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 to rats in proestrus or diestrus. OVX rats exposed to estradiol for 24 hrs showed increased DYN-ir in the DG and CA3, while those with 72 hrs estradiol exposure showed increases only in the DG. Six hrs 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.

G-Protein-Coupled Estrogen Receptor 1 Is Anatomically Positioned to Modulate Synaptic Plasticity in the Mouse Hippocampus

“…tified previously with markers exclusively found in axons and terminals (i.e., tyrosine hydroxylase and enkephalin; Milner and Bacon, 1989;Torres-Reveron et al, 2008). In particular, unmyelinated axons did not conform to the boundaries of the neuropil as glial processes do.…”

“…Data for each profile type are presented in Table 3 as a total number of profiles per group. Third, a lamina analysis limited to the CA1 stratum radiatum (distal) and the CA3 stratum lucidum was performed because of their known sensitivity to estrogens (McEwen and Milner, 2007;Torres-Reveron et al, 2008 and because ERs, progestin receptors, and phosphorylated TrkB-labeled axons fluctuate across the estrous cycle in these regions in the same mice used for the present studies (Mitterling et al, 2010;Spencer-Segal et al, 2011). For this, profile type and group were compared by one-way ANOVA followed by a Tukey-Kramer post hoc test.…”

Ovarian hormones modify anxiety behavior and glucocorticoid receptors after chronic social isolation stress

“…The estrous cycle phase of female rats was determined for 8 consecutive days at the beginning of the housing period and during 10 consecutive days prior to behavioral testing using vaginal smear cytology [28–30]. Length of estrous cycle and cyclicity was determined by the frequency of proestrus presentations within the time measured.…”

Stress and opioids: Role of opioids in modulating stress-related behavior and effect of stress on morphine conditioned place preference

“…females (Torres-Reveron et al, 2008) and dynorphin immunoreactivity in the hippocampus (Torres-Reveron et al, 2009). The mossy fiber-CA3 pathway is the most stress vulnerable region in males, and is rich in opioid peptides and receptors as well as gonadal steroid receptors (Drake et al, 2007a,b).…”