Bilirubin-Induced Transcriptomic Imprinting in Neonatal Hyperbilirubinemia.
brain development
corplot
gene clustering
histone acetylation
kernicterus
motor disabilities
neurologic syndrome
opisthotonus
schizophrenia
Journal
Biology
ISSN: 2079-7737
Titre abrégé: Biology (Basel)
Pays: Switzerland
ID NLM: 101587988
Informations de publication
Date de publication:
08 Jun 2023
08 Jun 2023
Historique:
received:
05
05
2023
revised:
01
06
2023
accepted:
06
06
2023
medline:
28
6
2023
pubmed:
28
6
2023
entrez:
28
6
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37372119
pii: biology12060834
doi: 10.3390/biology12060834
pmc: PMC10295065
pii:
doi:
Types de publication
Journal Article
Langues
eng
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