Sex and estrogen receptor expression influence opioid peptide levels in the mouse hippocampal mossy fiber pathway.
The opioid peptides, dynorphin (DYN) and enkephalin (L-ENK) are contained in the hippocampal mossy fiber pathway where they modulate synaptic plasticity. In rats, the levels of DYN and L-ENK immunoreactivity (-ir) are increased when estrogen levels are elevated (Torres-Reveron et al., 2008, 2009). Here, we used quantitative immunocytochemistry to examine whether opioid levels are similarly regulated in wildtype (WT) mice over the estrous cycle, and how these compared to males. Moreover, using estrogen receptor (ER) alpha and beta knock-out mice (AERKO and BERKO, respectively), the present study examined the role of ERs in rapid, membrane-initiated (6 h), or slower, nucleus-initiated (48 h) estradiol effects on mossy fiber opioid levels. Unlike rats, the levels of DYN and L-ENK-ir did not change over the estrous cycle. However, compared to males, females had higher levels of DYN-ir in CA3a and L-ENK-ir in CA3b. In WT and BERKO ovariectomized (OVX) mice, neither DYN- nor L-ENK-ir changed following 6 or 48 h estradiol benzoate (EB) administration. However, DYN-ir significantly increased 48 h after EB in the dentate gyrus (DG) and CA3b of AERKO mice only. These findings suggest that cyclic hormone levels regulate neither DYN nor L-ENK levels in the mouse mossy fiber pathway as they do in the rat. This may be due to species-specific differences in the mossy fiber pathway. However, in the mouse, DYN levels are regulated by exogenous EB in the absence of ERα possibly via an ERβ-mediated pathway requiring new gene transcription.
Brain and Mind Research Institute, Weill Cornell Medical College, 407 East 61st Street, New York, NY 10065, United States. Electronic address: tav2002@med.cornell.edu.
Tracey A
TA
Van Kempen
Sana
S
Kahlid
Andreina D
AD
Gonzalez
Joanna L
JL
Spencer-Segal
Mumeko C
MC
Tsuda
Sonoko
S
Ogawa
Bruce S
BS
McEwen
Elizabeth M
EM
Waters
Teresa A
TA
Milner
D000818:Animals; D056654:CA3 Region, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D018891:Dentate Gyrus / Q000187:drug effects / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000502:physiology*; D047629:Estrogen Receptor beta / Q000235:genetics / Q000502:physiology*; D030762:Estrous Cycle / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019599:Mossy Fibers, Hippocampal / Q000187:drug effects / Q000378:metabolism*; D012727:Sex Characteristics
D004745:Enkephalins; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; C074283:estradiol 3-benzoate; D004958:Estradiol; D004399:Dynorphins
AERKO; BDNF; BERKO; BSA; CA1; CA3; CA3 region; DG; DYN; Dentate gyrus; EB; ER; G-protein-coupled estrogen receptor 1; GPER1; Hil; IgG; L-ENK; LTP; OVX; Opioids; PB; Synaptic plasticity; TS; WT; bovine serum albumin; brain derived neurotrophic factor; cornu ammonis 1 region; cornu ammonis 3 region; dentate gyrus; dynorphin; estradiol benzoate; estrogen receptor; estrogen receptor alpha knock out mice; estrogen receptor beta knock out mice; glc; granule cell layer; hilus of the dentate gyrus; immunoglobulin; immunoreactivity; ir; leu-enkephalin; long term potentiation; ovariectomy; pcl; phosphate buffer; pyramidal cell layer; slu; sr; stratum lucidum; stratum radiatum; tris–saline; wild-type mice