AI Article Synopsis
- The decrease in estrogen levels during menopause is linked to depression, likely due to estrogens' effects in the brain, particularly through interactions with the serotonin system.
- Researchers tested whether the hormone 17beta-estradiol (E2) could have antidepressant effects in female mice that had their ovaries removed, focusing on the role of estrogen receptor beta (ER-beta).
- The study found that E2 reduced depressive behavior in mice and required multiple doses to be effective, with the effect not observed in mice lacking ER-beta, suggesting that targeting ER-beta could be a potential method to address mood disorders in postmenopausal women.
Article Abstract
Rationale: The decrease in levels of estrogens (ER) that occurs in menopause has been correlated with depressive disorders, probably due to ER direct and/or indirect effects in the brain, where these hormones act through both genomic (i.e. interaction as transcription factors with nuclear receptors ER-alpha and ER-beta) and non-genomic (i.e. binding with cell-membrane receptors) mechanisms. With respect to mood related disorders the interaction between ER-beta and the serotonin (5-HT) system is highly relevant. 17beta-Estradiol (E2) induces expression of the enzyme implicated in 5-HT synthesis - tryptophan hydroxylase (TPH), and this effect is mediated through ER-beta located in 5-HT cell bodies of the dorsal raphe nucleus (DRN).
Objective: The present studies tested the hypothesis that E2 induces antidepressant-like effects in female ovariectomized (OVX) mice, and that expression of ER-beta is mandatory for such effects.
Methods: The Forced Swim Test (FST) was used in three experiments to assess (a) dose response effect of E2 in outbred and inbred mouse strains, (b) length of treatment necessary for effect, (c) and role of ER-beta receptors.
Results: E2 (100 or 200 microg/kg), as well as the antidepressant desipramine (DMI), significantly reduced total duration of immobility in the FST in mice from different strains. Four consecutive daily doses (200 microg/kg) were required for such effect, which was absent in mice lacking the gene coding for ER-beta (BERKO mice).
Conclusion: These data suggest that E2-induced antidepressant-like effects in mice are mediated through activation of ER-beta. They offer preliminary support to the hypothesis that specific compounds acting at ER-beta may influence mood in postmenopausal women.
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| http://dx.doi.org/10.1007/s00213-004-2078-1 | DOI Listing |
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