{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:39:54Z","timestamp":1778755194738,"version":"3.51.4"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T00:00:00Z","timestamp":1686787200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Neurosci."],"abstract":"<jats:p>Postpartum depression (PPD) is another type of depression, including emotional fluctuation, fatigue, and anxiety. Based on the specific event like giving birth, it can be speculated that PPD might have its specific mechanism. Here, we confirmed that dexamethasone (DEX) administration during pregnancy (gestational days 16\u201318) induced depressive- and anxiety-like behaviors in dam (DEX-dam) after weaning period (3 weeks). DEX-dam showed anxiety-like behaviors in open-field test (OFT) and light\u2013dark test (LD). In addition, DEX-dam exhibited depressive-like behaviors with the increased immobility time in forced swimming test (TST). Molecular analysis confirmed that microglia, rather than neurons, astrocytes, and oligodendrocytes, are involved in anxiety-\/depressive-like behaviors. Notably, <jats:italic>P2ry12<\/jats:italic>, homeostatic gene, and purinoceptor, along with hyper-ramified form, were reduced in the hippocampus of DEX-dam. In addition, we found that IL-10 mRNA was reduced in lymph nodes without alteration of pro-inflammatory cytokines, such as TNF-\u03b1, IL-1\u03b2, and IL-6. Interestingly, anxiety-\/depressive-like behaviors of DEX-dam were restored with the normalization of <jats:italic>P2ry12<\/jats:italic> and <jats:italic>IL-10<\/jats:italic> after 10 weeks postpartum without antidepressants. Our results propose that stress hormone elevation during pregnancy might be associated with PPD via microglial P2RY12 and peripheral IL-10.<\/jats:p>","DOI":"10.3389\/fncel.2023.1162966","type":"journal-article","created":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T05:37:56Z","timestamp":1686807476000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Possible involvement of microglial P2RY12 and peripheral IL-10 in postpartum depression"],"prefix":"10.3389","volume":"17","author":[{"given":"Hui-Ju","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Jung","family":"You","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soyoung","family":"Sung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chan","family":"Rim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min-Soo","family":"Kwon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-018-0063-8","article-title":"Inhibition in the amygdala anxiety circuitry","volume":"50","author":"Babaev","year":"2018","journal-title":"Exp. Mol. Med."},{"key":"B2","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/s41586-020-2777-8","article-title":"Negative feedback control of neuronal activity by microglia","volume":"586","author":"Badimon","year":"2020","journal-title":"Nature"},{"key":"B3","doi-asserted-by":"publisher","first-page":"909981","DOI":"10.3389\/fphar.2022.909981","article-title":"Antidepressant effects of NSAIDs in rodent models of depression-a systematic review","volume":"13","author":"Bay-Richter","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1056\/NEJMra073096","article-title":"Major depressive disorder","volume":"358","author":"Belmaker","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"917","DOI":"10.1016\/j.neubiorev.2021.05.018","article-title":"The kynurenine pathway in major depression: what we know and where to next","volume":"127","author":"Brown","year":"2021","journal-title":"Neurosci. Biobehav. Rev."},{"key":"B6","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1002\/ana.24304","article-title":"Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice","volume":"77","author":"Butovsky","year":"2015","journal-title":"Ann. Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/1742-2094-11-98","article-title":"Neuroinflammation and M2 microglia: the good, the bad, and the inflamed","volume":"11","author":"Cherry","year":"2014","journal-title":"J. Neuroinflammation"},{"key":"B8","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1192\/bjp.bp.111.100594","article-title":"White matter abnormalities and illness severity in major depressive disorder","volume":"201","author":"Cole","year":"2012","journal-title":"Br. J. Psychiatry"},{"key":"B9","doi-asserted-by":"publisher","first-page":"441","DOI":"10.1146\/annurev-immunol-051116-052358","article-title":"Microglia function in the central nervous system during health and neurodegeneration","volume":"35","author":"Colonna","year":"2017","journal-title":"Annu. Rev. Immunol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1038\/nrn2297","article-title":"From inflammation to sickness and depression: when the immune system subjugates the brain","volume":"9","author":"Dantzer","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1016\/j.biopsych.2009.09.033","article-title":"A meta-analysis of cytokines in major depression","volume":"67","author":"Dowlati","year":"2010","journal-title":"Biol. Psychiatry"},{"key":"B12","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1016\/j.bbi.2012.05.006","article-title":"Depressive symptoms enhance stress-induced inflammatory responses","volume":"31","author":"Fagundes","year":"2013","journal-title":"Brain Behav. Immun."},{"key":"B13","doi-asserted-by":"publisher","first-page":"15","DOI":"10.3892\/br.2016.807","article-title":"Role of inflammatory cytokines in depression: focus on interleukin-1beta","volume":"6","author":"Farooq","year":"2017","journal-title":"Biomed Rep"},{"key":"B14","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.neuroscience.2013.04.060","article-title":"Inflammatory cytokines in depression: neurobiological mechanisms and therapeutic implications","volume":"246","author":"Felger","year":"2013","journal-title":"Neuroscience"},{"key":"B15","doi-asserted-by":"publisher","first-page":"3766","DOI":"10.1111\/ejn.12752","article-title":"Gestational stress induces persistent depressive-like behavior and structural modifications within the postpartum nucleus accumbens","volume":"40","author":"Haim","year":"2014","journal-title":"Eur. J. Neurosci."},{"key":"B16","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1186\/s12974-015-0416-3","article-title":"IL-4\/10 prevents stress vulnerability following imipramine discontinuation","volume":"12","author":"Han","year":"2015","journal-title":"J. Neuroinflammation"},{"key":"B17","doi-asserted-by":"publisher","first-page":"30","DOI":"10.3389\/fpsyt.2019.00030","article-title":"Cytokine research in depression: principles, challenges, and open questions","volume":"10","author":"Himmerich","year":"2019","journal-title":"Front. Psychiatry"},{"key":"B18","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1111\/acps.12698","article-title":"Peripheral cytokine and chemokine alterations in depression: a meta-analysis of 82 studies","volume":"135","author":"Kohler","year":"2017","journal-title":"Acta Psychiatr. Scand."},{"key":"B19","doi-asserted-by":"publisher","first-page":"430","DOI":"10.3389\/fncel.2019.00430","article-title":"Loss of IL-10 Promotes differentiation of microglia to a M1 phenotype","volume":"13","author":"Laffer","year":"2019","journal-title":"Front. Cell. Neurosci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"592","DOI":"10.3109\/09540261.2013.813442","article-title":"Cytokines as biomarkers in depressive disorder: current standing and prospects","volume":"25","author":"Lichtblau","year":"2013","journal-title":"Int. Rev. Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","first-page":"143","DOI":"10.3389\/fnbeh.2014.00143","article-title":"Mice with altered BDNF signaling as models for mood disorders and antidepressant effects","volume":"8","author":"Lindholm","year":"2014","journal-title":"Front. Behav. Neurosci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/j.neuron.2008.06.019","article-title":"GABA(A)R plasticity during pregnancy: relevance to postpartum depression","volume":"59","author":"Maguire","year":"2008","journal-title":"Neuron"},{"key":"B23","doi-asserted-by":"publisher","first-page":"2299","DOI":"10.1016\/S0140-6736(18)31948-2","article-title":"Depression","volume":"392","author":"Malhi","year":"2018","journal-title":"Lancet"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1064","DOI":"10.1016\/S2215-0366(20)30255-8","article-title":"Neuroinflammation in psychiatric disorders: PET imaging and promising new targets","volume":"7","author":"Meyer","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"B25","doi-asserted-by":"publisher","first-page":"869779","DOI":"10.3389\/fncel.2022.869779","article-title":"Astroglia in the vulnerability to and maintenance of stress-mediated neuropathology and depression","volume":"16","author":"Miguel-Hidalgo","year":"2022","journal-title":"Front. Cell. Neurosci."},{"key":"B26","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.jad.2007.10.014","article-title":"Antenatal risk factors for postnatal depression: a large prospective study","volume":"108","author":"Milgrom","year":"2008","journal-title":"J. Affect. Disord."},{"key":"B27","doi-asserted-by":"publisher","first-page":"837","DOI":"10.1016\/S2215-0366(20)30357-6","article-title":"Trial failures of anti-inflammatory drugs in depression","volume":"7","author":"Miller","year":"2020","journal-title":"Lancet Psychiatry"},{"key":"B28","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1038\/nri.2015.5","article-title":"The role of inflammation in depression: from evolutionary imperative to modern treatment target","volume":"16","author":"Miller","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"105590","DOI":"10.1016\/j.psyneuen.2021.105590","article-title":"Animal models of postpartum depression revisited","volume":"136","author":"Mir","year":"2022","journal-title":"Psychoneuroendocrinology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1016\/j.psychres.2005.07.020","article-title":"Prepartum chronic ultramild stress increases corticosterone and estradiol levels in gestating mice: implications for postpartum depressive disorders","volume":"137","author":"Misdrahi","year":"2005","journal-title":"Psychiatry Res."},{"key":"B31","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/1742-2094-10-43","article-title":"Neuroinflammation and psychiatric illness","volume":"1","author":"Najjar","year":"2013","journal-title":"J. Neuroinflammation"},{"key":"B32","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1038\/sj.mp.4002148","article-title":"Lipopolysaccharide-induced depressive-like behavior is mediated by indoleamine 2,3-dioxygenase activation in mice","volume":"14","author":"O'connor","year":"2009","journal-title":"Mol. Psychiatry"},{"key":"B33","doi-asserted-by":"publisher","first-page":"16065","DOI":"10.1038\/nrdp.2016.65","article-title":"Major depressive disorder","volume":"2","author":"Otte","year":"2016","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B34","doi-asserted-by":"publisher","first-page":"22082","DOI":"10.1038\/s41598-020-79096-2","article-title":"Chronically infused angiotensin II induces depressive-like behavior via microglia activation","volume":"10","author":"Park","year":"2020","journal-title":"Sci. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1007\/s12035-018-1156-z","article-title":"Dexamethasone induces a specific form of ramified dysfunctional microglia","volume":"56","author":"Park","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/s13041-019-0492-x","article-title":"Microglial P2Y12 receptor regulates ventral hippocampal CA1 neuronal excitability and innate fear in mice","volume":"12","author":"Peng","year":"2019","journal-title":"Mol. Brain"},{"key":"B37","doi-asserted-by":"publisher","first-page":"219","DOI":"10.2174\/187152707780619326","article-title":"Gliogenesis and glial pathology in depression","volume":"6","author":"Rajkowska","year":"2007","journal-title":"CNS Neurol. Disord. Drug Targets"},{"key":"B38","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1038\/s41537-022-00280-6","article-title":"Microglia involvement in sex-dependent behaviors and schizophrenia occurrence in offspring with maternal dexamethasone exposure","volume":"8","author":"Rim","year":"2022","journal-title":"Schizophrenia"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.1016\/j.immuni.2020.09.018","article-title":"IL-10 prevents pathological microglia hyperactivation following peripheral endotoxin challenge","volume":"53","author":"Shemer","year":"2020","journal-title":"Immunity"},{"key":"B40","doi-asserted-by":"publisher","first-page":"659","DOI":"10.1002\/glia.20644","article-title":"Steroid hormone receptor expression and function in microglia","volume":"56","author":"Sierra","year":"2008","journal-title":"Glia"},{"key":"B41","doi-asserted-by":"publisher","first-page":"2177","DOI":"10.1056\/NEJMcp1607649","article-title":"Postpartum depression","volume":"375","author":"Stewart","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"B42","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1016\/j.neuroscience.2007.02.043","article-title":"Stress induced morphological microglial activation in the rodent brain: involvement of interleukin-18","volume":"146","author":"Sugama","year":"2007","journal-title":"Neuroscience"},{"key":"B43","doi-asserted-by":"publisher","first-page":"144","DOI":"10.3389\/fncel.2016.00144","article-title":"Linking activation of microglia and peripheral monocytic cells to the pathophysiology of psychiatric disorders","volume":"10","author":"Takahashi","year":"2016","journal-title":"Front. Cell. Neurosci."},{"key":"B44","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.jad.2010.09.013","article-title":"White matter abnormalities in major depression: evidence from post-mortem, neuroimaging and genetic studies","volume":"132","author":"Tham","year":"2011","journal-title":"J. Affect. Disord."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1016\/j.bbi.2010.02.001","article-title":"Chronic stress alters the density and morphology of microglia in a subset of stress-responsive brain regions","volume":"24","author":"Tynan","year":"2010","journal-title":"Brain Behav. Immun."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1262","DOI":"10.2174\/13894501113149990208","article-title":"Acute and chronic stress-induced disturbances of microglial plasticity, phenotype and function","volume":"14","author":"Walker","year":"2013","journal-title":"Curr. Drug Targets"},{"key":"B47","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.pnpbp.2017.04.008","article-title":"The recent progress in animal models of depression","volume":"77","author":"Wang","year":"2017","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry"},{"key":"B48","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1038\/s41398-021-01663-6","article-title":"Mapping global prevalence of depression among postpartum women","volume":"11","author":"Wang","year":"2021","journal-title":"Transl. Psychiatry"},{"key":"B49","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1007\/s12272-022-01369-3","article-title":"Possible role of arginase 1 positive microglia on depressive\/anxiety-like behaviors in atopic dermatitis mouse model","volume":"45","author":"Yang","year":"2022","journal-title":"Arch. Pharm. Res."},{"key":"B50","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1038\/s41398-023-02342-4","article-title":"A molecular characterization and clinical relevance of microglia-like cells derived from patients with panic disorder","volume":"13","author":"You","year":"2023","journal-title":"Transl. Psychiatry"},{"key":"B51","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1038\/s41380-020-00930-0","article-title":"Oligodendrocyte lineage cells and depression","volume":"26","author":"Zhou","year":"2021","journal-title":"Mol. Psychiatry"}],"container-title":["Frontiers in Cellular Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2023.1162966\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,15]],"date-time":"2023-06-15T05:37:58Z","timestamp":1686807478000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fncel.2023.1162966\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,15]]},"references-count":51,"alternative-id":["10.3389\/fncel.2023.1162966"],"URL":"https:\/\/doi.org\/10.3389\/fncel.2023.1162966","relation":{},"ISSN":["1662-5102"],"issn-type":[{"value":"1662-5102","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,15]]},"article-number":"1162966"}}