Open Access

Downregulation of G‑protein‑coupled receptor 30 in the hippocampus attenuates the neuroprotection of estrogen in the critical period hypothesis

  • Authors:
    • Yingxi Wu
    • Dayun Feng
    • Jiaji Lin
    • Yan Qu
    • Shiming He
    • Yuan Wang
    • Guodong Gao
    • Tianzhi Zhao
  • View Affiliations

  • Published online on: February 16, 2018     https://doi.org/10.3892/mmr.2018.8618
  • Pages: 5716-5725
  • Copyright: © Wu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The aim of the present study was to investigate the role of G‑protein‑coupled receptor 30 (GPR30) in long‑term 17β‑estradiol (E2) deprivation (LTED) in a rat model with global cerebral ischemia (GCI), and its therapeutic target for ischemic stroke in the clinical setting. Following bilateral ovariectomy, GCI was induced in rats 1 or 10 weeks post‑surgery. To determine the protein and mRNA expression levels of GPR30 in the hippocampal CA1 region of LTED rats, short‑term E2 deprivation (STED) rats and naturally aging rats, western blot analysis and reverse transcription-quantitative polymerase chain reaction were performed. The results of the present study demonstrated that E2 treatment revealed significant neuroprotection post‑GCI in STED rats, but not in LTED rats, as well as a decrease in the expression levels of GPR30 in the hippocampal CA1 region. In LTED rats,. Notably, no effects were observed on the ubiquitination of GPR30 following investigation in STED or LTED rats. While the protein and mRNA expression levels of GPR30 were also decreased in the hippocampal CA1 region of female 24‑month‑old rats compared with 3‑month‑old rats. E2 treatment initiated for the entire ovariectomy period elevated GPR30 mRNA and protein expression levels, and attenuated the loss of hippocampal neurons in the GCI‑induced CA1 region, indicating that E2 treatment exerted robust neuroprotection within LTED rats. However, the neuroprotective effect of E2 may be blocked by G15. The results of the present study revealed that downregulation of GPR30 expression may attenuate the neuroprotection of E2 within LTED conditions in rats post‑ovariectomy by leading to neuronal insensitivity to E2 neuroprotection following cerebral ischemia. These results provide evidence that GPR30 may have potential as a novel therapeutic target for the treatment of clinical ischemic stroke.
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April-2018
Volume 17 Issue 4

Print ISSN: 1791-2997
Online ISSN:1791-3004

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Spandidos Publications style
Wu Y, Feng D, Lin J, Qu Y, He S, Wang Y, Gao G and Zhao T: Downregulation of G‑protein‑coupled receptor 30 in the hippocampus attenuates the neuroprotection of estrogen in the critical period hypothesis. Mol Med Rep 17: 5716-5725, 2018
APA
Wu, Y., Feng, D., Lin, J., Qu, Y., He, S., Wang, Y. ... Zhao, T. (2018). Downregulation of G‑protein‑coupled receptor 30 in the hippocampus attenuates the neuroprotection of estrogen in the critical period hypothesis. Molecular Medicine Reports, 17, 5716-5725. https://doi.org/10.3892/mmr.2018.8618
MLA
Wu, Y., Feng, D., Lin, J., Qu, Y., He, S., Wang, Y., Gao, G., Zhao, T."Downregulation of G‑protein‑coupled receptor 30 in the hippocampus attenuates the neuroprotection of estrogen in the critical period hypothesis". Molecular Medicine Reports 17.4 (2018): 5716-5725.
Chicago
Wu, Y., Feng, D., Lin, J., Qu, Y., He, S., Wang, Y., Gao, G., Zhao, T."Downregulation of G‑protein‑coupled receptor 30 in the hippocampus attenuates the neuroprotection of estrogen in the critical period hypothesis". Molecular Medicine Reports 17, no. 4 (2018): 5716-5725. https://doi.org/10.3892/mmr.2018.8618