title: Biological risks for neurological abnormalities associated with hyperbilirubinemia.
abstract: Unconjugated bilirubin (UCB) injury to glial cells leads to the secretion of glutamate and elicits a typical inflammatory response. Release of pro-inflammatory cytokines may influence gliogenesis and neurogenesis, and lead to deficits in learning and memory. Glutamate metabolism dysregulation and overexpression of tumor necrosis factor-alpha (TNF-alpha) and interleukin (IL)-1beta are consistent with schizophrenia neuropathology. Recently, an increased prevalence of schizophrenia was reported in individuals with Gilbert's syndrome and among those who have had elevated levels of UCB in the neonatal life. In this review, we explore the reactivity of astrocytes, neurons and microglia to UCB, the cascade of events implicated in the immunostimulant effects of UCB, as well as the role of each nerve cell type and maturation state in the neuropathology of UCB. Identification of the signaling events promoted by UCB will be relevant for developing novel therapies that might reduce the risk of brain injury and disabilities.
authors.affiliation: Centro de Patogénese Molecular-UBMBE, Faculdade de Farmácia, University of Lisbon, Av. Forças Armadas, Lisbon, Portugal. dbrites@ff.ul.pt
authors.forename: D
authors.initials: D
authors.lastname: Brites
authors.forename: A
authors.initials: A
authors.lastname: Fernandes
authors.forename: A S
authors.initials: AS
authors.lastname: Falcão
authors.forename: A C
authors.initials: AC
authors.lastname: Gordo
authors.forename: R F M
authors.initials: RF
authors.lastname: Silva
authors.forename: M A
authors.initials: MA
authors.lastname: Brito
mesh_terms: D001253:Astrocytes / Q000502:physiology*; D001663:Bilirubin / Q000378:metabolism; D016923:Cell Death; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000503:physiopathology; D007647:Kernicterus / Q000503:physiopathology*; D020935:MAP Kinase Signaling System / Q000502:physiology; D017628:Microglia / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D009474:Neurons; D047990:TNF Receptor-Associated Factor 1 / Q000502:physiology
chemical_list: D016328:NF-kappa B; D047990:TNF Receptor-Associated Factor 1; D001663:Bilirubin