Document Type

Article

Original Publication Date

2015

Journal/Book/Conference Title

Nature Neuroscience

Volume

18

Issue

5

DOI of Original Publication

10.1038/nn.3990

Comments

Originally published at http://dx.doi.org/10.1038/nn.3990

Date of Submission

December 2015

Abstract

Diffuse white matter injury (DWMI), a leading cause of neurodevelopmental disabilities in preterm infants, is characterized by reduced oligodendrocyte formation. Oligodendrocyte precursor cells (NG2-cells) are exposed to various extrinsic regulatory signals, including the neurotransmitter GABA. We investigated GABAergic signaling to cerebellar white matter NG2-cells in a mouse model of DWMI (chronic neonatal hypoxia). We found that hypoxia caused a loss of GABAA receptor-mediated synaptic input to NG2-cells, extensive proliferation of these cells and delayed oligodendrocyte maturation, leading to dysmyelination. Treatment of control mice with a GABAA receptor antagonist or deletion of the chloride-accumulating transporter NKCC1 mimicked the effects of hypoxia. Conversely, blockade of GABA catabolism or GABA uptake reduced NG2-cell numbers and increased the formation of mature oligodendrocytes both in control and hypoxic mice. Our results indicate that GABAergic signaling regulates NG2-cell differentiation and proliferation in vivo, and suggest that its perturbation is a key factor in DWMI.

Rights

Copyright © 2015, Rights Managed by Nature Publishing Group

Is Part Of

VCU Anatomy and Neurobiology Publications

Share

COinS
 
 
 
View graphic versionView graphic versionView graphic version