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Axon Degeneration: Which Method to Choose?

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Axon Degeneration

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2143))

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Abstract

Axons are diverse. They have different lengths, different branching patterns, and different biological roles. Methods to study axon degeneration are also diverse. The result is a bewildering range of experimental systems in which to study mechanisms of axon degeneration, and it is difficult to extrapolate from one neuron type and one method to another. The purpose of this chapter is to help readers to do this and to choose the methods most appropriate for answering their particular research question.

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References

  1. Conforti L, Gilley J, Coleman MP (2014) Wallerian degeneration: an emerging axon death pathway linking injury and disease. Nat Rev Neurosci 15:394–409. https://doi.org/10.1038/nrn3680

    Article  CAS  PubMed  Google Scholar 

  2. Van Helleputte L, Kater M, Cook DP et al (2018) Inhibition of histone deacetylase 6 (HDAC6) protects against vincristine-induced peripheral neuropathies and inhibits tumor growth. Neurobiol Dis 111:59–69. https://doi.org/10.1016/j.nbd.2017.11.011

    Article  CAS  PubMed  Google Scholar 

  3. Corey DR (2017) Nusinersen, an antisense oligonucleotide drug for spinal muscular atrophy. Nat Neurosci 20:497–499. https://doi.org/10.1038/nn.4508

    Article  CAS  PubMed  Google Scholar 

  4. Matsuda W, Furuta T, Nakamura KC et al (2009) Single nigrostriatal dopaminergic neurons form widely spread and highly dense axonal Arborizations in the Neostriatum. J Neurosci 29:444–453. https://doi.org/10.1523/JNEUROSCI.4029-08.2009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gilley J, Coleman MP (2010) Endogenous Nmnat2 is an essential survival factor for maintenance of healthy axons. PLoS Biol 8:e1000300. https://doi.org/10.1371/journal.pbio.1000300

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Nichols ALA, Meelkop E, Linton C et al (2016) The apoptotic engulfment machinery regulates axonal degeneration in C. elegans neurons. Cell Rep 14:1673–1683. https://doi.org/10.1016/j.celrep.2016.01.050

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Mack TGA, Reiner M, Beirowski B et al (2001) Wallerian degeneration of injured axons and synapses is delayed by a Ube4b/Nmnat chimeric gene. Nat Neurosci 4:1199–1206. https://doi.org/10.1038/nn770

    Article  CAS  PubMed  Google Scholar 

  8. Adalbert R, Gillingwater TH, Haley JE et al (2005) A rat model of slow Wallerian degeneration ( WldS ) with improved preservation of neuromuscular synapses. Eur J Neurosci 21:271–277. https://doi.org/10.1111/j.1460-9568.2004.03833.x

    Article  PubMed  Google Scholar 

  9. MacDonald JM, Beach MG, Porpiglia E et al (2006) The drosophila cell corpse engulfment receptor draper mediates glial clearance of severed axons. Neuron 50:869–881. https://doi.org/10.1016/j.neuron.2006.04.028

    Article  CAS  PubMed  Google Scholar 

  10. Martin SM, O’Brien GS, Portera-Cailliau C, Sagasti A (2010) Wallerian degeneration of zebrafish trigeminal axons in the skin is required for regeneration and developmental pruning. Development 137:3985–3994. https://doi.org/10.1242/dev.053611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kitay BM, McCormack R, Wang Y et al (2013) Mislocalization of neuronal mitochondria reveals regulation of Wallerian degeneration and NMNAT/WLDS-mediated axon protection independent of axonal mitochondria. Hum Mol Genet 22:1601–1614. https://doi.org/10.1093/hmg/ddt009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Stowers RS, Megeath LJ, Górska-Andrzejak J et al (2002) Axonal transport of mitochondria to synapses depends on Milton, a novel drosophila protein. Neuron 36:1063–1077. https://doi.org/10.1016/S0896-6273(02)01094-2

    Article  CAS  PubMed  Google Scholar 

  13. Milde S, Adalbert R, Elaman MH, Coleman MP (2015) Axonal transport declines with age in two distinct phases separated by a period of relative stability. Neurobiol Aging 36:971–981. https://doi.org/10.1016/j.neurobiolaging.2014.09.018

    Article  PubMed  PubMed Central  Google Scholar 

  14. Valdez G, Tapia JC, Lichtman JW et al (2012) Shared resistance to aging and ALS in neuromuscular junctions of specific muscles. PLoS One 7:e34640. https://doi.org/10.1371/journal.pone.0034640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Osterloh JM, Yang J, Rooney TM et al (2012) dSarm/Sarm1 is required for activation of an injury-induced axon death pathway. Science 337:481–484. https://doi.org/10.1126/science.1223899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Di Stefano M, Nascimento-Ferreira I, Orsomando G et al (2015) A rise in NAD precursor nicotinamide mononucleotide (NMN) after injury promotes axon degeneration. Cell Death Differ 22:731–742. https://doi.org/10.1038/cdd.2014.164

    Article  CAS  PubMed  Google Scholar 

  17. Di Stefano M, Loreto A, Orsomando G et al (2017) NMN deamidase delays Wallerian degeneration and rescues axonal defects caused by NMNAT2 deficiency in vivo. Curr Biol 27:784–794. https://doi.org/10.1016/j.cub.2017.01.070

    Article  CAS  PubMed  Google Scholar 

  18. Neukomm LJ, Burdett TC, Gonzalez MA et al (2014) Rapid in vivo forward genetic approach for identifying axon death genes in Drosophila. Proc Natl Acad Sci U S A 111:9965–9970. https://doi.org/10.1073/pnas.1406230111

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Harwell CS, Coleman MP (2016) Synaptophysin depletion and intraneuronal Aβ in organotypic hippocampal slice cultures from huAPP transgenic mice. Mol Neurodegener 11:44. https://doi.org/10.1186/s13024-016-0110-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Beirowski B, Berek L, Adalbert R et al (2004) Quantitative and qualitative analysis of Wallerian degeneration using restricted axonal labelling in YFP-H mice. J Neurosci Methods 134:23–35. https://doi.org/10.1016/j.jneumeth.2003.10.016

    Article  PubMed  Google Scholar 

  21. Huppke P, Wegener E, Gilley J et al (2019) Homozygous NMNAT2 mutation in sisters with polyneuropathy and erythromelalgia. Exp Neurol 320:112958. https://doi.org/10.1016/j.expneurol.2019.112958

    Article  CAS  PubMed  Google Scholar 

  22. Lukacs M, Gilley J, Zhu Y et al (2019) Severe biallelic loss-of-function mutations in nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) in two fetuses with fetal akinesia deformation sequence. Exp Neurol 320:112961. https://doi.org/10.1016/j.expneurol.2019.112961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Navarro SJ, Trinh T, Lucas CA et al (2012) The C57BL/6J mouse strain background modifies the effect of a mutation in Bcl2l2. G3 (Bethesda) 2:99–102. https://doi.org/10.1534/g3.111.000778

    Article  CAS  Google Scholar 

  24. Lunn ER, Perry VH, Brown MC et al (1989) Absence of Wallerian degeneration does not hinder regeneration in peripheral nerve. Eur J Neurosci 1:27–33. https://doi.org/10.1111/j.1460-9568.1989.tb00771.x

    Article  CAS  PubMed  Google Scholar 

  25. Gilley J, Adalbert R, Yu G, Coleman MP (2013) Rescue of Peripheral and CNS axon defects in mice lacking NMNAT2. J Neurosci 33:13410–13424. https://doi.org/10.1523/JNEUROSCI.1534-13.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Ferri A, Sanes JR, Coleman MP et al (2003) Inhibiting axon degeneration and synapse loss attenuates apoptosis and disease progression in a mouse model of Motoneuron disease. Curr Biol 13:669–673. https://doi.org/10.1016/S0960-9822(03)00206-9

    Article  CAS  PubMed  Google Scholar 

  27. Gilley J, Ribchester RR, Coleman MP (2017) Sarm1 deletion, but not Wld S, confers lifelong Rescue in a Mouse Model of severe Axonopathy. Cell Rep 21:10–16. https://doi.org/10.1016/j.celrep.2017.09.027

  28. Geisler S, Doan RA, Strickland A et al (2016) Prevention of vincristine-induced peripheral neuropathy by genetic deletion of SARM1 in mice. Brain 139:3092–3108. https://doi.org/10.1093/brain/aww251

    Article  PubMed  PubMed Central  Google Scholar 

  29. Geisler S, Doan RA, Cheng GC et al (2019) Vincristine and bortezomib use distinct upstream mechanisms to activate a common SARM1-dependent axon degeneration program. JCI Insight 4:e129920. https://doi.org/10.1172/jci.insight.129920

    Article  PubMed Central  Google Scholar 

  30. Turkiew E, Falconer D, Reed N, Höke A (2017) Deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy: deletion of Sarm1 gene is neuroprotective in two models of peripheral neuropathy. J Peripher Nerv Syst 22:162–171. https://doi.org/10.1111/jns.12219

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gilley J, Mayer PR, Yu G, Coleman MP (2019) Low levels of NMNAT2 compromise axon development and survival. Hum Mol Genet 28:448–458. https://doi.org/10.1093/hmg/ddy356

    Article  CAS  PubMed  Google Scholar 

  32. Milde S, Gilley J, Coleman MP (2013) Subcellular localization determines the stability and axon protective capacity of axon survival factor Nmnat2. PLoS Biol 11:e1001539. https://doi.org/10.1371/journal.pbio.1001539

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Buonvicino D, Mazzola F, Zamporlini F et al (2018) Identification of the Nicotinamide salvage pathway as a new Toxification route for antimetabolites. Cell Chem Biol 25:471–482.e7. https://doi.org/10.1016/j.chembiol.2018.01.012

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Clinical Neurosciences, John van Geest Centre for Brain Repair, University of Cambridge, Cambridge, UK

    Michael P. Coleman

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  1. Michael P. Coleman
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Correspondence to Michael P. Coleman .

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Editors and Affiliations

  1. Department of Biochemistry, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY, USA

    Elisabetta Babetto

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Coleman, M.P. (2020). Axon Degeneration: Which Method to Choose?. In: Babetto, E. (eds) Axon Degeneration. Methods in Molecular Biology, vol 2143. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-0585-1_1

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  • DOI: https://doi.org/10.1007/978-1-0716-0585-1_1

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-0584-4

  • Online ISBN: 978-1-0716-0585-1

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