Please use this identifier to cite or link to this item:
https://doi.org/10.1016/j.jlr.2021.100147
Title: | Loss of ABCA8B decreases myelination by reducing oligodendrocyte precursor cells in mice | Authors: | Liu, Yiran Castano, David Girolamo, Francesco Trigueros-Motos, Laia Bae, Han-Gyu Neo, Suat Peng Oh, Jeongah Narayanaswamy, Pradeep Torta, Federico Rye, Kerry Anne Jo, Dong-Gyu Gunaratne, Jayantha Jung, Sangyong Virgintino, Daniela Singaraja, Roshni R |
Keywords: | Science & Technology Life Sciences & Biomedicine Biochemistry & Molecular Biology hypomyelination ABCA8 cerebellum animal models brain lipids lipid transfer proteins cholesterol/trafficking CSPG4 myelin disorders myelin sheath periodicity SPHINGOLIPID METABOLISM ALZHEIMERS-DISEASE NG2 PROTEOGLYCAN WHITE-MATTER DEFICIENCY BRAIN EXPRESSION ORGANIZATION CHOLESTEROL CEREBELLUM |
Issue Date: | Jan-2022 | Publisher: | ELSEVIER | Citation: | Liu, Yiran, Castano, David, Girolamo, Francesco, Trigueros-Motos, Laia, Bae, Han-Gyu, Neo, Suat Peng, Oh, Jeongah, Narayanaswamy, Pradeep, Torta, Federico, Rye, Kerry Anne, Jo, Dong-Gyu, Gunaratne, Jayantha, Jung, Sangyong, Virgintino, Daniela, Singaraja, Roshni R (2022-01). Loss of ABCA8B decreases myelination by reducing oligodendrocyte precursor cells in mice. JOURNAL OF LIPID RESEARCH 63 (1). ScholarBank@NUS Repository. https://doi.org/10.1016/j.jlr.2021.100147 | Abstract: | The myelin sheath, which is wrapped around axons, is a lipid-enriched structure produced by mature oligodendrocytes. Disruption of the myelin sheath is observed in several neurological diseases, such as multiple sclerosis. A crucial component of myelin is sphingomyelin, levels of which can be increased by ABCA8, a member of the ATP-binding cassette transporter family. ABCA8 is highly expressed in the cerebellum, specifically in oligodendroglia. However, whether ABCA8 plays a role in myelination and mechanisms that would underlie this role remain unknown. Here, we found that the absence of Abca8b, a mouse ortholog of ABCA8, led to decreased numbers of cerebellar oligodendrocyte precursor cells (OPCs) and mature oligodendrocytes in mice. We show that in oligodendrocytes, ABCA8 interacts with chondroitin sulfate proteoglycan 4 (CSPG4), a molecule essential for OPC proliferation, migration, and myelination. In the absence of Abca8b, localization of CSPG4 to the plasma membrane was decreased, contributing to reduced cerebellar CSPG4 expression. Cerebellar CSPG4+ OPCs were also diminished, leading to decreased mature myelinating oligodendrocyte numbers and cerebellar myelination levels in Abca8b-/- mice. In addition, electron microscopy analyses showed that the number of nonmyelinated cerebellar axons was increased, whereas cerebellar myelin thickness (g-ratio), myelin sheath periodicity, and axonal diameter were all decreased, indicative of disordered myelin ultrastructure. In line with disrupted cerebellar myelination, Abca8b-/- mice showed lower cerebellar conduction velocity and disturbed locomotion. In summary, ABCA8 modulates cerebellar myelination, in part through functional regulation of the ABCA8-interacting protein CSPG4. Our findings suggest that ABCA8 disruption may contribute to the pathophysiology of myelin disorders. | Source Title: | JOURNAL OF LIPID RESEARCH | URI: | https://scholarbank.nus.edu.sg/handle/10635/246652 | ISSN: | 0022-2275 1539-7262 |
DOI: | 10.1016/j.jlr.2021.100147 |
Appears in Collections: | Staff Publications Elements |
Show full item record
Files in This Item:
File | Description | Size | Format | Access Settings | Version | |
---|---|---|---|---|---|---|
Loss of ABCA8B decreases myelination by reducing oligodendrocyte precursor cells in mice.pdf | Published version | 6.01 MB | Adobe PDF | OPEN | None | View/Download |
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.