, some of which were continuous with DYN-labeled terminals. These studies indicate that ovarian hormones can modulate DYN in the MF pathway in a time-dependent manner, and suggest that hormonal effects on the DYN-containing MF pathway may be directly mediated by ERβ and/or PR activation.",
keywords = "CA3, dentate gyrus, estrogen, estrous cycle, opioid, progestin",
author = "A. Torres-Reveron and S. Khalid and Tanya McDonald and Waters, {E. M.} and L. Jacome and Luine, {V. N.} and Drake, {C. T.} and McEwen, {B. S.} and Milner, {T. A.}",
year = "2009",
month = "3",
day = "3",
doi = "10.1016/j.neuroscience.2008.12.023",
language = "English (US)",
volume = "159",
pages = "204--216",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "1",

}

TY - JOUR

T1 - Hippocampal dynorphin immunoreactivity increases in response to gonadal steroids and is positioned for direct modulation by ovarian steroid receptors

AU - Torres-Reveron, A.

AU - Khalid, S.

AU - McDonald, Tanya

AU - Waters, E. M.

AU - Jacome, L.

AU - Luine, V. N.

AU - Drake, C. T.

AU - McEwen, B. S.

AU - Milner, T. A.

PY - 2009/3/3

Y1 - 2009/3/3

N2 - The hippocampal formation (HF) is involved in modulating learning related to drug abuse. While HF-dependent learning is regulated by both endogenous opioids and estrogen, the interaction between these two systems is not well understood. The mossy fiber (MF) pathway formed by dentate gyrus (DG) granule cell axons is involved in some aspects of learning and contains abundant amounts of the endogenous opioid peptide dynorphin (DYN). To examine the influence of ovarian steroids on DYN expression, we used quantitative light microscopic immunocytochemistry to measure DYN levels in normal cycling rats as well as in two established models of hormone-treated ovariectomized (OVX) rats. Rats in estrus had increased levels of DYN-immunoreactivity (ir) in the DG and certain CA3 lamina compared with rats in proestrus or diestrus. OVX rats exposed to estradiol for 24 h showed increased DYN-ir in the DG and CA3, while those with 72 h estradiol exposure showed increases only in the DG. Six hours of estradiol exposure produced no change in DYN-ir. OVX rats chronically implanted with medroxyprogesterone also showed increased DYN-ir in the DG and CA3. Next, dual-labeling electron microscopy (EM) was used to evaluate the subcellular relationships of estrogen receptor (ER) α-, ERβ and progestin receptor (PR) with DYN-labeled MFs. ERβ-ir was in some DYN-labeled MF terminals and smaller terminals, and had a subcellular association with the plasmalemma and small synaptic vesicles. In contrast, ERα-ir was not in DYN-labeled terminals, although some DYN-labeled small terminals synapsed on ERα-labeled dendritic spines. PR labeling was mostly in CA3 axons, some of which were continuous with DYN-labeled terminals. These studies indicate that ovarian hormones can modulate DYN in the MF pathway in a time-dependent manner, and suggest that hormonal effects on the DYN-containing MF pathway may be directly mediated by ERβ and/or PR activation.

AB - The hippocampal formation (HF) is involved in modulating learning related to drug abuse. While HF-dependent learning is regulated by both endogenous opioids and estrogen, the interaction between these two systems is not well understood. The mossy fiber (MF) pathway formed by dentate gyrus (DG) granule cell axons is involved in some aspects of learning and contains abundant amounts of the endogenous opioid peptide dynorphin (DYN). To examine the influence of ovarian steroids on DYN expression, we used quantitative light microscopic immunocytochemistry to measure DYN levels in normal cycling rats as well as in two established models of hormone-treated ovariectomized (OVX) rats. Rats in estrus had increased levels of DYN-immunoreactivity (ir) in the DG and certain CA3 lamina compared with rats in proestrus or diestrus. OVX rats exposed to estradiol for 24 h showed increased DYN-ir in the DG and CA3, while those with 72 h estradiol exposure showed increases only in the DG. Six hours of estradiol exposure produced no change in DYN-ir. OVX rats chronically implanted with medroxyprogesterone also showed increased DYN-ir in the DG and CA3. Next, dual-labeling electron microscopy (EM) was used to evaluate the subcellular relationships of estrogen receptor (ER) α-, ERβ and progestin receptor (PR) with DYN-labeled MFs. ERβ-ir was in some DYN-labeled MF terminals and smaller terminals, and had a subcellular association with the plasmalemma and small synaptic vesicles. In contrast, ERα-ir was not in DYN-labeled terminals, although some DYN-labeled small terminals synapsed on ERα-labeled dendritic spines. PR labeling was mostly in CA3 axons, some of which were continuous with DYN-labeled terminals. These studies indicate that ovarian hormones can modulate DYN in the MF pathway in a time-dependent manner, and suggest that hormonal effects on the DYN-containing MF pathway may be directly mediated by ERβ and/or PR activation.

KW - CA3

KW - dentate gyrus

KW - estrogen

KW - estrous cycle

KW - opioid

KW - progestin

UR - http://www.scopus.com/inward/record.url?scp=60349093588&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=60349093588&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2008.12.023

DO - 10.1016/j.neuroscience.2008.12.023

M3 - Article

C2 - 19150393

AN - SCOPUS:60349093588

VL - 159

SP - 204

EP - 216

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 1

ER -