BDNF-TrkB Signaling in Lifelong Central Nervous System Myelination and Myelin Repair

Nicholson, Madeline; Yoo, SangWon; Craig, Georgina A.; Murray, Simon S.; Fletcher, Jessica L.

doi:10.1007/978-3-030-71519-9_219-1

Madeline Nicholson²^na1,
SangWon Yoo²^na1,
Georgina A. Craig²^na1,
Simon S. Murray²^na1 &
…
Jessica L. Fletcher^2,3^na1

132 Accesses

Abstract

Myelin, the lipid membrane that wraps around nerves, is a critical component of the peripheral (PNS) and central nervous systems (CNS) that enables rapid neurotransmission and is critical for brain function, including motor skill acquisition and working memory. In the CNS, myelin acquisition occurs rapidly during development, and myelin sheaths are made by oligodendrocytes in response to a host of extracellular factors, including brain-derived neurotrophic factor (BDNF) and neuronal activity. BDNF promotes CNS myelination by activating its TrkB receptor expressed by oligodendrocytes, and loss of oligodendrocyte TrkB delays myelin acquisition and reduces myelin sheath thickness. Myelin acquisition continues throughout life, and activity-dependent myelination appears to underpin myelin acquisition in adulthood. As local release of BDNF by neurons occurs in response to neuronal activity, BDNF has been identified as a potential modulator of activity-dependent myelin acquisition in addition to its known developmental effects via oligodendrocyte TrkB. As BDNF-TrkB signaling is a robust potentiator of myelination, it has also been identified as a therapeutic target to promote myelin repair in demyelinating diseases including multiple sclerosis (MS). This chapter summarizes the development of CNS myelination, its importance throughout life, and the role of BDNF-TrkB signaling in myelin development and activity-dependent myelin plasticity. The potential for increasing endogenous BDNF levels or targeting TrkB activation as a therapeutic strategy to promote myelin repair for demyelinating diseases such as multiple sclerosis is also summarized.

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Abbreviations

AMPA:: α-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid
APC:: Adenomatous polyposis coli
BDNF HET:: Heterozygous gene deletion of BDNF
BDNF:: Brain-derived neurotrophic factor
CC1:: Antibody clone CC1 against APC
CNPase:: 2′3’-Cyclic-nucleotide-3-phosphodiesterase
CNS:: Central nervous system
DHF:: 7,8-Dihydroxyflavone
EAE:: Experimental autoimmune encephalomyelitis
KO:: Gene knockout /deletion
K_v:: Voltage-gated potassium channel
MAG:: Myelin associated glycoprotein
MAPK-ERK1/2:: Mitogen activated protein kinase-extracellular signal related kinase 1/2
MBP:: Myelin basic protein
mGluR:: Metabotropic glutamate receptor
MOG:: Myelin oligodendrocyte glycoprotein
MS:: Multiple sclerosis
Na_V:: Voltage gated sodium channel
NGF:: Nerve growth factor
NMDA:: N-Methyl-D-aspartate
NT3:: Neurotrophin-3
NT4:: Neurotrophin-4
OPC:: Oligodendrocyte progenitor cell
p75^NTR:: Pan-neurotrophin receptor p75/nerve growth factor receptor
PDGFRα:: Platelet-derived growth factor receptor-α
PLCγ-PKC:: Phospholipase Cγ-protein kinase C
PLP1:: Proteolipid protein-1
PNS:: Peripheral nervous system
Trk:: Tropomyosin-related kinase

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Acknowledgments

Madeline Nicholson and Georgina A Craig are recipients of Australian Government Research Training Program Scholarships, and Madeline Nicholson, a University of Melbourne STRAPA Scholarship recipient. Sangwon Yoo is a recipient of a University of Melbourne Research Scholarship. This work was supported by the Assistant Secretary of Defense for Health Affairs, endorsed by the Department of Defense, USA, through the Multiple Sclerosis Research Program W81XWH-17-MSRP-IIRA under award no. MS170031 to Junhua Xiao and Simon Murray. Opinions, interpretations, conclusions, and recommendations are those of the authors and not necessarily endorsed by the Assistant Secretary of Defense for Health Affairs or Department of Defense (USA). We apologize to our colleagues whose citations were omitted due to space limitations.

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Madeline Nicholson and SangWon Yoo contributed equally

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Department of Anatomy and Physiology, School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Parkville, VIC, Australia
Madeline Nicholson, SangWon Yoo, Georgina A. Craig, Simon S. Murray & Jessica L. Fletcher
Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
Jessica L. Fletcher

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Madeline Nicholson
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SangWon Yoo
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Georgina A. Craig
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Simon S. Murray
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Jessica L. Fletcher
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Correspondence to Jessica L. Fletcher .

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Department of Biomedical Sciences, East Tennessee State University, Johnson City, TN, USA
Richard M. Kostrzewa

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Nicholson, M., Yoo, S., Craig, G.A., Murray, S.S., Fletcher, J.L. (2021). BDNF-TrkB Signaling in Lifelong Central Nervous System Myelination and Myelin Repair. In: Kostrzewa, R.M. (eds) Handbook of Neurotoxicity. Springer, Cham. https://doi.org/10.1007/978-3-030-71519-9_219-1

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DOI: https://doi.org/10.1007/978-3-030-71519-9_219-1
Received: 22 July 2021
Accepted: 23 July 2021
Published: 17 November 2021
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-71519-9
Online ISBN: 978-3-030-71519-9
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

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