Entrapment via synaptic-like connections between NG2 proteoglycan + cells and dystrophic axons in the lesion plays a role in regeneration failure after spinal cord injury

Journal of Neuroscience

Volumn 34, Issue 49, 2014, Pages 16369-16384

  Filous, Angela R ^a   Tran, Amanda ^a   James Howell, C ^a   Busch, Sarah A ^a   Evans, Teresa A ^a   Stallcup, William B ^b   Kang, Shin H ^c   Bergles, Dwight E ^c   Lee, Seong Il ^d   Levine, Joel M ^d   Silver, Jerry ^a  

^a CASE WESTERN RESERVE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b BURNHAM INSTITUTE   (United States)

^c JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d STONY BROOK UNIVERSITY   (United States)

Author keywords

Chondroitinase; Dystrophic axons; Glial scar; NG2 proteoglycan; Oligodendrocyte progenitor cells; Spinal cord injury

Indexed keywords

BETA1 INTEGRIN; CELL ADHESION MOLECULE; CHONDROITIN ABC LYASE; ECTODYSPLASIN A; FIBRONECTIN; GLIAL FIBRILLARY ACIDIC PROTEIN; LAMININ; PROTEOCHONDROITIN SULFATE; PROTEOGLYCAN; SYNAPTOSOMAL ASSOCIATED PROTEIN 25; VIMENTIN; ANTIGEN; CHONDROITIN SULFATE PROTEOGLYCAN 4;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN CELL CULTURE; BRAIN DAMAGE; CELL ASSAY; CELL COUNT; CELL INTERACTION; CELL LABELING; CONTROLLED STUDY; GENE INACTIVATION; IMMUNOCYTOCHEMISTRY; IMMUNOHISTOCHEMISTRY; MOUSE; NERVE COMPRESSION; NERVE FIBER GROWTH; NERVE FIBER MEMBRANE POTENTIAL; NERVE FIBER REGENERATION; NEUROAXONAL DYSTROPHY; NONHUMAN; OLIGODENDROCYTE PRECURSOR CELL; PROTEIN EXPRESSION; RECEPTOR UPREGULATION; SENSORY NERVE CELL; SPINAL CORD DORSAL HORN; SPINAL CORD INJURY; SPINAL GANGLION; STRIPE ASSAY; SYNAPTIC POTENTIAL; SYNAPTIC VESICLE CYCLING ASSAY; TRANSMISSION ELECTRON MICROSCOPY; WESTERN BLOTTING; ANIMAL; CELL COMMUNICATION; CELL CULTURE; CELL TRACKING; GENETICS; KNOCKOUT MOUSE; NERVE DEGENERATION; NERVE FIBER; NERVE REGENERATION; PATHOPHYSIOLOGY; PHYSIOLOGY; SYNAPSE; ULTRASTRUCTURE;

ANIMALS; ANTIGENS; ANTIGENS, CD29; AXONS; CELL COMMUNICATION; CELL TRACKING; CELLS, CULTURED; CHONDROITIN SULFATE PROTEOGLYCANS; FIBRONECTINS; GANGLIA, SPINAL; LAMININ; MICE; MICE, KNOCKOUT; NERVE DEGENERATION; NERVE REGENERATION; PROTEOGLYCANS; SPINAL CORD INJURIES; SYNAPSES;

EID: 84914679498     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.1309-14.2014     Document Type: Article

References (64)

1. Asher RA, Morgenstern DA, Shearer MC, Adcock KH, Pesheva P, Fawcett JW (2002) Versican is upregulated in CNS injury and is a product of oligodendrocyte lineage cells. J Neurosci 22:2225-2236.Medline
2. Bai L, Hecker J, Kerstetter A, Miller RH (2013) Myelin repair and functional recovery mediated by neural cell transplantation in a mouse model of multiple sclerosis. Neurosci Bull 29:239-250. CrossRef Medline
3. Bergles DE, Roberts JD, Somogyi P, Jahr CE (2000) Glutamatergic synapses on oligodendrocyte precursor cells in the hippocampus. Nature 405:187-191. CrossRef Medline
4. Bradbury EJ, Moon LD, Popat RJ, King VR, Bennett GS, Patel PN, Fawcett JW, McMahon SB (2002) Chondroitinase ABC promotes functional recovery after spinal cord injury. Nature 416:636-640. CrossRef Medline
5. Burden-Gulley SM, Payne HR, Lemmon V (1995) Growth cones are actively influenced by substrate-bound adhesion molecules. J Neurosci 15: 4370-4381.Medline
6. Busch SA, Horn KP, Cuascut FX, Hawthorne AL, Bai L, Miller RH, Silver J (2010) Adult NG2_cells are permissive to neurite outgrowth and stabilize sensory axons during macrophage-induced axonal dieback after spinal cord injury. J Neurosci 30:255-265. CrossRef Medline
7. Carlstedt T (1985) Regenerating axons form nerve terminals at astrocytes. Brain Res 347:188-191. CrossRef Medline
8. Challacombe JF, Snow DM, Letourneau PC (1996) Actin filament bundles are required for microtubule reorientation during growth cone turning to avoid an inhibitory guidance cue. J Cell Sci 109:2031-2040. Medline
9. Challacombe JF, Snow DM, Letourneau PC (1997) Dynamic microtubule ends are required for growth cone turning to avoid an inhibitory guidance cue. J Neurosci 17:3085-3095.Medline
10. Chekenya M, Krakstad C, Svendsen A, Netland IA, Staalesen V, Tysnes BB, Selheim F, Wang J, Sakariassen PØ, Sandal T, Lønning PE, Flatmark T, Enger PØ, Bjerkvig R, Sioud M, Stallcup WB (2008) The progenitor cell marker NG2/MPG promotes chemoresistance by activation of integrin-dependent PI3K/Akt signaling. Oncogene 27:5182-5194. CrossRef Medline
11. Condic ML, Snow DM, Letourneau PC (1999) Embryonic neurons adapt to the inhibitory proteoglycan aggrecan by increasing integrin expression. J Neurosci 19:10036-10043. Medline
12. de Castro R Jr, Tajrishi R, Claros J, Stallcup WB (2005) Differential responses of spinal axons to transection: influence of theNG2proteoglycan. Exp Neurol 192:299-309. CrossRef Medline
13. Di Maio A, Skuba A, Himes BT, Bhagat SL, Hyun JK, Tessler A, Bishop D, Son YJ (2011) In vivo imaging of dorsal root regeneration: rapid immobilization and presynaptic differentiation at the CNS/PNS border. J Neurosci 31:4569-4582. CrossRef Medline
14. Dou CL, Levine JM (1994) Inhibition of neurite growth by the NG2 chondroitin sulfate proteoglycan. J Neurosci 14:7616-7628.Medline
15. Fidler PS, Schuette K, Asher RA, Dobbertin A, Thornton SR, Calle-Patino Y, Muir E, Levine JM, Geller HM, Rogers JH, Faissner A, Fawcett JW (1999) Comparing astrocytic cell lines that are inhibitory or permissive for axon growth: the major axon-inhibitory proteoglycan is NG2. J Neurosci 19: 8778-8788.Medline
16. Fisher D, Xing B, Dill J, Li H, Hoang HH, Zhao Z, Yang XL, Bachoo R, Cannon S, Longo FM, Sheng M, Silver J, Li S (2011) Leukocyte common antigen-related phosphatase is a functional receptor for chondroitin sulfate proteoglycan axon growth inhibitors. J Neurosci 31:14051-14066. CrossRef Medline
17. Fitch MT, Silver J (1997) Glial cell extracellular matrix: boundaries for axon growth in development and regeneration. Cell Tissue Res 290:379-384. CrossRef Medline
18. Frisén J, Haegerstrand A, Risling M, Fried K, Johansson CB, Hammarberg H, Elde R, Hökfelt T, Cullheim S (1995) Spinal axons in central nervous system scar tissue are closely related to laminin-immunoreactive astrocytes. Neuroscience 65:293-304. CrossRef Medline
19. Fukushi J, Makagiansar IT, Stallcup WB (2004) NG2 proteoglycan promotes endothelial cell motility and angiogenesis via engagement of galectin-3 and alpha3beta1 integrin. Mol Biol Cell 15:3580-3590. CrossRef Medline
20. Gallo V, Mangin JM, Kukley M, Dietrich D (2008) Synapses on NG2-expressing progenitors in the brain: multiple functions? J Physiol 586: 3767-3781. CrossRef Medline
21. Göritz C, Dias DO, Tomilin N, Barbacid M, Shupliakov O, Frisén J (2011) A pericyte origin of spinal cord scar tissue. Science 333:238-242. CrossRef Medline
22. Grimpe B, Pressman Y, Lupa MD, Horn KP, Bunge MB, Silver J (2005) The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces. Mol Cell Neurosci 28:18-29. CrossRef Medline
23. Hanaichi T, Sato T, Iwamoto T, Malavasi-Yamashiro J, Hoshino M, Mizuno N (1986) A stable lead by modification of Sato’s method. J Electron Microsc 35:304-306.Medline
24. Horn KP, Busch SA, Hawthorne AL, van Rooijen N, Silver J (2008) Another barrier to regeneration in the CNS: activated macrophages induce extensive retraction of dystrophic axons through direct physical interactions. J Neurosci 28:9330-9341. CrossRef Medline
25. Houle JD (1991) Demonstration of the potential for chronically injured neurons to regenerate axons into intraspinal peripheral nerve grafts. Exp Neurol 113:1-9. CrossRef Medline
26. Ippolito DM, Eroglu C (2010) Quantifying synapses: an immunocytochemistrybased assay to quantify synapse number. J Vis Exp 45:2270. CrossRef Medline
27. Jones LL, Yamaguchi Y, Stallcup WB, Tuszynski MH (2002) NG2 is a major chondroitin sulfate proteoglycan produced after spinal cord injury and is expressed by macrophages and oligodendrocyte progenitors. J Neurosci 22:2792-2803.Medline
28. Jones LL, Sajed D, Tuszynski MH (2003) Axonal regeneration through regions of chondroitin sulfate proteoglycan deposition after spinal cord injury: a balance of permissiveness and inhibition. J Neurosci 23:9276-9288.Medline
29. Karnovsky MJ (1971) Use of ferrocyanide-reduced osmium tetroxide in electron microscopy. Proceedings of the 11th Annual Meeting of the American Society of Cell Biology, p 146. New Orleans.
30. Kiani C, Chen L, Wu YJ, Yee AJ, Yang BB (2002) Structure and function of aggrecan. Cell Res 12:19-32. CrossRef Medline
31. Knöll B, Weinl C, Nordheim A, Bonhoeffer F (2007) Stripe assay toexamineaxonal guidance and cell migration. Nat Protoc 2:1216-1224. CrossRef Medline
32. Kuffler DP1, Sosa IJ, Reyes O (2009) Schwann cell chondroitin sulfate proteoglycan inhibits dorsal root ganglion neuron neurite outgrowth and substrate specificity via a soma and not a growth cone mechanism. J Neurosci Res 87:28663-28671. CrossRef Medline
33. Kukley M, Capetillo-Zarate E, Dietrich D (2007) Vesicular glutamate release from axons in white matter. Nat Neurosci 10:311-320. CrossRef Medline
34. Kwon BK, Liu J, Messerer C, Kobayashi NR, McGraw J, Oschipok L, Tetzlaff W (2002) Survival and regeneration of rubrospinal neurons 1 year after spinal cord injury. Proc Natl Acad Sci U S A 99:3246-3251. CrossRef Medline
35. Levine JM (1994) Increased expression of the NG2 chondroitin-sulfate proteoglycan after brain injury. J Neurosci 14:4716-4730.Medline
36. Lewandowski G, Steward O (2014) AAVshRNA-mediated suppression of PTEN in adult rats in combination with salmon fibrin administration enables regenerative growth of corticospinal axons and enhances recovery of voluntary motor function after cervical spinal cord injury. J Neurosci 34:9951-9962. CrossRef Medline
37. Liuzzi FJ, Lasek RJ (1987) Astrocytes block axonal regeneration in mammals by activating the physiological stop pathway. Science 237:642-645. CrossRef Medline
38. Lu P, Jones LL, Tuszynski MH (2007) Axon regeneration through scars and into sites of chronic spinal cord injury. Exp Neurol 203:8-21. CrossRef Medline
39. Lytle JM, Vicini S, Wrathall JR (2006) Phenotypic changes in NG2_cells after spinal cord injury. J Neurotrauma 23:1726-1738. CrossRef Medline
40. Makagiansar IT, Williams S, Mustelin T, Stallcup WB (2007) Differential phosphorylation of NG2 proteoglycan by ERK and PKCalpha helps balance cell proliferation and migration. J Cell Biol 178:155-165. CrossRef Medline
41. McKeon RJ, Schreiber RC, Rudge JS, Silver J (1991) Reduction of neurite outgrowth in a model of glial scarring following CNS injury is correlated with the expression of inhibitory molecules on reactive astrocytes. J Neurosci 11:3398-3411.Medline
42. McQuarrie IG, Grafstein B (1973) Axon outgrowth enhanced by a previous nerve injury. Arch Neurol 29:53-55. CrossRef Medline
43. McQuarrie IG, Grafstein B, Gershon MD (1977) Axonal regeneration in the rat sciatic nerve: effect of a conditioning lesion and of dbcAMP. Brain Res 132:443-453. CrossRef Medline
44. McTigue DM, Wei P, Stokes BT (2001) Proliferation of NG2-positive cells and altered oligodendrocyte numbers in the contused rat spinal cord. J Neurosci 21:3392-3400.Medline
45. McTigue DM, Tripathi R, Wei P (2006) NG2 colocalizes with axons and is expressed by a mixed cell population in spinal cord lesions. J Neuropathol Exp Neurol 65:406-420. CrossRef Medline
46. Neumann S, Skinner K, Basbaum AI (2005) Sustaining intrinsic growth capacity of adult neurons promotes spinal cord regeneration. Proc Natl Acad Sci U S A 102:16848-16852. CrossRef Medline
47. Nielson JL, Sears-Kraxberger I, Strong MK, Wong JK, Willenberg R, Steward O (2010) Unexpected survival of neurons of origin of the pyramidal tract after spinal cord injury. J Neurosci 30:11516-11528. CrossRef Medline
48. Ramon y Cajal S (1928) Degeneration and regeneration of the nervous system. London: Oxford UP.
49. Richardson PM, Issa VM (1984) Peripheral injury enhances central regeneration of primary sensory neurones. Nature 309:791-793. CrossRef Medline
50. Shen Y, Tenney AP, Busch SA, Horn KP, Cuascut FX, Liu K, He Z, Silver J, Flanagan JG (2009) PTPsigma is a receptor for chondroitin sulfate proteoglycan, an inhibitor of neural regeneration. Science 326:592-596. CrossRef Medline
51. Snow DM, Lemmon V, Carrino DA, Caplan AI, Silver J (1990) Sulfated proteoglycans in astroglial barriers inhibit neurite outgrowth in vitro. Exp Neurol 109:111-130. CrossRef Medline
52. Soderblom C, Luo X, Blumenthal E, Bray E, Lyapichev K, Ramos J, Krishnan V, Lai-Hsu C, Park KK, Tsoulfas P, Lee JK (2013) Perivascular fibroblasts form the fibrotic scar after contusive spinal cord injury. J Neurosci 33:13882-13887. CrossRef Medline
53. Stallcup WB, Dahlin-Huppe K (2001) Chondroitin sulfate and cytoplasmic domain-dependent membrane targeting of the NG2 proteoglycan promotes retraction fiber formation and cell polarization. J Cell Sci 114: 2315-2325.Medline
54. Sumner BE (1975) A quantitative study of subsurface cisterns and their relationships in normal and axotomized hypoglossal neurones. Exp Brain Res 22:175-183.Medline
55. Sun F, Park KK, Belin S, Wang D, Lu T, Chen G, Zhang K, Yeung C, Feng G, Yankner BA, He Z (2011) Sustained axon regeneration induced by codeletion of PTEN and SOCS3. Nature 480:372-375. CrossRef Medline
56. Tan AM, Zhang W, Levine JM (2005) NG2: a component of the glial scar that inhibits axon growth. J Anat 207:717-725. CrossRef Medline
57. Tandler B (1990) Improved uranyl acetate staining for electron microscopy. J Electron Microsc Tech 16:81-82. CrossRef Medline
58. Tomaselli KJ, Doherty P, Emmett CJ, Damsky CH, Walsh FS, Reichardt LF (1993) Expression of beta 1 integrins in sensory neurons of the dorsal root ganglion and their functions in neurite outgrowth on two laminin isoforms. J Neurosci 13:4880-4888.Medline
59. Tom VJ, Doller CM, Malouf AT, Silver J (2004a) Astrocyte-associated fibronectin is critical for axonal regeneration in adult white matter. J Neurosci 24:9282-9290. CrossRef Medline
60. Tom VJ, Steinmetz MP, Miller JH, Doller CM, Silver J (2004b) Studies on the development and behavior of the dystrophic growth cone, the hallmark of regeneration failure, in an in vitro model of the glial scar and after spinal cord injury. J Neurosci 24:6531-6539. CrossRef Medline
61. Ughrin YM, Chen ZJ, Levine JM (2003) Multiple regions of the NG2 proteoglycan inhibit neurite growth and induce growth cone collapse. J Neurosci 23:175-186.Medline
62. Um JW, Ko J (2013) LAR-RPTPs: synaptic adhesion molecules that shape synapse development. Trends Cell Biol 23:465-475. CrossRef Medline
63. Yang Z, Suzuki R, Daniels SB, Brunquell CB, Sala CJ, Nishiyama A (2006) NG2 glial cells provide a favorable substrate for growing axons. J Neurosci 26:3829-3839. CrossRef Medline
64. Zai LJ, Wrathall JR (2005) Cell proliferation and replacement following contusive spinal cord injury. Glia 50:247-257. CrossRef Medline