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There is mounting evidence that these behavioral phenotypes have origins\n                    <jats:italic>in utero<\/jats:italic>\n                    . Maternal microbes, inflammation, and serotonergic dysfunction have been implicated as potential mediators of the behavioral consequences of PNS; whether and how these systems interact is unclear. Here, we examine the effects of PNS\n                    <jats:italic>in utero<\/jats:italic>\n                    using late-gestation maternal restraint stress in wild-type (WT), germ-free (GF), and CCL2\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>\/<\/jats:sup>\n                    <jats:sup>\u2212<\/jats:sup>\n                    genetic knock-out (KO) mice. In WT mice, PNS leads to placental and fetal brain inflammation, including an elevation in the chemokine CCL2. This inflammation is largely absent in GF mice, indicating the critical role of maternal microbes in mediating immune processes\n                    <jats:italic>in utero<\/jats:italic>\n                    . Furthermore, PNS in the absence of CCL2 failed to increase pro-inflammatory cytokine IL-6 in the fetal brain. PNS offspring also exhibited deficits in sociability and anxiety-like behavior that were absent in CCL2\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>\/\u2212<\/jats:sup>\n                    PNS offspring. Tryptophan and serotonin (5-HT) were elevated in the WT PNS placenta, but not in CCL2\n                    <jats:sup>\u2212<\/jats:sup>\n                    <jats:sup>\/\u2212<\/jats:sup>\n                    and GF animals. Altogether, these findings suggest that a complex interaction between maternal microbes, inflammation, and serotonin metabolism regulates the emergence of behavioral abnormalities following PNS.\n                  <\/jats:p>","DOI":"10.1038\/s41398-020-00876-5","type":"journal-article","created":{"date-parts":[[2020,6,16]],"date-time":"2020-06-16T15:02:53Z","timestamp":1592319773000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":81,"title":["Prenatal stress causes intrauterine inflammation and serotonergic dysfunction, and long-term behavioral deficits through microbe- and CCL2-dependent mechanisms"],"prefix":"10.1038","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7234-3836","authenticated-orcid":false,"given":"Helen J.","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5698-5353","authenticated-orcid":false,"given":"Adrienne M.","family":"Antonson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Therese A.","family":"Rajasekera","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna M.","family":"Patterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael T.","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5559-0226","authenticated-orcid":false,"given":"Tamar L.","family":"Gur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,16]]},"reference":[{"key":"876_CR1","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.biopsych.2010.05.028","volume":"68","author":"TL Bale","year":"2010","unstructured":"Bale T. 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