RGD Reference Report - G-protein coupled estrogen receptor 1 mediated estrogenic neuroprotection against spinal cord injury. - Rat Genome Database

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G-protein coupled estrogen receptor 1 mediated estrogenic neuroprotection against spinal cord injury.

Authors: Hu, R  Sun, H  Zhang, Q  Chen, J  Wu, N  Meng, H  Cui, G  Hu, S  Li, F  Lin, J  Wan, Q  Feng, H 
Citation: Hu R, etal., Crit Care Med. 2012 Dec;40(12):3230-7. doi: 10.1097/CCM.0b013e3182657560.
RGD ID: 8552988
Pubmed: PMID:22975889   (View Abstract at PubMed)
DOI: DOI:10.1097/CCM.0b013e3182657560   (Journal Full-text)

OBJECTIVE: What underlies the protection of estrogen against spinal cord injury remains largely unclear. Here, we investigated the expression pattern of a new estrogen receptor, G-protein coupled estrogen receptor 1 in the spinal cord and its role in estrogenic protection against spinal cord injury. DESIGN AND SETTINGS: Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital. SUBJECTS: Male Sprague-Dawley rats. INTERVENTIONS: The animals subjected to spinal cord injury were divided into six groups and given vehicle solution, 17beta-estradiol, or G-protein coupled estrogen receptor 1 agonist G-1 at 15 mins and 24 hrs postinjury, or given nuclear estrogen receptor antagonist ICI 182,780 at 1 hr before spinal cord injury followed by 17beta-estradiol administration at 15 mins and 24 hrs postinjury, or given G-protein coupled estrogen receptor 1 specific antisense or random control oligonucleotide at 4 days before spinal cord injury followed by 17beta-estradiol administration at 15 mins and 24 hrs postinjury. MEASUREMENTS: Male Sprague-Dawley rats were subjected to spinal cord injury using a weight-drop injury approach. Immunohistochemical assays were used to observe the distribution and cell-type expression pattern of G-protein coupled estrogen receptor 1. The terminal deoxynucleotidyl transferase dUTP nick-end labeling-staining assay and behavior tests were employed to assess the role of G-protein coupled estrogen receptor 1 in mediating estrogenic protection against spinal cord injury. MAIN RESULTS: We show that G-protein coupled estrogen receptor 1 is mainly distributed in the ventral horn and white matter of the spinal cord, which is totally different from nuclear estrogen receptors. We also show that G-protein coupled estrogen receptor 1 is specifically expressed by neurons, oligodendrocytes, and microglial cells, but not astrocytes. Furthermore, estrogen treatment prevents spinal cord injury-induced apoptotic cell death and enhances functional recovery after spinal cord injury, which can be mimicked by the specific G-protein coupled estrogen receptor 1 agonist G-1 and inhibited by specific knockdown of G-protein coupled estrogen receptor 1 expression, but not pure nuclear ER antagonist ICI 182,780. Finally, we show that estrogen or G-1 up-regulates the protein expression level of G-protein coupled estrogen receptor 1 to intensify estrogenic effects during spinal cord injury. CONCLUSIONS: These results reveal that G-protein coupled estrogen receptor 1 may mediate estrogenic neuroprotection against spinal cord injury, and underline the promising potential of estrogen with its new target G-protein coupled estrogen receptor 1 for the treatment of spinal cord injury patients.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Spinal Cord Injuries  ISOGper1 (Rattus norvegicus)8552988; 8552988 RGD 
Spinal Cord Injuries  IMP 8552988 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of apoptotic process  IMP 8552988 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gper1  (G protein-coupled estrogen receptor 1)

Genes (Mus musculus)
Gper1  (G protein-coupled estrogen receptor 1)

Genes (Homo sapiens)
GPER1  (G protein-coupled estrogen receptor 1)


Additional Information