BDNF haploinsufficiency exerts a transient and regionally different influence upon oligodendroglial lineage cells during postnatal development

Nicholson, Madeline, Wood, Rhiannon J., Fletcher, Jessica L., van den Buuse, Maarten, Murray, Simon S., and Xiao, Junhua (2018) BDNF haploinsufficiency exerts a transient and regionally different influence upon oligodendroglial lineage cells during postnatal development. Molecular and Cellular Neuroscience, 90. pp. 12-21.

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Abstract

Brain-Derived Neurotrophic Factor (BDNF) plays important roles in promoting myelination in the developing central nervous system (CNS), however the influence it exerts on oligodendrocyte development in vivo remains unclear. As BDNF knockout mice die in the perinatal period, we undertook a systematic developmental analysis of oligodendroglial lineage cells within multiple CNS regions of BDNF heterozygous (HET) mice. Our data identify that BDNF heterozygosity results in transient reductions in oligodendroglial lineage cell density and progression that are largely restricted to the optic nerve, whereas the corpus callosum, cerebral cortex, basal forebrain and spinal cord white matter tracts are unaffected. In the first two postnatal weeks, BDNF HET mice exhibit reductions in the density of oligodendroglial lineage cells, oligodendrocyte precursor cells (OPCs) and postmitotic oligodendrocytes selectively in the optic nerve, but not in the brain or spinal cord white matter tracts. However, this normalizes later in development. The overall proportion of OPCs and mature oligodendrocytes remains unchanged from P9 to P30 in all CNS regions. This study identifies that BDNF exerts transient effects on oligodendroglial lineage cells selectively in the optic nerve during postnatal development. Taken together, this provides compelling evidence that BDNF haploinsufficiency exerts modest effects upon oligodendroglial cell density and lineage progression in vivo, suggesting its major role is restricted to promoting oligodendrocyte myelination.

Item ID: 55030
Item Type: Article (Research - C1)
ISSN: 1095-9327
Keywords: BDNF, oligodendrocyte, OPC, myelin, myelination, central nervous system
Copyright Information: © 2018 Elsevier Inc. All rights reserved.
Funders: National Health and Medical Research Council (NHMRC), University of Melbourne (UM), Australian Postgraduate Scholarship
Projects and Grants: NHMRC APP1058647
Date Deposited: 15 Aug 2018 07:39
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1101 Medical Biochemistry and Metabolomics > 110199 Medical Biochemistry and Metabolomics not elsewhere classified @ 70%
11 MEDICAL AND HEALTH SCIENCES > 1117 Public Health and Health Services > 111714 Mental Health @ 30%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970111 Expanding Knowledge in the Medical and Health Sciences @ 100%
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