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Ovarian Cycle‐Related Neurosteroid Regulation of GABA‐A Receptor Subunit Plasticity in the Hippocampus Subfields
Author(s) -
Gangisetty Omkaram,
Reddy Doodipala Samba
Publication year - 2011
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.25.1_supplement.lb410
Subject(s) - neuroactive steroid , endocrinology , medicine , estrous cycle , allopregnanolone , gabaa receptor , dentate gyrus , protein subunit , biology , luteal phase , downregulation and upregulation , receptor , hippocampus , chemistry , hormone , biochemistry , gene
Progesterone (P) plays a key role in epilepsy via modulation of GABA‐A receptors in the brain. Seizures decrease in the mid‐luteal phase (high P) and increase during the perimenstrual period (low P) in women with epilepsy. However, the mechanisms underlying the menstrual cycle‐differences in seizure susceptibility are not clear. Here we tested the hypothesis that ovarian alterations in GABA‐A receptor plasticity contributes to seizure susceptibility. The TaqMan assay was used for quantification of GABA‐A (α1‐4, β2, γ2,δ) subunit mRNAs in the CA1, CA3 and dentate gyrus (DG) at different estrous cycle stages. The δ‐subunit was strikingly (4‐folds) increased during the diestrous stage than the estrous stage in the DG region. No such change was noted in the CA1 or CA3 regions. There was a marked increase in α1 and α2 subunits in the DG during diestrous stage. In contrast, no changes in levels of γ2 subunit expression were observed during the diestrous stage. The level of δ‐subunit was not affected by ovariectomy suggesting the role of ovarian cycle. The diestrous upregulation of δ‐subunit was undiminished in PR knockout mice, but it was significantly reduced in mice treated with finasteride, a neurosteroid synthesis inhibitor. These results suggest that GABA‐A δ subunit expression is regulated by ovarian P‐derived neurosteroids that control tonic inhibition and catamenial epilepsy. ** Supported by NIH grant NS051398 **