G‑protein‑coupled receptor 30‑mediated antiapoptotic effect of estrogen on spinal motor neurons following injury and its underlying mechanisms

Chen,Jingyu; Hu,Rong; Ge,Hongfei; Duanmu,Wangsheng; Li,Yuhong; Xue,Xingseng; Hu,Shengli; Feng,Hua

doi:10.3892/mmr.2015.3601

G‑protein‑coupled receptor 30‑mediated antiapoptotic effect of estrogen on spinal motor neurons following injury and its underlying mechanisms

Authors:
- Jingyu Chen
- Rong Hu
- Hongfei Ge
- Wangsheng Duanmu
- Yuhong Li
- Xingseng Xue
- Shengli Hu
- Hua Feng
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Affiliations: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
Published online on: April 8, 2015 https://doi.org/10.3892/mmr.2015.3601
Pages: 1733-1740
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Spinal cord injury (SCI) may result in severe dysfunction of motor neurons. G‑protein‑coupled receptor 30 (GPR30) expression in the motor neurons of the ventral horn of the spinal cord mediates neuroprotection through estrogen signaling. The present study explored the antiapoptotic effect of estrogen, mediated by GPR30 following SCI, and the mechanisms underlying this effect. Spinal motor neurons from rats were cultured in vitro in order to establish cell models of oxygen and glucose deprivation (OGD). The effects of estrogen, the estrogen agonist, G1, and the estrogen inhibitor, G15, on motor neurons were observed using MTT assays. The effects of E2, G1 and G15 on spinal motor neuron apoptosis following OGD, were detected using flow cytometry. The role of the phosphatidylinositol 3‑kinase/protein kinase B (PI3K/Akt) inhibitor, LY294002, was also determined using flow cytometry. Rat SCI models were established. E2, G1 and E2+LY294002 were administered in vivo. Motor function was scored at 3, 7, 14, 21 and 28 d following injury, using Basso‑Beattie‑Bresnahan (BBB) standards. Cell activity in the estrogen and G1 groups was higher than that in the solvent group, whereas cell activity in the E2+G15 group was lower than that in the E2 group (P<0.05). Following OGD, the proportion of apoptotic cells significantly increased (P<0.05). The proportion in the estrogen group was significantly lower than that in the solvent group, whereas the proportion of apoptotic cells in the E2+G15 and E2+LY294002 groups was higher than that in the E2 group (P<0.05). Treatment with E2 and G1 led to upregulation of P‑Akt expression in normal cells and post‑OGD cells. The BBB scores of rats in the E2 and G1 groups were higher than those in the placebo group (P<0.05). The BBB scores of the E2+LY294002 group were lower than those of the E2 group (P<0.05). Estrogen thus appears to exert a protective effect on spinal motor neurons following OGD, via GPR30. The PI3K/Akt pathway may be one of those involved in the estrogen‑related antiapoptotic effects mediated by GPR30.

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