Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia
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 neonate...
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MDPI AG
2023-06-01
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| Online Access: | https://www.mdpi.com/2079-7737/12/6/834 |
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| author | John Paul Llido Emanuela Fioriti Devis Pascut Mauro Giuffrè Cristina Bottin Fabrizio Zanconati Claudio Tiribelli Silvia Gazzin |
| author_facet | John Paul Llido Emanuela Fioriti Devis Pascut Mauro Giuffrè Cristina Bottin Fabrizio Zanconati Claudio Tiribelli Silvia Gazzin |
| author_sort | John Paul Llido |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T02:45:03Z |
| format | Article |
| id | doaj.art-b608bc09813f4e6b8dddd6ef2fdc3e48 |
| institution | Directory Open Access Journal |
| issn | 2079-7737 |
| language | English |
| last_indexed | 2024-03-11T02:45:03Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biology |
| spelling | doaj.art-b608bc09813f4e6b8dddd6ef2fdc3e482023-11-18T09:23:12ZengMDPI AGBiology2079-77372023-06-0112683410.3390/biology12060834Bilirubin-Induced Transcriptomic Imprinting in Neonatal HyperbilirubinemiaJohn Paul Llido0Emanuela Fioriti1Devis Pascut2Mauro Giuffrè3Cristina Bottin4Fabrizio Zanconati5Claudio Tiribelli6Silvia Gazzin7Liver Brain Unit “Rita Moretti”, Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, 34149 Basovizza, ItalyLiver Brain Unit “Rita Moretti”, Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, 34149 Basovizza, ItalyLiver Cancer Unit, Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, 34149 Basovizza, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, ItalyDepartment of Medical, Surgical and Health Sciences, University of Trieste, 34149 Trieste, ItalyLiver Brain Unit “Rita Moretti”, Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, 34149 Basovizza, ItalyLiver Brain Unit “Rita Moretti”, Fondazione Italiana Fegato-Onlus, Bldg. Q, AREA Science Park, 34149 Basovizza, ItalyRecent 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.https://www.mdpi.com/2079-7737/12/6/834kernicterusbrain developmentmotor disabilitiesneurologic syndromecorplotgene clustering |
| spellingShingle | John Paul Llido Emanuela Fioriti Devis Pascut Mauro Giuffrè Cristina Bottin Fabrizio Zanconati Claudio Tiribelli Silvia Gazzin Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia Biology kernicterus brain development motor disabilities neurologic syndrome corplot gene clustering |
| title | Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia |
| title_full | Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia |
| title_fullStr | Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia |
| title_full_unstemmed | Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia |
| title_short | Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia |
| title_sort | bilirubin induced transcriptomic imprinting in neonatal hyperbilirubinemia |
| topic | kernicterus brain development motor disabilities neurologic syndrome corplot gene clustering |
| url | https://www.mdpi.com/2079-7737/12/6/834 |
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