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Mechanisms of Estrogen Receptor Neuroprotection in Dopamine Neurons
Author(s) -
Roberts James
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.231.1
Subject(s) - neuroprotection , dopamine , estrogen , dopaminergic , estrogen receptor , neuron , agonist , chemistry , estrogen receptor beta , pharmacology , endocrinology , medicine , neuroscience , biology , receptor , cancer , breast cancer
Estrogen involvement in neuroprotection is now a widely accepted research area, although the mechanisms of estrogen action in neuroprotection remain unclear. To investigate the neuroprotective effects of 17‐β estradiol on dopaminergic neurons we utilized primary mesencephalic neurons cultured from embryos of time‐mated C57 Bl/6 mice. The primary mesencephalic cultures allow for analysis of both direct estrogen‐mediated neuorprotection on the dopamine neuron and/or indirect actions through surrounding glial cells. We demonstrate the existence of both ERα and ERβ with a predominance of ERα on both dopamine neurons and astrocytes. In primary cultures of mouse mesencephalic neurons estrogen protects dopamine neurons from injury induced by 1‐methyl‐4‐phenyl pyridium (MPP+). ERα mediated the protection afforded by estrogen since only the ERα agonist HPTE protected against dopamine cell loss. The ERβ agonist DPN, alone did not protect against MPP+ induced neuronal death. Since glial cells were shown to express ERα we investigated an indirect mechanism of estrogen action on dopamine neuron survival. Treating the cultures with the mitotic inhibitor, 5‐Fluoro‐2’‐deoxyuridine (dFUR) abolished glial cells and significantly reduced the amount of neuroprotection seen with estrogen. These data indicate that neuroprotection provided by estrogen is mediated by ERα and involves a interplay among several cell types.