Sex-specific Regulation of Spine Density and Synaptic Proteins by G-protein-coupled Estrogen Receptor (GPER)1 in Developing Hippocampus

被引:7
作者
Li, Xiaoyu [1 ]
Rune, Sonja Johann Gabriele M. [1 ]
Bender, Roland A. [1 ]
机构
[1] Univ Med Ctr Hamburg, Inst Neuroanat, Martinistr 52, D-20246 Hamburg, Germany
关键词
estrogen; development; synaptic plasticity; PSD95; cofilin; sex-specific; LONG-TERM POTENTIATION; DENDRITIC SPINES; MESSENGER-RNA; PLASTICITY; CA1; EXPRESSION; ESTRADIOL; FEMALE; GPR30; BRAIN;
D O I
10.1016/j.neuroscience.2021.07.035
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
1 (GPER1) is a membrane-bound receptor that mediates estrogen signaling via intracellular signaling cascades. We recently showed that GPER1 promotes the distal dendritic enrichment of hyperpolarization activated and cyclic nucleotide-gated (HCN)1 channels in CA1 stratum lacunosum-moleculare (SLM), suggesting a role of GPER1-mediated signaling in neuronal plasticity. Here we studied whether this role involves processes of structural plasticity, such as the regulation of spine and synapse density in SLM. In organotypic entorhino-hippocampal cultures from mice expressing eGFP, we analyzed spine densities in SLM after treatment with GPER1 agonist G1 (20 nM). G1 significantly increased the density of "non-stubby" spines (maturing spines with a spine head and a neck), but did so only in cultures from female mice. In support of this finding, the expression of synaptic proteins was sex-specifically altered in the cultures: G1 increased the protein (but not mRNA) expression of PSD95 and reduced the p-/n-cofilin ratio only in cultures from females. Application of E2 (2 nM) reproduced the sex-specific effect on spine density in SLM, but only partially on the expression of synaptic proteins. Spine synapse density was, however, not altered after G1-treatment, suggesting that the increased spine density did not translate into an increased spine synapse density in the culture model. Taken together, our results support a role of GPER1 in mediating structural plasticity in CA1 SLM, but suggest that in developing hippocampus, this role is sex-specific. (c) 2021 IBRO. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:35 / 50
页数:16
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