{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T20:55:35Z","timestamp":1791147335792,"version":"4.1.0"},"reference-count":60,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2010,10,5]],"date-time":"2010-10-05T00:00:00Z","timestamp":1286236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-sa\/3.0"},{"start":{"date-parts":[[2010,10,29]],"date-time":"2010-10-29T00:00:00Z","timestamp":1288310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2010,10,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Maternal infection during pregnancy with a wide range of RNA and DNA viruses is associated with increased risk for schizophrenia and autism in their offspring. A common feature in these exposures is that virus replication induces innate immunity through interaction with Toll-like receptors (TLRs). We employed a mouse model wherein pregnant mice were exposed to polyinosinic-polycytidylic acid [poly(I\u00a0\u00a0\u22c5\u00a0\u00a0C)], a synthetic, double-stranded RNA molecular mimic of replicating virus. Poly(I\u00a0\u22c5\u00a0C) inhibited embryonic neuronal stem cell replication and population of the superficial layers of the neocortex by neurons. Poly(I\u00a0\u22c5\u00a0C) also led to impaired neonatal locomotor development and abnormal sensorimotor gating responses in adult offspring. Using Toll-like receptor 3 (TLR3)-deficient mice, we established that these effects were dependent on TLR3. Inhibition of stem cell proliferation was also abrogated by pretreatment with the nonsteroidal anti-inflammatory drug (NSAID) carprofen, a cyclooxygenase (COX) inhibitor. Our findings provide insights into mechanisms by which maternal infection can induce subtle neuropathology and behavioral dysfunction, and they may suggest strategies for reducing the risk of neuropsychiatric disorders subsequent to prenatal exposures to pathogens and other triggers of innate immunity.<\/jats:p>\n                  <jats:p>\n                    <jats:bold>IMPORTANCE<\/jats:bold>\n                    Maternal infection during gestation increases the risk of neuropsychiatric disorders in their offspring. Furthermore, work in animal models indicates that pre- or neonatal infections with a wide range of viruses results in similar neurodevelopmental outcomes. These observations are consistent with a mechanism whereby damage is mediated through common pathways. Exposure of pregnant mice to polyinosinic-polycytidylic acid [poly(I\u00a0\u22c5\u00a0C)], a synthetic, double-stranded RNA (dsRNA) molecular mimic of replicating virus, inhibited embryonic neuronal stem cell replication and led to behavioral abnormalities in their offspring. These effects were mediated through TLR3 and abrogated by pretreatment with the nonsteroidal anti-inflammatory drug (NSAID) carprofen. Our findings provide insights into mechanisms by which maternal infection can induce subtle neuropathology and may suggest strategies for reducing the risk of neuropsychiatric diseases following exposures to infectious agents and other triggers of innate immunity during gestation.\n                  <\/jats:p>","DOI":"10.1128\/mbio.00176-10","type":"journal-article","created":{"date-parts":[[2010,10,5]],"date-time":"2010-10-05T21:10:46Z","timestamp":1286313046000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":80,"title":["Induction of Toll-Like Receptor 3-Mediated Immunity during Gestation Inhibits Cortical Neurogenesis and Causes Behavioral Disturbances"],"prefix":"10.1128","volume":"1","author":[{"given":"Joari","family":"De Miranda","sequence":"first","affiliation":[{"name":"Center for Infection and Immunity, Mailman School of Public Health, College of Physicians and Surgeons, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kavitha","family":"Yaddanapudi","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity, Mailman School of Public Health, College of Physicians and Surgeons, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mady","family":"Hornig","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity, Mailman School of Public Health, College of Physicians and Surgeons, Columbia University, New York, New York, USA"},{"name":"Department of Epidemiology, Mailman School of Public Health, College of Physicians and Surgeons, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Villar","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity, Mailman School of Public Health, College of Physicians and Surgeons, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Serge","sequence":"additional","affiliation":[{"name":"Center for Infection and Immunity, Mailman School of Public Health, College of Physicians and Surgeons, Columbia University, New York, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. 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