Zonouzi, M;
Scafidi, J;
Li, P;
McEllin, B;
Edwards, J;
Dupree, JL;
Harvey, L;
... Gallo, V; + view all
(2015)
GABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury.
Nat Neurosci
, 18
(5)
pp. 674-682.
10.1038/nn.3990.
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GABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury.pdf - Accepted Version Download (3MB) | Preview |
Abstract
Diffuse white matter injury (DWMI), a leading cause of neurodevelopmental disabilities in preterm infants, is characterized by reduced oligodendrocyte formation. NG2-expressing 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.
| Type: | Article |
|---|---|
| Title: | GABAergic regulation of cerebellar NG2 cell development is altered in perinatal white matter injury. |
| Location: | United States |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1038/nn.3990 |
| Publisher version: | http://dx.doi.org/10.1038/nn.3990 |
| Additional information: | © 2015 Nature America, Inc. All rights reserved. |
| Keywords: | Action Potentials, Animals, Animals, Newborn, Asphyxia Neonatorum, Carbachol, Cell Count, Cells, Cultured, Cerebellum, Demyelinating Diseases, Disease Models, Animal, Female, GABA-A Receptor Antagonists, Hypoxia, Brain, Interneurons, Male, Mice, Mice, Knockout, Mice, Transgenic, Neural Stem Cells, Neurogenesis, Nipecotic Acids, Oligodendroglia, Purkinje Cells, Receptors, GABA-A, Solute Carrier Family 12, Member 2, Vigabatrin, White Matter, gamma-Aminobutyric Acid |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology |
| URI: | https://discovery.ucl.ac.uk/id/eprint/1464924 |
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