title: G-protein coupled estrogen receptor 1 mediated estrogenic neuroprotection against spinal cord injury.
abstract: 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.
  
  
  METHODS
  Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  The animals subjected to spinal cord injury were divided into six groups and given vehicle solution, 17β-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 17β-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 17β-estradiol administration at 15 mins and 24 hrs postinjury.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Department of Neurosurgery and Key Laboratory of Neurotrauma, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Haodong
authors.initials: H
authors.lastname: Sun
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Jingyu
authors.initials: J
authors.lastname: Chen
authors.forename: Nan
authors.initials: N
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Meng
authors.forename: Gaoyu
authors.initials: G
authors.lastname: Cui
authors.forename: Shengli
authors.initials: S
authors.lastname: Hu
authors.forename: Fei
authors.initials: F
authors.lastname: Li
authors.forename: Jiangkai
authors.initials: J
authors.lastname: Lin
authors.forename: Qi
authors.initials: Q
authors.lastname: Wan
authors.forename: Hua
authors.initials: H
authors.lastname: Feng
mesh_terms: D000818:Animals; D003517:Cyclopentanes / Q000627:therapeutic use; D004958:Estradiol / Q000031:analogs & derivatives / Q000627:therapeutic use; D004965:Estrogen Antagonists / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000819:agonists* / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000077267:Fulvestrant; D007150:Immunohistochemistry; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013119:Spinal Cord Injuries / Q000188:drug therapy*
chemical_list: C517943:1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone; D003517:Cyclopentanes; D004965:Estrogen Antagonists; D047628:Estrogen Receptor alpha; D018696:Neuroprotective Agents; D011804:Quinolines; D043562:Receptors, G-Protein-Coupled; D000077267:Fulvestrant; D004958:Estradiol