Dysfunction of the oligodendrocytes in amyotrophic lateral sclerosis

Zhenxiang Gong; Li Ba; Min Zhang

doi:10.7555/JBR.36.20220009

Volume 36 Issue 5

Sep. 2022

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Zhenxiang Gong, Li Ba, Min Zhang. Dysfunction of the oligodendrocytes in amyotrophic lateral sclerosis[J]. The Journal of Biomedical Research, 2022, 36(5): 336-342. doi: 10.7555/JBR.36.20220009

Citation:

Zhenxiang Gong, Li Ba, Min Zhang. Dysfunction of the oligodendrocytes in amyotrophic lateral sclerosis[J]. The Journal of Biomedical Research, 2022, 36(5): 336-342. doi: 10.7555/JBR.36.20220009

Zhenxiang Gong, Li Ba, Min Zhang. Dysfunction of the oligodendrocytes in amyotrophic lateral sclerosis[J]. The Journal of Biomedical Research, 2022, 36(5): 336-342. doi: 10.7555/JBR.36.20220009

Citation:

Zhenxiang Gong, Li Ba, Min Zhang. Dysfunction of the oligodendrocytes in amyotrophic lateral sclerosis[J]. The Journal of Biomedical Research, 2022, 36(5): 336-342. doi: 10.7555/JBR.36.20220009

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Dysfunction of the oligodendrocytes in amyotrophic lateral sclerosis

doi: 10.7555/JBR.36.20220009

Department of Neurology and Psychiatry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China

Funds: The current study was supported by the innovative population project of Hubei Province (Grant No. 2019CFA030) and the clinical research project of Bethune Charitable Foundation, China.

More Information

Corresponding author: Min Zhang, Department of Neurology and Psychiatry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Road, Qiaokou District, Wuhan, Hubei 430030, China. Tel: +86-27-83663895, E-mail: zhang_min_3464@126.com
Received: 2022-01-10
Revised: 2022-06-13
Accepted: 2022-07-04

Published: 2022-08-28

Issue Date: 2022-09-28

Abstract

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by irreversible deterioration of upper and lower motor neurons (MNs). Previously, studies on the involvement of glial cells in the pathogenic process of ALS have mainly revolved around astrocytes and microglia. And oligodendrocytes (OLs) have only recently been highlighted. Grey matter demyelination within the motor cortex and proliferation of the oligodendrocyte precursor cells (OPCs) was observed in ALS patients. The selective ablation of mutant SOD1 (the dysfunctional superoxide dismutase) from the oligodendrocyte progenitors after birth significantly delayed disease onset and prolonged the overall survival in ALS mice model (SOD1^G37R). In this study, we review the several mechanisms of oligodendrocyte dysfunction involved in the pathological process of myelin damage and MNs death during ALS. Particularly, we examined the insufficient local energy supply from OLs to axons, impaired differentiation from OPCs into OLs mediated by oxidative stress damage, and inflammatory injury to the OLs. Since increasing evidence depicted that ALS is not a disease limited to MNs damage, exploring the mechanisms by which oligodendrocyte dysfunction is involved in MNs death would contribute to a more comprehensive understanding of ALS and identifying potential drug targets.
- oligodendrocytes,
- amyotrophic lateral sclerosis,
- energy metabolism,
- oxidative stress,
- neuroinflammation

CLC number: R744.8, Document code: A
The authors reported no conflict of interests.
^△These authors contributed to this work equally.

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References(68)

References

[1]	Hardiman O, Al-Chalabi A, Chio A, et al. Amyotrophic lateral sclerosis[J]. Nat Rev Dis Primers, 2017, 3: 17071. doi: 10.1038/nrdp.2017.71
[2]	Hardiman O, Van Den Berg LH, Kiernan MC. Clinical diagnosis and management of amyotrophic lateral sclerosis[J]. Nat Rev Neurol, 2011, 7(11): 639–649. doi: 10.1038/nrneurol.2011.153
[3]	Rothstein JD. Edaravone: A new drug approved for ALS[J]. Cell, 2017, 171(4): 725. doi: 10.1016/j.cell.2017.10.011
[4]	Cerveró A, Casado A, Riancho J. Retinal changes in amyotrophic lateral sclerosis: looking at the disease through a new window[J]. J Neurol, 2021, 268(6): 2083–2089.
[5]	Robberecht W, Philips T. The changing scene of amyotrophic lateral sclerosis[J]. Nat Rev Neurosci, 2013, 14(4): 248–264.
[6]	Boillée S, Yamanaka K, Lobsiger CS, et al. Onset and progression in inherited ALS determined by motor neurons and microglia[J]. Science, 2006, 312(5778): 1389–1392. doi: 10.1126/science.1123511
[7]	Yamanaka K, Chun SJ, Boillee S, et al. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis[J]. Nat Neurosci, 2008, 11(3): 251–253. doi: 10.1038/nn2047
[8]	Fünfschilling U, Supplie LM, Mahad D, et al. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity[J]. Nature, 2012, 485(7399): 517–521. doi: 10.1038/nature11007
[9]	Puentes F, Malaspina A, Van Noort JM, et al. Non-neuronal cells in ALS: Role of glial, immune cells and blood-CNS barriers[J]. Brain Pathol, 2016, 26(2): 248–257. doi: 10.1111/bpa.12352
[10]	Boillée S, Velde C V, Cleveland D W. ALS: a disease of motor neurons and their nonneuronal neighbors[J]. Neuron, 2006, 52(1): 39–59. doi: 10.1016/j.neuron.2006.09.018
[11]	Lino MM, Schneider C, Caroni P. Accumulation of SOD1 mutants in postnatal motoneurons does not cause motoneuron pathology or motoneuron disease[J]. J Neurosci, 2002, 22(12): 4825–4832. doi: 10.1523/JNEUROSCI.22-12-04825.2002
[12]	Pramatarova A, Laganière J, Roussel J, et al. Neuron-specific expression of mutant superoxide dismutase 1 in transgenic mice does not lead to motor impairment[J]. J Neurosci, 2001, 21(10): 3369–3374. doi: 10.1523/JNEUROSCI.21-10-03369.2001
[13]	Clement AM, Nguyen MD, Roberts EA, et al. Wild-type nonneuronal cells extend survival of SOD1 mutant motor neurons in ALS mice[J]. Science, 2003, 302(5642): 113–117. doi: 10.1126/science.1086071
[14]	Beers DR, Henkel JS, Xiao Q, et al. Wild-type microglia extend survival in PU. 1 knockout mice with familial amyotrophic lateral sclerosis[J]. Proc Natl Acad Sci U S A, 2006, 103(43): 16021–16026. doi: 10.1073/pnas.0607423103
[15]	Stadelmann C, Timmler S, Barrantes-Freer A, et al. Myelin in the central nervous system: structure, function, and pathology[J]. Physiol Rev, 2019, 99(3): 1381–1431. doi: 10.1152/physrev.00031.2018
[16]	Uyeda A, Muramatsu R. molecular mechanisms of central nervous system axonal regeneration and remyelination: a review[J]. Int J Mol Sci, 2020, 21(21): 8116. doi: 10.3390/ijms21218116
[17]	Saab AS, Nave KA. Myelin dynamics: protecting and shaping neuronal functions[J]. Curr Opin Neurobiol, 2017, 47: 104–112. doi: 10.1016/j.conb.2017.09.013
[18]	Saez I, Duran J, Sinadinos C, et al. Neurons have an active glycogen metabolism that contributes to tolerance to hypoxia[J]. J Cereb Blood Flow Metab, 2014, 34(6): 945–955. doi: 10.1038/jcbfm.2014.33
[19]	Zeis T, Enz L, Schaeren-Wiemers N. The immunomodulatory oligodendrocyte[J]. Brain Res, 2016, 1641: 139–148. doi: 10.1016/j.brainres.2015.09.021
[20]	Peferoen L, Kipp M, Van Der Valk P, et al. Oligodendrocyte-microglia cross-talk in the central nervous system[J]. Immunology, 2014, 141(3): 302–313. doi: 10.1111/imm.12163
[21]	Kang SH, Li Y, Fukaya M, et al. Degeneration and impaired regeneration of gray matter oligodendrocytes in amyotrophic lateral sclerosis[J]. Nat Neurosci, 2013, 16(5): 571–579. doi: 10.1038/nn.3357
[22]	Philips T, Bento-Abreu A, Nonneman A, et al. Oligodendrocyte dysfunction in the pathogenesis of amyotrophic lateral sclerosis[J]. Brain, 2013, 136(Pt 2): 471–482. doi: 10.1093/brain/aws339
[23]	Bonfanti E, Bonifacino T, Raffaele S, et al. Abnormal upregulation of GPR17 receptor contributes to oligodendrocyte dysfunction in SOD1 G93A mice[J]. Int J Mol Sci, 2020, 21(7): 2395. doi: 10.3390/ijms21072395
[24]	Kim S, Chung AY, Na JE, et al. Myelin degeneration induced by mutant superoxide dismutase 1 accumulation promotes amyotrophic lateral sclerosis[J]. Glia, 2019, 67(10): 1910–1921. doi: 10.1002/glia.23669
[25]	Dienel GA. Brain glucose metabolism: integration of energetics with function[J]. Physiol Rev, 2019, 99(1): 949–1045. doi: 10.1152/physrev.00062.2017
[26]	Bélanger M, Allaman I, Magistretti PJ. Brain energy metabolism: focus on astrocyte-neuron metabolic cooperation[J]. Cell Metab, 2011, 14(6): 724–738. doi: 10.1016/j.cmet.2011.08.016
[27]	Allaman I, Bélanger M, Magistretti PJ. Astrocyte-neuron metabolic relationships: for better and for worse[J]. Trends Neurosci, 2011, 34(2): 76–87. doi: 10.1016/j.tins.2010.12.001
[28]	Meyer N, Richter N, Fan Z, et al. Oligodendrocytes in the mouse corpus callosum maintain axonal function by delivery of glucose[J]. Cell Rep, 2018, 22(9): 2383–2394. doi: 10.1016/j.celrep.2018.02.022
[29]	Maglione M, Tress O, Haas B, et al. Oligodendrocytes in mouse corpus callosum are coupled via gap junction channels formed by connexin47 and connexin32[J]. Glia, 2010, 58(9): 1104–1117. doi: 10.1002/glia.20991
[30]	Cui Y, Masaki K, Yamasaki R, et al. Extensive dysregulations of oligodendrocytic and astrocytic connexins are associated with disease progression in an amyotrophic lateral sclerosis mouse model[J]. J Neuroinflammation, 2014, 11: 42. doi: 10.1186/1742-2094-11-42
[31]	Pellerin L, Bouzier-Sore AK, Aubert A, et al. Activity-dependent regulation of energy metabolism by astrocytes: an update[J]. Glia, 2007, 55(12): 1251–1262. doi: 10.1002/glia.20528
[32]	Bélanger M, Magistretti J. The role of astroglia in neuroprotection[J]. Dialogues Clin Neurosci, 2009, 11(3): 281–295. doi: 10.31887/DCNS.2009.11.3/mbelanger
[33]	Saab AS, Tzvetavona I, Trevisiol A, et al. Oligodendroglial NMDA receptors regulate glucose import and axonal energy metabolism[J]. Neuron, 2016, 91(1): 119–132. doi: 10.1016/j.neuron.2016.05.016
[34]	Rinholm JE, Hamilton NB, Kessaris N, et al. Regulation of oligodendrocyte development and myelination by glucose and lactate[J]. J Neurosci, 2011, 31(2): 538–548. doi: 10.1523/JNEUROSCI.3516-10.2011
[35]	Lee Y, Morrison BM, Li Y, et al. Oligodendroglia metabolically support axons and contribute to neurodegeneration[J]. Nature, 2012, 487(7408): 443–448. doi: 10.1038/nature11314
[36]	Roosterman D, Cottrell GS, Roosterman D, et al. Astrocytes and neurons communicate via a monocarboxylic acid shuttle[J]. AIMS Neurosci, 2020, 7(2): 94–106. doi: 10.3934/Neuroscience.2020007
[37]	Zielke HR, Zielke CL, Baab PJ. Direct measurement of oxidative metabolism in the living brain by microdialysis: a review[J]. J Neurochem, 2009, 109(Suppl 1): 24–29.
[38]	Morena J, Gupta A, Hoyle JC. Charcot-marie-tooth: from molecules to therapy[J]. Int J Mol Sci, 2019, 20(14): 3419. doi: 10.3390/ijms20143419
[39]	Kim MS, Gloor GB, Bai DL. The distribution and functional properties of Pelizaeus-Merzbacher-like disease-linked Cx47 mutations on Cx47/Cx47 homotypic and Cx47/Cx43 heterotypic gap junctions[J]. Biochem J, 2013, 452(2): 249–258. doi: 10.1042/BJ20121821
[40]	Gandhi GK, Cruz NF, Ball KK, et al. Astrocytes are poised for lactate trafficking and release from activated brain and for supply of glucose to neurons[J]. J Neurochem, 2009, 111(2): 522–536. doi: 10.1111/j.1471-4159.2009.06333.x
[41]	Barber SC, Shaw PJ. Oxidative stress in ALS: key role in motor neuron injury and therapeutic target[J]. Free Radic Biol Med, 2010, 48(5): 629–641. doi: 10.1016/j.freeradbiomed.2009.11.018
[42]	Jaiswal MK. Riluzole and edaravone: A tale of two amyotrophic lateral sclerosis drugs[J]. Med Res Rev, 2019, 39(2): 733–748. doi: 10.1002/med.21528
[43]	Fernandez-Castaneda A, Gaultier A. Adult oligodendrocyte progenitor cells - Multifaceted regulators of the CNS in health and disease[J]. Brain Behav Immun, 2016, 57: 1–7. doi: 10.1016/j.bbi.2016.01.005
[44]	Kuhn S, Gritti L, Crooks D, et al. Oligodendrocytes in development, myelin generation and beyond[J]. Cells, 2019, 8(11): 1424. doi: 10.3390/cells8111424
[45]	Trist BG, Hilton JB, Hare DJ, et al. Superoxide dismutase 1 in health and disease: how a frontline antioxidant becomes neurotoxic[J]. Angew Chem Int Ed, 2021, 60(17): 9215–9246. doi: 10.1002/anie.202000451
[46]	Veiga S, Ly J, Chan PH, et al. SOD1 overexpression improves features of the oligodendrocyte precursor response in vitro[J]. Neurosci Lett, 2011, 503(1): 10–14. doi: 10.1016/j.neulet.2011.07.053
[47]	Baud O, Haynes RF, Wang H, et al. Developmental up-regulation of MnSOD in rat oligodendrocytes confers protection against oxidative injury[J]. Eur J Neurosci, 2004, 20(1): 29–40. doi: 10.1111/j.0953-816X.2004.03451.x
[48]	Kansanen E, Kuosmanen SM, Leinonen H, et al. The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer[J]. Redox Biol, 2013, 1(1): 45–49. doi: 10.1016/j.redox.2012.10.001
[49]	Dinkova-Kostova AT, Holtzclaw WD, Wakabayashi N. Keap1, the sensor for electrophiles and oxidants that regulates the phase 2 response, is a zinc metalloprotein[J]. Biochemistry, 2005, 44(18): 6889–6899. doi: 10.1021/bi047434h
[50]	Sarlette A, Krampfl K, Grothe C, et al. Nuclear erythroid 2-related factor 2-antioxidative response element signaling pathway in motor cortex and spinal cord in amyotrophic lateral sclerosis[J]. J Neuropathol Exp Neurol, 2008, 67(11): 1055–1062. doi: 10.1097/NEN.0b013e31818b4906
[51]	Nellessen A, Nyamoya S, Zendedel A, et al. Nrf2 deficiency increases oligodendrocyte loss, demyelination, neuroinflammation and axonal damage in an MS animal model[J]. Metab Brain Dis, 2020, 35(2): 353–362. doi: 10.1007/s11011-019-00488-z
[52]	Minj E, Upadhayay S, Mehan S. Nrf2/HO-1 signaling activator acetyl-11-keto-beta Boswellic Acid (AKBA)-mediated neuroprotection in methyl mercury-induced experimental model of ALS[J]. Neurochem Res, 2021, 46(11): 2867–2884. doi: 10.1007/s11064-021-03366-2
[53]	Correale J, Gaitán MI, Ysrraelit MC, et al. Progressive multiple sclerosis: from pathogenic mechanisms to treatment[J]. Brain, 2017, 140(3): 527–546. doi: 10.1093/brain/aww258
[54]	Reich DS, Lucchinetti CF, Calabresi A. Multiple sclerosis[J]. N Engl J Med, 2018, 378(2): 169–180. doi: 10.1056/NEJMra1401483
[55]	Haider L, Fischer MT, Frischer JM, et al. Oxidative damage in multiple sclerosis lesions[J]. Brain, 2011, 134(Pt 7): 1914–1924. doi: 10.1093/brain/awr128
[56]	Höftberger R, Fink S, Aboul-Enein F, et al. Tubulin polymerization promoting protein (TPPP/p25) as a marker for oligodendroglial changes in multiple sclerosis[J]. Glia, 2010, 58(15): 1847–1857. doi: 10.1002/glia.21054
[57]	Hollensworth SB, Shen CC, Sim JE, et al. Glial cell type-specific responses to menadione-induced oxidative stress[J]. Free Radic Biol Med, 2000, 28(8): 1161–1174. doi: 10.1016/S0891-5849(00)00214-8
[58]	Xu S, Lu J, Shao A, et al. Glial cells: role of the immune response in ischemic stroke[J]. Front Immunol, 2020, 11: 294. doi: 10.3389/fimmu.2020.00294
[59]	Lim JL, Van Der pol SMA, Baron W, et al. Protandim protects oligodendrocytes against an oxidative insult[J]. Antioxidants (Basel), 2016, 5(3): 30. doi: 10.3390/antiox5030030
[60]	Jana M, Pahan K. Redox regulation of cytokine-mediated inhibition of myelin gene expression in human primary oligodendrocytes[J]. Free Radic Biol Med, 2005, 39(6): 823–831. doi: 10.1016/j.freeradbiomed.2005.05.014
[61]	Deng Y, Xie D, Fang M, et al. Astrocyte-derived proinflammatory cytokines induce hypomyelination in the periventricular white matter in the hypoxic neonatal brain[J]. PLoS One, 2014, 9(1): e87420. doi: 10.1371/journal.pone.0087420
[62]	Kirby L, Jin J, Cardona JG, et al. Oligodendrocyte precursor cells present antigen and are cytotoxic targets in inflammatory demyelination[J]. Nat Commun, 2019, 10(1): 3887. doi: 10.1038/s41467-019-11638-3
[63]	Liu YJ, Aguzzi A. NG2 glia are required for maintaining microglia homeostatic state[J]. Glia, 2020, 68(2): 345–355. doi: 10.1002/glia.23721
[64]	Zhang SZ, Wang Q, Yang Q, et al. NG2 glia regulate brain innate immunity via TGF-β2/TGFBR2 axis[J]. BMC Med, 2019, 17(1): 204. doi: 10.1186/s12916-019-1439-x
[65]	McCauley ME, Baloh RH. Inflammation in ALS/FTD pathogenesis[J]. Acta Neuropathol, 2019, 137(5): 715–730. doi: 10.1007/s00401-018-1933-9
[66]	Beers DR, Appel SH. Immune dysregulation in amyotrophic lateral sclerosis: mechanisms and emerging therapies[J]. Lancet Neurol, 2019, 18(2): 211–220. doi: 10.1016/S1474-4422(18)30394-6
[67]	McCombe A, Lee JD, Woodruff TM, et al. The peripheral immune system and amyotrophic lateral sclerosis[J]. Front Neurol, 2020, 11: 279. doi: 10.3389/fneur.2020.00279
[68]	Cunha MI, Su M, Cantuti-Castelvetri L, et al. Pro-inflammatory activation following demyelination is required for myelin clearance and oligodendrogenesis[J]. J Exp Med, 2020, 217(5): e20191390. doi: 10.1084/jem.20191390