GABAAR Plasticity during Pregnancy: Relevance to Postpartum Depression
Open accessAbstract
Fluctuating neurosteroid levels over the ovarian cycle modulate neuronal excitability through effects on GABA(A) receptors (GABA(A)Rs). The large increase in progesterone-derived neurosteroids during pregnancy and their precipitous decline at parturition may have considerable effects on GABA(A)Rs during pregnancy and postpartum. Here we show a significant decrease in tonic and phasic inhibitions in pregnant mice, mediated by a downregulation of GABA(A)R delta and gamma2 subunits, respectively, which rebounds immediately postpartum. Mice which do not exhibit GABA(A)R delta subunit regulation throughout pregnancy (Gabrd(+/-) and Gabrd(-/-)) exhibit depression-like and abnormal maternal behaviors, resulting in reduced pup survival. These abnormal postpartum behaviors were ameliorated in Gabrd(+/-) mice by a GABA(A)R delta-subunit-selective agonist, THIP. We suggest that Gabrd(+/-) and Gabrd(-/-) mice constitute a mouse model of postpartum depression that may be useful for evaluating potential therapeutic interventions.
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Animal model studies demonstrate postpartum depression-like behaviors in mice lacking the extrasynaptic GABAAR δ subunit or KCC2, and functionally link GABA with the hypothalamic-pituitary axis.
“The role of GABAergic signaling is further supported by animal model studies demonstrating PPD-like behaviors in mice lacking the extrasynaptic GABAAR δ subunit or potassium/chloride cotransporter KCC2, and these PPD models also functionally link GABA with the hypothalamic-pituitary axis, a stress pathway implicated in PPD.34,35”
From Effect of Zuranolone vs Placebo in Postpartum Depression (2021) · cites this paper as [34]
The Results and Discussion report postpartum depression-like behavior in mice deficient in the GABAAR δ subunit. The passages do not report a KCC2-deficient mouse model or a functional link between GABA and the hypothalamic-pituitary axis; searches for KCC2 and that axis found no supporting passage in our copy. Page numbers were not available. (LLM, conf=0.87)
Experimental — accuracy not yet measuredExpression of the δ subunit itself can be altered in part due to changes in the levels of circulating neurosteroids that occur during stress, puberty, menstrual cycle, and pregnancy.
“Interestingly, expression of the δ subunit itself can be altered in part due to changes in the levels of circulating neurosteroids that occur during stress, puberty, menstrual cycle, and pregnancy (726, 732, 733, 807).”
From Hippocampal GABAergic Inhibitory Interneurons (2017) · cites this paper as [732]
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- Authors
- Maguire, J., & Mody, I.
- Affiliations
- University of California, Los Angeles (US)
- ORCID
- Maguire, Jamie
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 59
- Issue
- 2
- Pages
- 207-213
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC2875248
- OpenAlex
- W1994775090
- Cited by
- 437
- References
- 35
- Citations by year
- 2026: 20 · 2025: 29 · 2024: 32 · 2023: 29 · 2022: 25 · 2021: 23 · 2020: 38 · 2019: 33 · 2018: 17 · 2017: 18 · 2016: 19 · 2015: 23 · 2014: 27 · 2013: 20 · 2012: 21
- FWCI
- 20.77
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1878 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Universität Wien
- Tehran University of Medical Sciences and Health Services
- National Institutes of Health
- National Institute of Mental Health (MH076994, R01MH076994)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- GABAA receptor, GABA-A receptor gamma2 subunit, pregnancy, postpartum depression, neurosteroids, progesterone, neuronal inhibition, THIP, maternal behavior, pup survival, mouse model of depression
- MeSH terms
- Animals, Female, Maternal Behavior, Mice, Inbred C57BL, Pregnancy, Pregnancy Complications, Receptors, GABA-A, Down-Regulation, Mice, Knockout, Depression, Postpartum, Mice, GABA-A Receptor Antagonists
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