{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:55:14Z","timestamp":1792122914390,"version":"4.4.0"},"posted":{"date-parts":[[2025,10,1]]},"group-title":"Neuroscience","reference-count":21,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T00:00:00Z","timestamp":1759276800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01NS088566"],"award-info":[{"award-number":["R01NS088566"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P50HD105351"],"award-info":[{"award-number":["P50HD105351"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["S10OD030322"],"award-info":[{"award-number":["S10OD030322"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000011","name":"Howard Hughes Medical Institute","doi-asserted-by":"crossref","award":["Gilliam Fellowship"],"award-info":[{"award-number":["Gilliam Fellowship"]}],"id":[{"id":"10.13039\/100000011","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100001033","name":"The Jane Coffin Childs Memorial Fund for Medical Research","doi-asserted-by":"crossref","award":["Postdoctoral Fellowship"],"award-info":[{"award-number":["Postdoctoral Fellowship"]}],"id":[{"id":"10.13039\/100001033","id-type":"DOI","asserted-by":"crossref"}]},{"award":["Kirby Innovation Award"],"award-info":[{"award-number":["Kirby Innovation Award"]}],"id":[{"id":"https:\/\/ror.org\/03kz2rg33","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>\n                  <jats:bold>Abstract<\/jats:bold>\n                <\/jats:title>\n                <jats:p>\n                  Classic serotonergic psychedelics engage 5-HT receptors throughout the nervous system, but how maternal exposure intersects with embryonic brain interfaces is poorly defined. Here we tested in mice whether maternally administered lysergic acid diethylamide (LSD) accesses embryonic cerebrospinal fluid (CSF) and whether embryonic choroid plexus (ChP) \u2013 a CSF-secreting epithelium enriched for\n                  <jats:italic>Htr2c<\/jats:italic>\n                  \u2013 mounts an acute response. Following a single maternal injection (0.3 mg kg\u207b\u00b9, subcutaneous), LSD was detectable in embryonic CSF within 5\u201315 minutes at E12.5 and E16.5. Thirty minutes after maternal dosing, LSD induced Fos in embryonic ChP across ventricles and was accompanied by rapid apical remodeling and increased embryonic CSF protein. In parallel cohorts, psilocybin, 5-MeO-DMT, and the 5-HT\u2082C agonist WAY-161503 elicited a similar Fos response in ChP. Prenatal LSD exposure during mid-gestation was associated with altered S1 cortical cellularity and projection-neuron subtype marker composition at P8; regimen-dependent effects included male-biased changes in SATB2\u207a and CTIP2\u207a populations after repeated exposure. In adulthood, offspring exhibited modest, male-predominant reductions in prepulse inhibition and increased rotational stereotypy. Together, these data identify embryonic CSF as a rapidly accessible compartment for maternal LSD and support a model in which serotonergic agonists can acutely engage ChP epithelium during cerebral cortical development.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Significance<\/jats:title>\n                  <jats:p>Psychedelic use during pregnancy is increasing, but the speed and extent to which these drugs access the embryonic CNS remain unknown. We show that a single maternal dose of LSD appears in mouse embryonic cerebrospinal fluid within five minutes and provokes an immediate response in the choroid plexus, a serotonin receptor-rich epithelium that regulates CSF composition. Psilocybin, 5-MeO-DMT, and a selective 5-HT\u2082C agonist trigger a similar response. Mid-gestational exposure alters cortical neuron composition in neonates and produces persistent behavioral abnormalities in adult offspring, including stereotypies evident from weaning. These data reveal that maternal serotonergic agonists rapidly access embryonic CSF, acutely activate choroid plexus epithelium, and are associated with lasting changes in cortical composition and offspring behavior.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.09.30.677638","type":"posted-content","created":{"date-parts":[[2025,10,1]],"date-time":"2025-10-01T09:20:26Z","timestamp":1759310426000},"source":"Crossref","is-referenced-by-count":2,"title":["Gestational LSD exposure in mouse rapidly reaches embryonic CSF and is associated with altered choroid plexus signaling, cerebral cortical development, and offspring behavior"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4562-500X","authenticated-orcid":false,"given":"Ya\u2019el","family":"Courtney","sequence":"first","affiliation":[{"name":"Department of Pathology, Boston Children\u2019s Hospital and Harvard Medical School; Boston, MA, USA"},{"name":"Program in Neuroscience, Harvard Medical School; Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josephine M.","family":"Anderson","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Wisconsin; Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lagares-Linares","sequence":"additional","affiliation":[{"name":"Department of Pathology, Boston Children\u2019s Hospital and Harvard Medical School; Boston, MA, USA"},{"name":"Program in Neuroscience, Harvard Medical School; Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cody J.","family":"Wenthur","sequence":"additional","affiliation":[{"name":"School of Pharmacy, University of Wisconsin; Madison, WI, USA"},{"name":"Transdisciplinary Center for Research in Psychoactive Substances, University of Wisconsin; Madison, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria K.","family":"Lehtinen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Boston Children\u2019s Hospital and Harvard Medical School; Boston, MA, USA"},{"name":"Program in Neuroscience, Harvard Medical School; Boston, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026040402301069000_2025.09.30.677638v2.1","doi-asserted-by":"crossref","unstructured":"Bonnin A , Goeden N , Chen K , Wilson ML , King J , Shih JC , Blakely RD , Deneris ES , Levitt P (2011) A transient placental source of serotonin for the fetal forebrain. 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