Overexpression of the astrocyte glutamate transporter GLT1 exacerbates phrenic motor neuron degeneration, diaphragm compromise, and forelimb motor dysfunction following cervical contusion spinal cord injury

Journal of Neuroscience

Volumn 34, Issue 22, 2014, Pages 7622-7638

  Li, Ke ^a   Nicaise, Charles ^a,b   Sannie, Daniel ^a   Hala, Tamara J ^a   Javed, Elham ^a   Parker, Jessica L ^a   Putatunda, Rajarshi ^a   Regan, Kathleen A ^a   Suain, Valérie ^c   Brion, Jean Pierre ^c   Rhoderick, Fred ^d   Wright, Megan C ^e   Poulsen, David J ^d   Lepore, Angelo C ^a  

^a THOMAS JEFFERSON UNIVERSITY   (United States)

^b University of Namur   (Belgium)

^c UNIVERSITÉ LIBRE DE BRUXELLES   (Belgium)

^d UNIVERSITY OF MONTANA   (United States)

^e ARCADIA UNIVERSITY   (United States)

Author keywords

Adeno associated virus; Gene therapy; Glutamate transporter; Phrenic motor neuron; Respiratory; Spinal cord injury

Indexed keywords

ADENO ASSOCIATED VIRUS TYPE 8 VECTOR; GLUTAMATE TRANSPORTER; PARVOVIRUS VECTOR; UNCLASSIFIED DRUG; VESICULAR GLUTAMATE TRANSPORTER 1;

ANIMAL TISSUE; ARTICLE; ASTROCYTE; CELL DEATH; CELL PROLIFERATION; CERVICAL SPINAL CORD INJURY; CONTROLLED STUDY; CYLINDER PAW PREFERENCE TEST; DENERVATION; DIAPHRAGM; ELECTROPHYSIOLOGY; EXPERIMENTAL BEHAVIORAL TEST; FEMALE; FORELIMB; GENE TARGETING; GENE THERAPY; GENETIC TRANSDUCTION; GRIP STRENGTH TEST; HISTOLOGY; IMMUNOBLOTTING; IMMUNOHISTOCHEMISTRY; MALE; MOTOR DYSFUNCTION; MOTOR NEURON DEGENERATION; MOUSE; NERVE DEGENERATION; NERVE INJURY; NEUROMUSCULAR SYNAPSE; NONHUMAN; PHRENIC NERVE; PRIORITY JOURNAL; PROTEIN EXPRESSION; RAT; TRANSGENIC MOUSE;

ADENO-ASSOCIATED VIRUS; GENE THERAPY; GLUTAMATE TRANSPORTER; PHRENIC MOTOR NEURON; RESPIRATORY; SPINAL CORD INJURY;

ANIMALS; ASTROCYTES; CERVICAL VERTEBRAE; DIAPHRAGM; EXCITATORY AMINO ACID TRANSPORTER 2; FEMALE; FORELIMB; GENE EXPRESSION REGULATION; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; MOTOR NEURONS; NERVE DEGENERATION; PHRENIC NERVE; RATS; RATS, SPRAGUE-DAWLEY; SPINAL CORD INJURIES;

EID: 84901436063     PISSN: 02706474     EISSN: 15292401     Source Type: Journal    
DOI: 10.1523/JNEUROSCI.4690-13.2014     Document Type: Article

References (78)

1. Agrawal SK, Fehlings MG (1997) Role of NMDA and non-NMDA ionotropic glutamate receptors in traumatic spinal cord axonal injury. J Neurosci 17:1055-1063. Medline
2. Bal-Price A, Brown GC (2001) Inflammatory neurodegeneration mediated by nitric oxide from activated glia-inhibiting neuronal respiration, causing glutamate release and excitotoxicity. J Neurosci 21:6480-6491. Medline
3. Bleakman D, Alt A, Nisenbaum ES (2006) Glutamate receptors and pain. Semin Cell Dev Biol 17:592-604. CrossRef Medline
4. Brown AM, Ransom BR (2007) Astrocyte glycogen and brain energy metabolism. Glia 55:1263-1271. CrossRef Medline
5. Carlson GD, Gorden C (2002) Current developments in spinal cord injury research. Spine J 2:116-128. CrossRef Medline
6. Cataldo AM, Broadwell RD (1986) Cytochemical identification of cerebral glycogen and glucose-6-phosphatase activity under normal and experimental conditions. II. Choroid plexus and ependymal epithelia, endothelia and pericytes. J Neurocytol 15:511-524. CrossRef Medline
7. Choi DW, Rothman SM (1990) The role of glutamate neurotoxicity in hypoxic-ischemic neuronal death. Annu Rev Neurosci 13:171-182. CrossRef Medline
8. Colleoni S, Jensen AA, Landucci E, Fumagalli E, Conti P, Pinto A, De Amici M, Pellegrini-Giampietro DE, De Micheli C, Mennini T, GobbiM (2008) Neuroprotective effects of the novel glutamate transporter inhibitor (-)-3-hydroxy-4,5,6,6a-tetrahydro-3aH-pyrrolo[3,4-d]-isoxazole-4-carboxylic acid, which preferentially inhibits reverse transport (glutamate release) compared with glutamate reuptake. J Pharmacol Exp Ther 326:646-656. CrossRef Medline
9. Davies JE, Pröschel C, Zhang N, Noble M, Mayer-Pröschel M, Davies SJ (2008) Transplanted astrocytes derived from BMP-or CNTF-treated glial-restricted precursors have opposite effects on recovery and allodynia after spinal cord injury. J Biol 7:24. CrossRef Medline
10. Dowd LA, Robinson MB (1996) Rapid stimulation of EAAC1-mediated Na+-dependent L-glutamate transport activity in C6 glioma cells by phorbol ester. J Neurochem 67:508-516. Medline
11. D'Souza SD, Alinauskas KA, Antel JP (1996) Ciliary neurotrophic factor selectively protects human oligodendrocytes from tumor necrosis factormediated injury. J Neurosci Res 43:289-298. CrossRef Medline
12. Faulkner JR, Herrmann JE, Woo MJ, Tansey KE, Doan NB, Sofroniew MV (2004) Reactive astrocytes protect tissue and preserve function after spinal cord injury. J Neurosci 24:2143-2155. CrossRef Medline
13. Gaviria M, Privat A, d'Arbigny P, Kamenka J, Haton H, Ohanna F (2000) Neuroprotective effects of a novel NMDA antagonist, gacyclidine, after experimental contusive spinal cord injury in adult rats. Brain Res 874: 200-209. CrossRef Medline
14. Goldberg MP, ChoiDW (1993) Combined oxygen and glucose deprivation in cortical cell culture: calcium-dependent and calcium-independent mechanisms of neuronal injury. J Neurosci 13:3510-3524. Medline
15. Gouix E, Léveillé F, Nicole O, Melon C, Had-Aissouni L, Buisson A (2009) Reverse glial glutamate uptake triggers neuronal cell death through extrasynaptic NMDA receptor activation. Mol Cell Neurosci 40:463-473. CrossRef Medline
16. Grewer C, Gameiro A, Zhang Z, Tao Z, Braams S, Rauen T (2008) Glutamate forward and reverse transport: from molecular mechanism to transporter-mediated release after ischemia. IUBMB Life 60:609-619. CrossRef Medline
17. Gwak YS, Hulsebosch CE (2011) Neuronal hyperexcitability: a substrate for central neuropathic pain after spinal cord injury. Curr Pain Headache Rep 15:215-222. CrossRef Medline
18. Gwak YS, Kang J, Unabia GC, Hulsebosch CE (2012) Spatial and temporal activation of spinal glial cells: role of gliopathy in central neuropathic pain following spinal cord injury in rats. Exp Neurol 234:362-372. CrossRef Medline
19. Harvey BK, Airavaara M, Hinzman J, Wires EM, Chiocco MJ, Howard DB, Shen H, Gerhardt G, Hoffer BJ, Wang Y (2011) Targeted overexpression of glutamate transporter 1 (GLT-1) reduces ischemic brain injury in a rat model of stroke. PLoS One 6:e22135. CrossRef Medline
20. Kawano H, Kimura-Kuroda J, Komuta Y, Yoshioka N, Li HP, Kawamura K, Li Y, RaismanG (2012) Role of the lesion scar in the response to damage and repair of the central nervous system. Cell Tissue Res 349:169-180. CrossRef Medline
21. Kim Y, Park YK, Cho HY, Kim J, Yoon YW (2011) Long-term changes in expressions of spinal glutamate transporters after spinal cord injury. Brain Res 1389:194-199. CrossRef Medline
22. Kosugi T, Kawahara K (2006) Reversed actrocytic GLT-1 during ischemia is crucial to excitotoxic death of neurons, but contributes to the survival of astrocytes themselves. Neurochem Res 31:933-943. CrossRef Medline
23. Lane MA, Fuller DD, White TE, Reier PJ (2008) Respiratory neuroplasticity and cervical spinal cord injury: translational perspectives. Trends Neurosci 31:538-547. CrossRef Medline
24. Laskowski MB, Sanes JR (1987) Topographic mapping of motor pools onto skeletal muscles. J Neurosci 7:252-260. Medline
25. Lepore AC (2011) Intraspinal cell transplantation for targeting cervical ventral horn in amyotrophic lateral sclerosis and traumatic spinal cord injury. J Vis Exp (55):pii:3069. CrossRef Medline
26. Lepore AC, Fischer I (2005) Lineage-restricted neural precursors survive, migrate, and differentiate following transplantation into the injured adult spinal cord. Exp Neurol 194:230-242. CrossRef Medline
27. Lepore AC, Maragakis NJ (2011) Stem cell transplantation for spinal cord neurodegeneration. Methods Mol Biol 793:479-493. CrossRef Medline
28. Lepore AC, Walczak P, Rao MS, Fischer I, Bulte JW (2006) MR imaging of lineage-restricted neural precursors following transplantation into the adult spinal cord. Exp Neurol 201:49-59. CrossRef Medline
29. Lepore AC, Dejea C, Carmen J, Rauck B, Kerr DA, Sofroniew MV, Maragakis NJ (2008a) Selective ablation of proliferating astrocytes does not affect disease outcome in either acute or chronic models of motor neuron degeneration. Exp Neurol 211:423-432. CrossRef Medline
30. Lepore AC, Rauck B, Dejea C, Pardo AC, Rao MS, Rothstein JD, Maragakis NJ (2008b) Focal transplantation-based astrocyte replacement is neuroprotective in a model of motor neuron disease. Nat Neurosci 11:1294-1301. CrossRef Medline
31. Lepore AC, Tolmie C, O'Donnell J, Wright MC, Dejea C, Rauck B, Hoke A, Ignagni AR, Onders RP, Maragakis NJ (2010) Peripheral hyperstimulation alters site of disease onset and course in SOD1 rats. Neurobiol Dis 39:252-264. CrossRef Medline
32. Lepore AC, O'Donnell J, Bonner JF, Paul C, Miller ME, Rauck B, Kushner RA, Rothstein JD, Fischer I, Maragakis NJ (2011a) Spatial and temporal changes in promoter activity of the astrocyte glutamate transporter GLT1 following traumatic spinal cord injury. J Neurosci Res 89:1001-1017. CrossRef Medline
33. Lepore AC, O'Donnell J, Kim AS, Williams T, Tuteja A, Rao MS, Kelley LL, Campanelli JT, Maragakis NJ (2011b) Human glial-restricted progenitor transplantation into cervical spinal cord of the SOD1 mouse model of ALS. PLoS One 6:e25968. CrossRef Medline
34. Lepore AC, O'Donnell J, Kim AS, Yang EJ, Tuteja A, Haidet-Phillips A, O'Banion CP, Maragakis NJ (2011c) Reduction in expression of the astrocyte glutamate transporter, GLT1, worsens functional and histological outcomes following traumatic spinal cord injury. Glia 59:1996-2005. CrossRef Medline
35. Leroy K, Bretteville A, Schindowski K, Gilissen E, Authelet M, De Decker R, Yilmaz Z, Buée L, Brion JP (2007) Early axonopathy preceding neurofibrillary tangles in mutant tau transgenic mice. Am J Pathol 171:976-992. CrossRef Medline
36. Liu D, Thangnipon W, McAdoo DJ (1991) Excitatory amino acids rise to toxic levels upon impact injury to the rat spinal cord. Brain Res 547:344-348. CrossRef Medline
37. Maeda S, Kawamoto A, Yatani Y, Shirakawa H, Nakagawa T, Kaneko S (2008) Gene transfer of GLT-1, a glial glutamate transporter, into the spinal cord by recombinant adenovirus attenuates inflammatory and neuropathic pain in rats. Mol Pain 4:65. CrossRef Medline
38. Mantilla CB, Zhan WZ, Sieck GC (2009) Retrograde labeling of phrenic motoneurons by intrapleural injection. J Neurosci Methods 182:244-249. CrossRef Medline
39. Maragakis NJ, Rothstein JD (2004) Glutamate transporters: animal models to neurologic disease. Neurobiol Dis 15:461-473. CrossRef Medline
40. Matute C, Alberdi E, Domercq M, Sánchez-Gómez MV, Pérez-Samartín A, Rodríguez-Antigüedad A, Pérez-Cerdá F (2007) Excitotoxic damage to white matter. J Anat 210:693-702. CrossRef Medline
41. McAdoo DJ, Xu GY, Robak G, Hughes MG (1999) Changes in amino acid concentrations over time and space around an impact injury and their diffusion through the rat spinal cord. Exp Neurol 159:538-544. CrossRef Medline
42. Min KJ, Jeong HK, Kim B, Hwang DH, Shin HY, Nguyen AT, Kim JH, Jou I, Kim BG, Joe EH (2012) Spatial and temporal correlation in progressive degeneration of neurons and astrocytes in contusion-induced spinal cord injury. J Neuroinflammation 9:100. CrossRef Medline
43. Mitani A, Tanaka K (2003) Functional changes of glial glutamate transporter GLT-1 during ischemia: an in vivo study in the hippocampal CA1 of normal mice and mutant mice lacking GLT-1. J Neurosci 23:7176-7182. Medline
44. Monahan PE, Jooss K, Sands MS (2002) Safety of adeno-associated virus gene therapy vectors: a current evaluation. Expert Opin Drug Saf 1:79-91. CrossRef Medline
45. Neumann H, Schweigreiter R, Yamashita T, Rosenkranz K, Wekerle H, Barde YA (2002) Tumor necrosis factor inhibits neurite outgrowth and branching of hippocampal neurons by a rho-dependent mechanism. J Neurosci 22:854-862. Medline
46. Nicaise C, Hala TJ, Frank DM, Parker JL, Authelet M, Leroy K, Brion JP, Wright MC, Lepore AC (2012a) Phrenic motor neuron degeneration compromises phrenic axonal circuitry and diaphragm activity in a unilateral cervical contusion model of spinal cord injury. Exp Neurol 235:539-552. CrossRef Medline
47. Nicaise C, Putatunda R, Hala TJ, Regan KA, Frank DM, Brion JP, Leroy K, Pochet R, Wright MC, Lepore AC (2012b) Degeneration of phrenic motor neurons induces long-term diaphragm deficits following mid-cervical spinal contusion in mice. J Neurotrauma 29:2748-2760. CrossRef Medline
48. Nicaise C, Frank DM, Hala TJ, Authelet M, Pochet R, Adriaens D, Brion JP, Wright MC, Lepore AC (2013) Early phrenic motor neuron loss and transient respiratory abnormalities after unilateral cervical spinal cord contusion. J Neurotrauma 30:1092-1099. CrossRef Medline
49. Nishio T, Kawaguchi S, Yamamoto M, Iseda T, Kawasaki T, Hase T (2005) Tenascin-C regulates proliferation and migration of cultured astrocytes in a scratch wound assay. Neuroscience 132:87-102. CrossRef Medline
50. Oh JW, Schwiebert LM, Benveniste EN (1999) Cytokine regulation of CC and CXC chemokine expression by human astrocytes. J Neurovirol 5:82-94. CrossRef Medline
51. Olsen ML, Campbell SC, McFerrin MB, Floyd CL, Sontheimer H (2010) Spinal cord injury causes a wide-spread, persistent loss of Kir4.1 and glutamate transporter 1: benefit of 17 beta-oestradiol treatment. Brain 133:1013-1025. CrossRef Medline
52. Oyinbo CA (2011) Secondary injury mechanisms in traumatic spinal cord injury: a nugget of this multiply cascade. Acta Neurobiol Exp (Wars) 71:281-299. Medline
53. Panter SS, YumSW, Faden AI (1990) Alteration in extracellular amino acids after traumatic spinal cord injury. Ann Neurol 27:96-99. CrossRef Medline
54. Park E, Velumian AA, Fehlings MG (2004) The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration. J Neurotrauma 21: 754-774. CrossRef Medline
55. Pekny M, Nilsson M (2005) Astrocyte activation and reactive gliosis. Glia 50:427-434. CrossRef Medline
56. Ponnazhagan S, Mukherjee P, Yoder MC, Wang XS, Zhou SZ, Kaplan J, Wadsworth S, Srivastava A (1997) Adeno-associated virus 2-mediated gene transfer in vivo: organ-tropism and expression of transduced sequences in mice. Gene 190:203-210. CrossRef Medline
57. Rao VL, Dogan A, Bowen KK, Todd KG, Dempsey RJ (2001) Antisense knockdown of the glial glutamate transporter GLT-1 exacerbates hippocampal neuronal damage following traumatic injury to rat brain. Eur J Neurosci 13:119-128. CrossRef Medline
58. Regan MR, Huang YH, Kim YS, Dykes-Hoberg MI, Jin L, Watkins AM, Bergles DE, Rothstein JD (2007) Variations in promoter activity reveal a differential expression and physiology of glutamate transporters by glia in the developing and mature CNS. J Neurosci 27:6607-6619. CrossRef Medline
59. Rosenberg LJ, Teng YD, Wrathall JR (1999) 2,3-Dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline reduces glial loss and acute white matter pathology after experimental spinal cord contusion. J Neurosci 19:464-475. Medline
60. Rossi DJ, Brady JD, Mohr C (2007) Astrocyte metabolism and signaling during brain ischemia. Nat Neurosci 10:1377-1386. CrossRef Medline
61. Shirasaki Y, Sugimura M, Sato T (2010) Bromocriptine, an ergot alkaloid, inhibits excitatory amino acid release mediated by glutamate transporter reversal. Eur J Pharmacol 643:48-57. CrossRef Medline
62. Sofroniew MV (2005) Reactive astrocytes in neural repair and protection. Neuroscientist 11:400-407. CrossRef Medline
63. Stewart VC, Heslegrave AJ, Brown GC, Clark JB, Heales SJ (2002) Nitric oxide-dependent damage to neuronal mitochondria involves the NMDA receptor. Eur J Neurosci 15:458-464. CrossRef Medline
64. Strakowski JA, Pease WS, Johnson EW (2007) Phrenic nerve stimulation in the evaluation of ventilator-dependent individuals with C4-and C5-level spinal cord injury. AmJ Phys Med Rehabil 86:153-157. CrossRef Medline
65. Szatkowski M, AttwellD (1994) Triggering and execution of neuronal death in brain ischaemia: two phases of glutamate release by different mechanisms. Trends Neurosci 17:359-365. CrossRef Medline
66. Szydlowska K, Gozdz A, Dabrowski M, Zawadzka M, Kaminska B (2010) Prolonged activation of ERK triggers glutamate-induced apoptosis of astrocytes: neuroprotective effect of FK506. J Neurochem 113:904-918. CrossRef Medline
67. Tanaka K, Watase K, Manabe T, Yamada K, Watanabe M, Takahashi K, Iwama H, Nishikawa T, Ichihara N, Kikuchi T, Okuyama S, Kawashima N, Hori S, Takimoto M, Wada K (1997) Epilepsy and exacerbation of brain injury in mice lacking the glutamate transporter GLT-1. Science 276:1699-1702. CrossRef Medline
68. Vera-Portocarrero LP, Mills CD, Ye Z, Fullwood SD, McAdoo DJ, Hulsebosch CE, Westlund KN (2002) Rapid changes in expression of glutamate transporters after spinal cord injury. Brain Res 927:104-110. CrossRef Medline
69. Wang D, Zhao Y, Zhang Y, Zhang T, Shang X, Wang J, Liu Y, Kong Q, Sun B, Mu L, Liu X, Wang G, Li H (2013) Hypothermia protects against oxygen-glucose deprivation-induced neuronal injury by down-regulating the reverse transport of glutamate by astrocytes as mediated by neurons. Neuroscience 237:130-138. CrossRef Medline
70. Wanner IB, Anderson MA, Song B, Levine J, Fernandez A, Gray-Thompson Z, Ao Y, Sofroniew MV (2013) Glial scar borders are formed by newly proliferated, elongated astrocytes that interact to corral inflammatory and fibrotic cells via STAT3-dependent mechanisms after spinal cord injury. J Neurosci 33:12870-12886. CrossRef Medline
71. Weller ML, Stone IM, Goss A, Rau T, Rova C, Poulsen DJ (2008) Selective overexpression of excitatory amino acid transporter 2 (EAAT2) in astrocytes enhances neuroprotection from moderate but not severe hypoxiaischemia. Neuroscience 155:1204-1211. CrossRef Medline
72. Wrathall JR, Choiniere D, Teng YD (1994) Dose-dependent reduction of tissue loss and functional impairment after spinal cord trauma with the AMPA/kainate antagonist NBQX. J Neurosci 14:6598-6607. Medline
73. Wright MC, Son YJ (2007) Ciliary neurotrophic factor is not required for terminal sprouting and compensatory reinnervation of neuromuscular synapses: re-evaluation of CNTF null mice. Exp Neurol 205:437-448. CrossRef Medline
74. Wu Y, Satkunendrarajah K, Teng Y, Chow DS, Buttigieg J, Fehlings MG (2013) Delayed post-injury administration of riluzole is neuroprotective in a preclinical rodent model of cervical spinal cord injury. J Neurotrauma 30:441-452. CrossRef Medline
75. Xu GY, Hughes MG, Ye Z, Hulsebosch CE, McAdoo DJ (2004) Concentrations of glutamate released following spinal cord injury kill oligodendrocytes in the spinal cord. Exp Neurol 187:329-336. CrossRef Medline
76. Xu GY, Liu S, Hughes MG, McAdoo DJ (2008) Glutamate-induced losses of oligodendrocytes and neurons and activation of caspase-3 in the rat spinal cord. Neuroscience 153:1034-1047. CrossRef Medline
77. Yang Y, Gozen O, Watkins A, Lorenzini I, Lepore A, Gao Y, Vidensky S, Brennan J, Poulsen D, WonPark J, Li Jeon N, Robinson MB, Rothstein JD (2009) Presynaptic regulation of astroglial excitatory neurotransmitter transporter GLT1. Neuron 61:880-894. CrossRef Medline
78. Zolotukhin S, Byrne BJ, Mason E, Zolotukhin I, Potter M, Chesnut K, Summerford C, Samulski RJ, Muzyczka N (1999) Recombinant adenoassociated virus purification using novel methods improves infectious titer and yield. Gene Ther 6:973-985. CrossRef Medline