Original Article

Translational Stroke Research

, Volume 3, Issue 4, pp 500-507

First online:

GPER1/GPR30 Activation Improves Neuronal Survival Following Global Cerebral Ischemia Induced by Cardiac Arrest in Mice

  • Y. KosakaAffiliated withDepartment of Anesthesiology and Perioperative Medicine, Oregon Health and Science University
  • , N. QuillinanAffiliated withDepartment of Anesthesiology and Perioperative Medicine, Oregon Health and Science UniversityDepartment of Anesthesiology, University of Colorado Denver
  • , C. T. BondAffiliated withVollum Institute, Oregon Health and Science University
  • , R. J. TraystmanAffiliated withDepartment of Anesthesiology, University of Colorado DenverDepartment of Pharmacology, University of Colorado Denver
  • , P. D. HurnAffiliated withDepartment of Neurobiology, University of Texas at Austin
  • , P. S. HersonAffiliated withDepartment of Anesthesiology and Perioperative Medicine, Oregon Health and Science UniversityDepartment of Anesthesiology, University of Colorado Denver Email author 

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Abstract

Female sex steroids, particularly estrogens, contribute to the sexually dimorphic response observed in cerebral ischemic outcome, with females being relatively protected compared to males. Using a mouse model of cardiac arrest and cardiopulmonary resuscitation, we previously demonstrated that estrogen neuroprotection is mediated in part by the estrogen receptor β, with no involvement of estrogen receptor α. In this study, we examined the neuroprotective effect of the novel estrogen receptor, G protein-coupled estrogen receptor 1 (GPER1/GPR30). Male mice administered with the GPR30 agonist G1 exhibited significantly reduced neuronal injury in the hippocampal CA1 region and striatum. The magnitude of neuroprotection observed in G1-treated mice was indistinguishable from estrogen-treated mice, implicating GPR30 in estrogen neuroprotection. Real-time quantitative RT-PCR indicates that G1 treatment increases expression of the neuroprotective ion channel, small-conductance calcium-activated potassium channel 2. We conclude that GPR30 agonists show promise in reducing brain injury following global cerebral ischemia.

Keywords

Cardiac arrest GPR30/GPER1 SK2 Cerebral ischemia G1