NDLI: Unconjugated Bilirubin Restricts Oligodendrocyte Differentiation and Axonal Myelination

Content Provider	Springer Nature Link
Author	Barateiro, Andreia Miron, Veronique E. Santos, Sofia D. Relvas, João B. Fernandes, Adelaide ffrench Constant, Charles Brites, Dora
Copyright Year	2012
Abstract	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.
Starting Page	632
Ending Page	644
Page Count	13
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	47
Issue Number	2
e-ISSN	15591182
Language	English
Publisher	Humana Press Inc
Publisher Date	2012-10-21
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Oligodendrocytes Myelinating co-cultures Myelin deficits Unconjugated bilirubin Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Rat Cerebellar Slice Cultures Exposed to Bilirubin Evidence Reactive Gliosis, Excitotoxicity and Impaired Myelinogenesis that Is Prevented by AMPA and TNF-α Inhibitors

How Histone Deacetylases Control Myelination

GSK3β Promotes the Differentiation of Oligodendrocyte Precursor Cells via β-Catenin-Mediated Transcriptional Regulation

ER Stress, Mitochondrial Dysfunction and Calpain/JNK Activation are Involved in Oligodendrocyte Precursor Cell Death by Unconjugated Bilirubin

Thyroid Hormone Signaling in Oligodendrocytes: from Extracellular Transport to Intracellular Signal

Oligodendroglia and Myelin in Neurodegenerative Diseases: More Than Just Bystanders?

αB-Crystallin is Expressed in Myelinating Oligodendrocytes of the Developing and Adult Avian Retina

SCIRR39 Promotes Differentiation of Oligodendrocyte Precursor Cells and Regulates Expression of Myelin-Associated Inhibitory Factors

P38 Mitogen-Activated Protein Kinase Regulates Myelination

Unconjugated Bilirubin Restricts Oligodendrocyte Differentiation and Axonal Myelination

Similar Documents

Rat Cerebellar Slice Cultures Exposed to Bilirubin Evidence Reactive Gliosis, Excitotoxicity and Impaired Myelinogenesis that Is Prevented by AMPA and TNF-α Inhibitors

How Histone Deacetylases Control Myelination

GSK3β Promotes the Differentiation of Oligodendrocyte Precursor Cells via β-Catenin-Mediated Transcriptional Regulation

ER Stress, Mitochondrial Dysfunction and Calpain/JNK Activation are Involved in Oligodendrocyte Precursor Cell Death by Unconjugated Bilirubin

Thyroid Hormone Signaling in Oligodendrocytes: from Extracellular Transport to Intracellular Signal

Oligodendroglia and Myelin in Neurodegenerative Diseases: More Than Just Bystanders?

αB-Crystallin is Expressed in Myelinating Oligodendrocytes of the Developing and Adult Avian Retina

SCIRR39 Promotes Differentiation of Oligodendrocyte Precursor Cells and Regulates Expression of Myelin-Associated Inhibitory Factors

P38 Mitogen-Activated Protein Kinase Regulates Myelination

Unconjugated Bilirubin Restricts Oligodendrocyte Differentiation and Axonal Myelination