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PMID: 18691558 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Ovarian steroids modulate leu-enkephalin levels and target leu-enkephalinergic profiles in the female hippocampal mossy fiber pathway.

Brain research ·Vol. 1232 ·2008-09-26 ·Pages 70-84

Torres-Reveron A, Khalid S, Williams TJ, Waters EM, Drake CT, McEwen BS, Milner TA

Abstract

In the hippocampal formation (HF), the enkephalin opioids and estrogen are each known to modulate learning and cognitive performance relevant to drug abuse. Within the HF, leu-enkephalin (LENK) is most prominent in the mossy fiber (MF) pathway formed by the axons of dentate gyrus (DG) granule cells. To examine the influence of ovarian steroids on MF pathway LENK levels, we used quantitative light microscopic immunocytochemistry to evaluate LENK levels in normal cycling rats and in estrogen-treated ovariectomized rats. Rats in estrus had increased levels of LENK-immunoreactivity (ir) in the DG hilus compared to rats in diestrus or proestrus. Rats in estrus and proestrus had higher levels of LENK-ir in CA3a-c compared to rats in diestrus. Ovariectomized (OVX) rats 24 h (but not 6 or 72 h) after estradiol benzoate (EB; 10 microg) administration had increased LENK-ir in the DG hilus and CA3c. Electron microscopy showed a larger proportion of LENK-labeled small terminals and axons in the DG hilus compared to CA3 which may have contributed to region-specific changes in LENK-ir densities. Next we evaluated the subcellular relationships of estrogen receptor (ER) alpha, ERbeta and progestin receptor (PR) with LENK-labeled MF pathway profiles using dual-labeling electron microscopy. ERbeta-ir colocalized in some LENK-labeled MF terminals and smaller terminals while PR-ir was mostly in CA3 axons, some of which also showed colocalization with LENK. ERalpha-ir was in dendritic spines, but no colocalization with LENK-labeled profiles was observed. The present studies indicate that estrogen can modulate LENK in subregions of the MF pathway in a dose-and time-dependent manner. These effects might be triggered by direct activation of ERbeta or PR in LENK-containing terminals.

MeSH Terms
Animals Densitometry Enkephalin, Leucine/metabolism Estrogen Receptor alpha/metabolism Estrogen Receptor beta/metabolism Estrogens/pharmacology Female Ganglia, Spinal/drug effects,metabolism Immunochemistry Immunohistochemistry Microscopy, Immunoelectron Mossy Fibers, Hippocampal/drug effects,metabolism Organ Size/physiology Ovariectomy Ovary/physiology Progestins/metabolism Rats Rats, Sprague-Dawley
Chemicals
Estrogen Receptor alpha Estrogen Receptor beta Estrogens Progestins Enkephalin, Leucine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Torres-Reveron Annelyn
Division of Neurobiology, Department of Neurology and Neuroscience, Weill Cornell Medical College, 411 East 69th Street, New York, NY 10021, USA. [email protected]
Khalid Sana
Williams Tanya J
Waters Elizabeth M
Drake Carrie T
McEwen Bruce S
Milner Teresa A
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Article Info
Journal
Brain research
Abbr.
Brain Res
ISSN
0006-8993
DOI
10.1016/j.brainres.2008.07.058
Email
[email protected]
Published
2008-09-26
Epub
2008-00-26
Pages
70-84
Language
English
Region
Netherlands
NLM ID
0045503
PMCID
PMC2639658
Subset
IM
Grants
NIDA NIH HHS · DA08259 · United States
NINDS NIH HHS · R01 NS007080 · United States
NIDA NIH HHS · R01 DA008259-12 · United States
NIDA NIH HHS · R01 DA008259 · United States
NIDA NIH HHS · R01 DA008259-13 · United States
NIDA NIH HHS · R01 DA008259-12S1 · United States
NINDS NIH HHS · R01 NS007080-41 · United States
NIDA NIH HHS · R01 DA008259-15 · United States
NIDA NIH HHS · R01 DA008259-14 · United States
NINDS NIH HHS · NS07080 · United States
NIDA NIH HHS · R01 DA008259-11A2 · United States
NIGMS NIH HHS · T32 GM007739 · United States
External Links
PubMed source DOI: 10.1016/j.brainres.2008.07.058 PMC Full Text View journal details
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