Select Neurotrophins Promote Oligodendrocyte Progenitor Cell Process Outgrowth in the Presence of Chondroitin Sulfate Proteoglycans

Overview

Journal J Neurosci Res

Specialty Neurology

Date 2021 Jan 16

PMID 33453083

Citations 13

Authors

Justin R Siebert

Donna J Osterhout

Affiliations

Soon will be listed here.

Abstract

Axonal damage and the subsequent interruption of intact neuronal pathways in the spinal cord are largely responsible for the loss of motor function after injury. Further exacerbating this loss is the demyelination of neighboring uninjured axons. The post-injury environment is hostile to repair, with inflammation, a high expression of chondroitin sulfate proteoglycans (CSPGs) around the glial scar, and myelin breakdown. Numerous studies have demonstrated that treatment with the enzyme chondroitinase ABC (cABC) creates a permissive environment around a spinal lesion that permits axonal regeneration. Neurotrophic factors like brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophic factor-3 (NT-3), and ciliary neurotrophic factor (CNTF) have been used to promote neuronal survival and stimulate axonal growth. CSPGs expressed near a lesion also inhibit migration and differentiation of endogenous oligodendrocyte progenitor cells (OPCs) in the spinal cord, and cABC treatment can neutralize this inhibition. This study examined the neurotrophins commonly used to stimulate axonal regeneration after injury and their potential effects on OPCs cultured in the presence of CSPGs. The results reveal differential effects on OPCs, with BDNF and GDNF promoting process outgrowth and NT-3 stimulating differentiation of OPCs, while CNTF appears to have no observable effect. This finding suggests that certain neurotrophic agents commonly utilized to stimulate axonal regeneration after a spinal injury may also have a beneficial effect on the endogenous oligodendroglial cells as well.

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References

DePaul M, Lin C, Silver J, Lee Y . Combinatory repair strategy to promote axon regeneration and functional recovery after chronic spinal cord injury. Sci Rep. 2017; 7(1):9018. PMC: 5567101. DOI: 10.1038/s41598-017-09432-6. View

Hashimoto M, Nitta A, Fukumitsu H, Nomoto H, Shen L, Furukawa S . Inflammation-induced GDNF improves locomotor function after spinal cord injury. Neuroreport. 2005; 16(2):99-102. DOI: 10.1097/00001756-200502080-00004. View

Siebert J, Conta Steencken A, Osterhout D . Chondroitin sulfate proteoglycans in the nervous system: inhibitors to repair. Biomed Res Int. 2014; 2014:845323. PMC: 4182688. DOI: 10.1155/2014/845323. View

Osterhout D, Ebner S, Xu J, Ornitz D, Zazanis G, McKinnon R . Transplanted oligodendrocyte progenitor cells expressing a dominant-negative FGF receptor transgene fail to migrate in vivo. J Neurosci. 1997; 17(23):9122-32. PMC: 6573602. View

Blesch A, Tuszynski M . Cellular GDNF delivery promotes growth of motor and dorsal column sensory axons after partial and complete spinal cord transections and induces remyelination. J Comp Neurol. 2003; 467(3):403-17. DOI: 10.1002/cne.10934. View

Monnier P, Sierra A, Schwab J, Henke-Fahle S, Mueller B . The Rho/ROCK pathway mediates neurite growth-inhibitory activity associated with the chondroitin sulfate proteoglycans of the CNS glial scar. Mol Cell Neurosci. 2003; 22(3):319-30. DOI: 10.1016/s1044-7431(02)00035-0. View

Cregg J, DePaul M, Filous A, Lang B, Tran A, Silver J . Functional regeneration beyond the glial scar. Exp Neurol. 2014; 253:197-207. PMC: 3951813. DOI: 10.1016/j.expneurol.2013.12.024. View

Li G, Che M, Zhang K, Qin L, Zhang Y, Chen R . Graft of the NT-3 persistent delivery gelatin sponge scaffold promotes axon regeneration, attenuates inflammation, and induces cell migration in rat and canine with spinal cord injury. Biomaterials. 2016; 83:233-48. DOI: 10.1016/j.biomaterials.2015.11.059. View

Yan H, WOOD P . NT-3 weakly stimulates proliferation of adult rat O1(-)O4(+) oligodendrocyte-lineage cells and increases oligodendrocyte myelination in vitro. J Neurosci Res. 2000; 62(3):329-35. DOI: 10.1002/1097-4547(20001101)62:3<329::AID-JNR2>3.0.CO;2-C. View

10.

Harlow D, Macklin W . Inhibitors of myelination: ECM changes, CSPGs and PTPs. Exp Neurol. 2013; 251:39-46. PMC: 4060786. DOI: 10.1016/j.expneurol.2013.10.017. View

11.

Griffin J, Bradke F . Therapeutic repair for spinal cord injury: combinatory approaches to address a multifaceted problem. EMBO Mol Med. 2020; 12(3):e11505. PMC: 7059014. DOI: 10.15252/emmm.201911505. View

12.

Du Y, Lercher L, Zhou R, Dreyfus C . Mitogen-activated protein kinase pathway mediates effects of brain-derived neurotrophic factor on differentiation of basal forebrain oligodendrocytes. J Neurosci Res. 2006; 84(8):1692-702. DOI: 10.1002/jnr.21080. View

13.

Ye J, Houle J . Treatment of the chronically injured spinal cord with neurotrophic factors can promote axonal regeneration from supraspinal neurons. Exp Neurol. 1997; 143(1):70-81. DOI: 10.1006/exnr.1996.6353. View

14.

Osterhout D, WOLVEN A, Wolf R, Resh M, Chao M . Morphological differentiation of oligodendrocytes requires activation of Fyn tyrosine kinase. J Cell Biol. 1999; 145(6):1209-18. PMC: 2133143. DOI: 10.1083/jcb.145.6.1209. View

15.

Siebert J, Eade A, Osterhout D . Biomaterial Approaches to Enhancing Neurorestoration after Spinal Cord Injury: Strategies for Overcoming Inherent Biological Obstacles. Biomed Res Int. 2015; 2015:752572. PMC: 4600545. DOI: 10.1155/2015/752572. View

16.

Ye J, Cao L, Cui R, Huang A, Yan Z, Lu C . The effects of ciliary neurotrophic factor on neurological function and glial activity following contusive spinal cord injury in the rats. Brain Res. 2004; 997(1):30-9. DOI: 10.1016/j.brainres.2003.10.036. View

17.

Gransee H, Zhan W, Sieck G, Mantilla C . Localized delivery of brain-derived neurotrophic factor-expressing mesenchymal stem cells enhances functional recovery following cervical spinal cord injury. J Neurotrauma. 2014; 32(3):185-93. PMC: 4298751. DOI: 10.1089/neu.2014.3464. View

18.

Vant Veer A, Du Y, Fischer T, Boetig D, Wood M, Dreyfus C . Brain-derived neurotrophic factor effects on oligodendrocyte progenitors of the basal forebrain are mediated through trkB and the MAP kinase pathway. J Neurosci Res. 2008; 87(1):69-78. PMC: 4912000. DOI: 10.1002/jnr.21841. View

19.

Iannotti C, Li H, Yan P, Lu X, Wirthlin L, Xu X . Glial cell line-derived neurotrophic factor-enriched bridging transplants promote propriospinal axonal regeneration and enhance myelination after spinal cord injury. Exp Neurol. 2003; 183(2):379-93. DOI: 10.1016/s0014-4886(03)00188-2. View

20.

Heinrich M, Gorath M, Richter-Landsberg C . Neurotrophin-3 (NT-3) modulates early differentiation of oligodendrocytes in rat brain cortical cultures. Glia. 1999; 28(3):244-55. View