Abstract

Estradiol increases cell proliferation in the dentate gyrus of the female rodent but it is not known whether the G protein-coupled estrogen receptor (GPER), a membrane receptor, is involved in this process, nor whether there are regional differences in estradiol’s effects on cell proliferation. Thus, we investigated whether estradiol exerts its effects on cell proliferation in the dorsal and ventral dentate gyrus through GPER, using the GPER agonist, G1, and antagonist, G15. Ovariectomized adult female rats received a single injection of either: 17β-estradiol (10 μg), G1 (0.1, 5, 10 μg), G15 (40 μg), G15 and estradiol, or vehicle (oil, DMSO, or oil+DMSO). After 30 min, animals received an injection of bromodeoxyuridine (BrdU) and were perfused 24 h later. Acute treatment with estradiol increased, while the GPER agonist G1 (5 μg) decreased, the number of BrdU+ cells in the dentate gyrus relative to controls. The GPER antagonist, G15 increased the number of BrdU+ cells relative to control in the dorsal region and decreased the number of BrdU+ cells in the ventral region. However, G15 treatment in conjunction with estradiol partially eliminated the estradiol-induced increase in cell proliferation in the dorsal dentate gyrus. Furthermore, G1 decreased the expression of GPER in the dentate gyrus but not the CA1 and CA3 regions of the hippocampus. In summary, we found that activation of GPER decreased cell proliferation and GPER expression in the dentate gyrus of young female rats, presenting a potential and novel estrogen-independent role for this receptor in the adult hippocampus.

Highlights

  • Neurogenesis occurs throughout the lifespan in the mammalian dentate gyrus [1,2,3,4]

  • Hilus volume was significantly larger than the granule cell layer (GCL) (Region effect: Experiment 1 F(1,19) = 716.65; P

  • Activation of G protein-coupled estrogen receptor (GPER) decreased cell proliferation in the dorsal hippocampus, while inactivation of GPER increased or decreased cell proliferation depending on the region of the dentate gyrus in female rats

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Summary

Introduction

Neurogenesis occurs throughout the lifespan in the mammalian dentate gyrus [1,2,3,4]. Estradiol influences hippocampal neurogenesis by modulating both cell proliferation and survival of young neurons in female rodents (reviewed in [5]). In ovariectomized young adult female rats, 17β-estradiol increases cell proliferation after 30 minutes and 2 hours of exposure, but not after 4 hours [6,7,8] and decreases cell proliferation after 48 h [9]. PLOS ONE | DOI:10.1371/journal.pone.0129880 June 15, 2015

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