Ovarian cycle-linked changes in GABA(A) receptors mediating tonic inhibition alter seizure susceptibility and anxiety
- PMID: 15895085
- DOI: 10.1038/nn1469
Ovarian cycle-linked changes in GABA(A) receptors mediating tonic inhibition alter seizure susceptibility and anxiety
Abstract
Disturbances of neuronal excitability changes during the ovarian cycle may elevate seizure frequency in women with catamenial epilepsy and enhance anxiety in premenstrual dysphoric disorder (PMDD). The mechanisms underlying these changes are unknown, but they could result from the effects of fluctuations in progesterone-derived neurosteroids on the brain. Neurosteroids and some anxiolytics share an important site of action: tonic inhibition mediated by delta subunit-containing GABA(A) receptors (deltaGABA(A)Rs). Here we demonstrate periodic alterations in specific GABA(A)R subunits during the estrous cycle in mice, causing cyclic changes of tonic inhibition in hippocampal neurons. In late diestrus (high-progesterone phase), enhanced expression of deltaGABA(A)Rs increases tonic inhibition, and a reduced neuronal excitability is reflected by diminished seizure susceptibility and anxiety. Eliminating cycling of deltaGABA(A)Rs by antisense RNA treatment or gene knockout prevents the lowering of excitability during diestrus. Our findings are consistent with possible deficiencies in regulatory mechanisms controlling normal cycling of deltaGABA(A)Rs in individuals with catamenial epilepsy or PMDD.
Comment in
-
A woman's prerogative.Nat Neurosci. 2005 Jun;8(6):697-9. doi: 10.1038/nn0605-697. Nat Neurosci. 2005. PMID: 15917829 No abstract available.
-
Dancing the delta shuffle: neurosteroids regulate GABAA receptor expression.Epilepsy Curr. 2006 Jan-Feb;6(1):14-7. doi: 10.1111/j.1535-7511.2005.00081.x. Epilepsy Curr. 2006. PMID: 16477317 Free PMC article. No abstract available.
Similar articles
-
A woman's prerogative.Nat Neurosci. 2005 Jun;8(6):697-9. doi: 10.1038/nn0605-697. Nat Neurosci. 2005. PMID: 15917829 No abstract available.
-
Gonadal steroids regulate GABAA receptor subunit mRNA expression in NT2-N neurons.Brain Res Mol Brain Res. 2005 Aug 18;138(2):105-15. doi: 10.1016/j.molbrainres.2004.10.047. Brain Res Mol Brain Res. 2005. PMID: 16000229
-
Estrous cycle regulation of extrasynaptic δ-containing GABA(A) receptor-mediated tonic inhibition and limbic epileptogenesis.J Pharmacol Exp Ther. 2013 Jul;346(1):146-60. doi: 10.1124/jpet.113.203653. Epub 2013 May 10. J Pharmacol Exp Ther. 2013. PMID: 23667248 Free PMC article.
-
Plasticity of GABAA receptor subunit expression during the oestrous cycle of the rat: implications for premenstrual syndrome in women.Exp Physiol. 2006 Jul;91(4):655-60. doi: 10.1113/expphysiol.2005.032342. Epub 2006 Jun 1. Exp Physiol. 2006. PMID: 16740643 Review.
-
Role of neurosteroids in catamenial epilepsy.Epilepsy Res. 2004 Dec;62(2-3):99-118. doi: 10.1016/j.eplepsyres.2004.09.003. Epilepsy Res. 2004. PMID: 15579299 Review.
Cited by
-
Parvalbumin interneuron mGlu5 receptors govern sex differences in prefrontal cortex physiology and binge drinking.Neuropsychopharmacology. 2024 May 21. doi: 10.1038/s41386-024-01889-0. Online ahead of print. Neuropsychopharmacology. 2024. PMID: 38773314
-
GABA system as the cause and effect in early development.Neurosci Biobehav Rev. 2024 Jun;161:105651. doi: 10.1016/j.neubiorev.2024.105651. Epub 2024 Apr 4. Neurosci Biobehav Rev. 2024. PMID: 38579901 Review.
-
Impaired extinction of cocaine seeking in HIV-infected mice is accompanied by peripheral and central immune dysregulation.Commun Biol. 2024 Mar 30;7(1):387. doi: 10.1038/s42003-024-06079-8. Commun Biol. 2024. PMID: 38553542 Free PMC article.
-
The impact of stress on the behavior of C57BL/6 mice with liver injury: a comparative study.Front Behav Neurosci. 2024 Mar 6;18:1358964. doi: 10.3389/fnbeh.2024.1358964. eCollection 2024. Front Behav Neurosci. 2024. PMID: 38510829 Free PMC article.
-
Early IGF-1 receptor inhibition in mice mimics preterm human brain disorders and reveals a therapeutic target.Sci Adv. 2024 Mar;10(9):eadk8123. doi: 10.1126/sciadv.adk8123. Epub 2024 Mar 1. Sci Adv. 2024. PMID: 38427732 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases