دورية أكاديمية
أعرض في EDS

Intrinsically dysregulated cellular stress signaling genes and gene networks in postpartum depression.

التفاصيل البيبلوغرافية
العنوان: Intrinsically dysregulated cellular stress signaling genes and gene networks in postpartum depression.
المؤلفون: Rudzinskas SA; Behavioral Endocrinology Branch, NIMH, Bldg. 10CRC, Room 25330, 10 Center Drive MSC 1277, Bethesda, 20892-1277, MD, USA.; Laboratory of Neurogenetics, NIAAA, Bethesda, MD, USA., Goff AC; Behavioral Endocrinology Branch, NIMH, Bldg. 10CRC, Room 25330, 10 Center Drive MSC 1277, Bethesda, 20892-1277, MD, USA.; Laboratory of Neurogenetics, NIAAA, Bethesda, MD, USA., Mazzu MA; Behavioral Endocrinology Branch, NIMH, Bldg. 10CRC, Room 25330, 10 Center Drive MSC 1277, Bethesda, 20892-1277, MD, USA.; Laboratory of Neurogenetics, NIAAA, Bethesda, MD, USA., Schiller CE; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA., Meltzer-Brody S; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA., Rubinow DR; Department of Psychiatry, University of North Carolina, Chapel Hill, NC, USA., Schmidt PJ; Behavioral Endocrinology Branch, NIMH, Bldg. 10CRC, Room 25330, 10 Center Drive MSC 1277, Bethesda, 20892-1277, MD, USA. peterschmidt@mail.nih.gov., Goldman D; Laboratory of Neurogenetics, NIAAA, Bethesda, MD, USA.
المصدر: Molecular psychiatry [Mol Psychiatry] 2023 Jul; Vol. 28 (7), pp. 3023-3032. Date of Electronic Publication: 2023 Feb 13.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-5578 (Electronic) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE
أسماء مطبوعة: Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals
Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996-
مواضيع طبية MeSH: Depression, Postpartum*/genetics , Depression, Postpartum*/metabolism, Pregnancy ; Female ; Humans ; Gene Regulatory Networks/genetics ; Estradiol ; Progesterone ; Estrogens
مستخلص: Postpartum depression (PPD) is a leading cause of morbidity and mortality among women. Clinically, the administration and withdrawal of supraphysiologic estradiol and progesterone (E2 + P) can cause affective symptom reoccurrence in women with a history of PPD, but not matched controls. To investigate the cellular basis underlying this differential affective response, lymphoblastoid cell lines (LCLs) were derived from women with and without past PPD and compared transcriptomically in hormone conditions mimicking pregnancy and parturition: supraphysiologic E2 + P-addback; supraphysiologic E2 + P-withdrawal; and no added E2 + P (Baseline). RNA-sequencing identified unique differentially expressed genes (DEGs) in all hormone conditions, but the majority tended to be downregulated in PPD and observed in E2 + P-addback. Two of these DEGs were evolutionarily conserved cellular stress regulators: IMPACT, an integrative response protein maintaining translational homeostasis, and WWTR1, a transcriptional coactivator in the 'Hippo' pathway mediating cell proliferation and survival. Correspondingly, significant gene network modules were linked to cell cycle progression, estrogen response, and immune dysregulation, suggesting innate differences in intracellular signaling in PPD. In certain hormone conditions, PPD LCLs displayed increased GATA3 expression (an upstream regulator of IMPACT and WWTR1) and differentially phosphorylated eiF2α (the ultimate downstream target of IMPACT). Taken together, these transcriptomic data primarily implicate innately dysregulated cellular responses as potentially influencing mood and/or escalating PPD risk. Furthermore, the intrinsic downregulation of IMPACT's translation and WWTR1's transcription networks may suggest a novel link between PPD and a compromised ability to maintain homeostasis in the context of cellular stress occurring during pregnancy and parturition.
(© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
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معلومات مُعتمدة: K24 AA000301 United States AA NIAAA NIH HHS; R21 MH101409 United States MH NIMH NIH HHS; Z01 AA000301 United States ImNIH Intramural NIH HHS; Z01 MH002865 United States ImNIH Intramural NIH HHS
المشرفين على المادة: 4TI98Z838E (Estradiol)
4G7DS2Q64Y (Progesterone)
0 (Estrogens)
تواريخ الأحداث: Date Created: 20230214 Date Completed: 20231102 Latest Revision: 20240218
رمز التحديث: 20240218
مُعرف محوري في PubMed: PMC10507674
DOI: 10.1038/s41380-023-01985-5
PMID: 36782063
قاعدة البيانات: MEDLINE
الوصف
تدمد:1476-5578
DOI:10.1038/s41380-023-01985-5