Roles of estrogen receptors alpha and beta in sexually dimorphic neuroprotection against glutamate toxicity

D. N. Bryant, D. M. Dorsa

Research output: Contribution to journalArticlepeer-review

38 Scopus citations


Although most agree that 17β-estradiol is neuroprotective via a variety of mechanisms, less is known about the role that biological sex plays in receptor-mediated estradiol neuroprotection. To address this issue we isolated primary cortical neurons from rat pups sorted by sex and assessed the ability of estradiol to protect the neurons from death induced by glutamate. Five-minute pretreatment with 10-50 nM 17β-estradiol protected female but not male neurons from glutamate toxicity 24 h later. Both estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) are expressed in these cultures. Experiments using an ERα selective agonist or antagonist indicate that this receptor is important for neuroprotection in female cortical neurons. The ERβ selective agonist conveys a small degree of neuroprotection to both male and female cortical neurons. Interestingly, we found that 17α estradiol and the novel membrane estrogen receptor (mER) agonist STX, but not bovine serum albumin conjugated estradiol or the GPR30 agonist G1 were neuroprotective in both male and female neurons. Taken together these data highlight a role for ERα in sexually dimorphic neuroprotection.

Original languageEnglish (US)
Pages (from-to)1261-1269
Number of pages9
Issue number4
StatePublished - Nov 2010

Bibliographical note

Funding Information:
We would like to acknowledge Drs. Robert Shapiro and Laird Sheldahl for helpful suggestions and discussions as well as Drs. Tom Scanlan and Martin Kelly for kindly providing the STX. This work was supported by NIH NS 20311 (DMD) and BIRCWH NIH K12HD043488 .


  • Estrogen receptor alpha
  • Estrogen receptor beta
  • Glutamate
  • Neuroprotection
  • Primary cortical neuron
  • Sexually dimorphic

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