Unconjugated Bilirubin Restricts Oligodendrocyte Differentiation and Axonal Myelination

• Tipo: Artigo em Revista Científica Internacional
• Data: 2012

Autores

Barateiro, A (Autor) Outra; Miron, VE (Autor) Outra; Santos, SD (Autor) Outra; Relvas, JB (Autor) FMUP; Fernandes, A (Autor) Outra; ffrench-Constant, C (Autor) Outra; Brites, D (Autor) Outra

Revista

Título: Molecular Neurobiology

Vol. 47

Páginas: 632-644

ISSN: 0893-7648

Editora: Springer Nature

Indexação

ISI Web of Knowledge - 24 Citações

Scopus - 25 Citações

Outras Informações

ID Authenticus: P-00H-5D7

DOI: 10.1007/s12035-012-8364-8

Abstract (EN): High levels of serum unconjugated bilirubin (UCB) in newborns are associated with axonal damage and glial reactivity that may contribute to subsequent neurologic injury and encephalopathy (kernicterus). Impairments in myelination and white matter damage were observed at autopsy in kernicteric infants. We have recently reported that UCB reduces oligodendrocyte progenitor cell (OPC) survival in a pure OPC in vitro proliferative culture. Here, we hypothesized that neonatal hyperbilirubinemia may also impair oligodendrocyte (OL) maturation and myelination. We used an experimental model of hyperbilirubinemia that has been shown to mimic the pathophysiological conditions leading to brain dysfunction by unbound (free) UCB. Using primary cultures of OL, we demonstrated that UCB delays cell differentiation by increasing the OPC number and reducing the number of mature OL. This finding was combined with a downregulation of Olig1 mRNA levels and upregulation of Olig2 mRNA levels. Addition of UCB, prior to or during differentiation, impaired OL morphological maturation, extension of processes and cell diameter. Both conditions reduced active guanosine triphosphate (GTP)-bound Rac1 fraction. In myelinating co-cultures of dorsal root ganglia neurons and OL, UCB treatment prior to the onset of myelination decreased oligodendroglial differentiation and the number of myelinating OL, also observed when UCB was added after the onset of myelination. In both circumstances, UCB decreased the number of myelin internodes per OL, as well as the myelin internode length. Our studies demonstrate that increased concentrations of UCB compromise myelinogenesis, thereby elucidating a potential deleterious consequence of elevated UCB.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13