{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,6]],"date-time":"2026-04-06T13:32:39Z","timestamp":1775482359521,"version":"3.50.1"},"reference-count":142,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2023,6,8]],"date-time":"2023-06-08T00:00:00Z","timestamp":1686182400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fondazione Italiana Fegato"},{"name":"Department of Science and Technology"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biology"],"abstract":"<jats:p>Recent findings indicated aberrant epigenetic control of the central nervous system (CNS) development in hyperbilirubinemic Gunn rats as an additional cause of cerebellar hypoplasia, the landmark of bilirubin neurotoxicity in rodents. Because the symptoms in severely hyperbilirubinemic human neonates suggest other regions as privileged targets of bilirubin neurotoxicity, we expanded the study of the potential impact of bilirubin on the control of postnatal brain development to regions correlating with human symptoms. Histology, transcriptomic, gene correlation, and behavioral studies were performed. The histology revealed widespread perturbation 9 days after birth, restoring in adulthood. At the genetic level, regional differences were noticed. Bilirubin affected synaptogenesis, repair, differentiation, energy, extracellular matrix development, etc., with transient alterations in the hippocampus (memory, learning, and cognition) and inferior colliculi (auditory functions) but permanent changes in the parietal cortex. Behavioral tests confirmed the presence of a permanent motor disability. The data correlate well both with the clinic description of neonatal bilirubin-induced neurotoxicity, as well as with the neurologic syndromes reported in adults that suffered neonatal hyperbilirubinemia. The results pave the way for better deciphering the neurotoxic features of bilirubin and evaluating deeply the efficacy of new therapeutic approaches against the acute and long-lasting sequels of bilirubin neurotoxicity.<\/jats:p>","DOI":"10.3390\/biology12060834","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T02:59:57Z","timestamp":1686279597000},"page":"834","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3912-437X","authenticated-orcid":false,"given":"John Paul","family":"Llido","sequence":"first","affiliation":[{"name":"Liver Brain Unit \u201cRita Moretti\u201d, Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, 34149 Basovizza, Italy"},{"name":"Department of Science and Technology, Philippine Council for Health Research and Development, Bicutan, Taguig City 1631, Philippines"},{"name":"Department of Life Sciences, University of Trieste, 34139 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Fioriti","sequence":"additional","affiliation":[{"name":"Liver Brain Unit \u201cRita Moretti\u201d, Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, 34149 Basovizza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0583-1973","authenticated-orcid":false,"given":"Devis","family":"Pascut","sequence":"additional","affiliation":[{"name":"Liver Cancer Unit, Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, 34149 Basovizza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9910-3514","authenticated-orcid":false,"given":"Mauro","family":"Giuffr\u00e8","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy"},{"name":"Department of Internal Medicine, Yale School of Medicine, Yale University, New Haven, CT 06510, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Bottin","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fabrizio","family":"Zanconati","sequence":"additional","affiliation":[{"name":"Department of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6596-7595","authenticated-orcid":false,"given":"Claudio","family":"Tiribelli","sequence":"additional","affiliation":[{"name":"Liver Brain Unit \u201cRita Moretti\u201d, Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, 34149 Basovizza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9403-3564","authenticated-orcid":false,"given":"Silvia","family":"Gazzin","sequence":"additional","affiliation":[{"name":"Liver Brain Unit \u201cRita Moretti\u201d, Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, 34149 Basovizza, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,6,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e000105","DOI":"10.1136\/bmjpo-2017-000105","article-title":"Burden of Severe Neonatal Jaundice: A Systematic Review and Meta-Analysis","volume":"1","author":"Slusher","year":"2017","journal-title":"BMJ Paediatr. 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