Rapamycin increases neuronal survival, reduces inflammation and astrocyte proliferation after spinal cord injury

Molecular and Cellular Neuroscience

Volumn 68, Issue , 2015, Pages 82-91

  Goldshmit, Yona ^a,b   Kanner, Sivan ^a   Zacs, Maria ^a   Frisca, Frisca ^b,c   Pinto, Alexander R ^b   Currie, Peter D ^b   Pinkas Kramarski, Ronit ^a  

^a TEL AVIV UNIVERSITY   (Israel)

^b Australian Regenerative Medicine Institute and Department of Anatomy and Developmental Biology   (Australia)

^c UNIVERSITY OF MELBOURNE   (Australia)

Author keywords

Akt; Astrogliosis; Inflammation; Neuronal survival; Rapamycin; Spinal cord injury

Indexed keywords

PROTEIN KINASE B; RAPAMYCIN; S6 KINASE; TUMOR NECROSIS FACTOR ALPHA; CD11B ANTIGEN; ELAV LIKE PROTEIN 3; GLIAL FIBRILLARY ACIDIC PROTEIN; IMMUNOSUPPRESSIVE AGENT; KI 67 ANTIGEN;

ADULT; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTE; CELL ACTIVATION; CELL PROLIFERATION; CELL REGENERATION; CELL SURVIVAL; CONTROLLED STUDY; DRUG MECHANISM; ENZYME INHIBITION; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; MACROPHAGE MIGRATION; MALE; MICROGLIA; MITOSIS INHIBITION; MOUSE; MYELITIS; NEUTROPHIL CHEMOTAXIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN SECRETION; SPINAL CORD INJURY; SPINAL CORD NERVE CELL; ANIMAL; C57BL MOUSE; CELL COUNT; CELL CULTURE; COMPLICATION; DISEASE MODEL; DRUG EFFECTS; GENE EXPRESSION REGULATION; INFLAMMATION; METABOLISM; NERVE CELL; PATHOLOGY; PHYSIOLOGY; RAT; TIME FACTOR;

ANIMALS; ANTIGENS, CD11B; ASTROCYTES; CELL COUNT; CELL SURVIVAL; CELLS, CULTURED; DISEASE MODELS, ANIMAL; ELAV-LIKE PROTEIN 3; GENE EXPRESSION REGULATION; GLIAL FIBRILLARY ACIDIC PROTEIN; HUMANS; IMMUNOSUPPRESSIVE AGENTS; INFLAMMATION; KI-67 ANTIGEN; MALE; MICE; MICE, INBRED C57BL; NEURONS; RATS; SIROLIMUS; SPINAL CORD INJURIES; TIME FACTORS;

EID: 84943273932     PISSN: 10447431     EISSN: 10959327     Source Type: Journal    
DOI: 10.1016/j.mcn.2015.04.006     Document Type: Article

References (35)

1. Angliker N., Ruegg M.A. In vivo evidence for mTORC2-mediated actin cytoskeleton rearrangement in neurons. Bioarchitecture 2013, 3:113-118.
2. Beattie M.S. Inflammation and apoptosis: linked therapeutic targets in spinal cord injury. Trends Mol. Med. 2004, 10:580-583.
3. Berger Z., Ravikumar B., Menzies F.M., Oroz L.G., Underwood B.R., Pangalos M.N., Schmitt I., Wullner U., Evert B.O., O'Kane C.J., Rubinsztein D.C. Rapamycin alleviates toxicity of different aggregate-prone proteins. Hum. Mol. Genet. 2006, 15:433-442.
4. Carloni S., Buonocore G., Balduini W. Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. Neurobiol. Dis. 2008, 32:329-339.
5. Chen H.C., Fong T.H., Hsu P.W., Chiu W.T. Multifaceted effects of rapamycin on functional recovery after spinal cord injury in rats through autophagy promotion, anti-inflammation, and neuroprotection. J. Surg. Res. 2013, 179:E203-E210.
6. Cicora F., Lausada N., Vasquez D.N., Cicora P., Zalazar G., Gonzalez P., Palti G., Raimondi C. Sirolimus in kidney transplant donors and clinical and histologic improvement in recipients: rat model. Transplant. Proc. 2010, 42:365-370.
7. Codeluppi S., Svensson C.I., Hefferan M.P., Valencia F., Silldorff M.D., Oshiro M., Marsala M., Pasquale E.B. The Rheb-mTOR pathway is upregulated in reactive astrocytes of the injured spinal cord. J. Neurosci. 2009, 29:1093-1104.
8. Das F., Bera A., Ghosh-Choudhury N., Abboud H.E., Kasinath B.S., Choudhury G.G. TGF beta-induced deptor suppression recruits mTORC1 and not mTORC2 to enhance Collagen I (alpha 2) gene expression. PLoS One 2014, 9.
9. Diskin T., Tal-Or P., Erlich S., Mizrachy L., Alexandrovich A., Shohami E., Pinkas-Kramarski R. Closed head injury induces upregulation of Beclin 1 at the cortical site of injury. J. Neurotrauma 2005, 22:750-762.
10. Erlich S., Shohami E., Pinkas-Kramarski R. Neurodegeneration induces upregulation of Beclin 1. Autophagy 2006, 2:49-51.
11. Erlich S., Alexandrovich A., Shohami E., Pinkas-Kramarski R. Rapamycin is a neuroprotective treatment for traumatic brain injury. Neurobiol. Dis. 2007, 26:86-93.
12. Goldshmit Y., Galea M.P., Wise G., Bartlett P.F., Turnley A.M. Axonal regeneration and lack of astrocytic gliosis in EphA4-deficient mice. J. Neurosci. 2004, 24:10064-10073.
13. Goldshmit Y., Spanevello M.D., Tajouri S., Li L., Rogers F., Pearse M., Galea M., Bartlett P.F., Boyd A.W., Turnley A.M. EphA4 blockers promote axonal regeneration and functional recovery following spinal cord injury in mice. PLoS One 2011, 6:e24636.
14. Herzog N., Shein-Idelson M., Hanein Y. Optical validation of in vitro extra-cellular neuronal recordings. J. Neural Eng. 2011, 8:056008.
15. Hu L.Y., Sun Z.G., Wen Y.M., Cheng G.Z., Wang S.L., Zhao H.B., Zhang X.R. Atp-mediated protein kinase B Akt/mammalian target of rapamycin mTOR/P70 ribosomal S6 protein p70S6 kinase signaling pathway activation promotes improvement of locomotor function after spinal cord injury in rats. Neuroscience 2010, 169:1046-1062.
16. Kamada Y., Sekito T., Ohsumi Y. Autophagy in yeast: a TOR-mediated response to nutrient starvation. TOR: Target of Rapamycin 2003, 279:73-84.
17. Kanno H., Ozawa H., Sekiguchi A., Yamaya S., Itoi E. Induction of autophagy and autophagic cell death in damaged neural tissue after acute spinal cord injury in mice. Spine 2011, 36:E1427-E1434.
18. Klionsky D.J., Emr S.D. Autophagy as a regulated pathway of cellular degradation. Science 2000, 290:1717-1721.
19. Laplante M., Sabatini D.M. mTOR signaling at a glance. J. Cell Sci. 2009, 122:3589-3594.
20. Larsen K.E., Sulzer D. Autophagy in neurons: a review. Histol. Histopathol. 2002, 17:897-908.
21. Norsted Gregory E., Delaney A., Abdelmoaty S., Bas D.B., Codeluppi S., Wigerblad G., Svensson C.I. Pentoxifylline and propentofylline prevent proliferation and activation of the mammalian target of rapamycin and mitogen activated protein kinase in cultured spinal astrocytes. J. Neurosci. Res. 2013, 91:300-312.
22. Ogier-Denis E., Codogno P. Autophagy: a barrier or an adaptive response to cancer. Biochim. Biophys. Acta 2003, 603:113-128.
23. Pinto A.R., Chandran A., Rosenthal N.A., Godwin J.W. Isolation and analysis of single cells from the mouse heart. J. Immunol. Methods 2013, 393:74-80.
24. Puyal J., Vaslin A., Mottier V., Clarke P.G.H. Postischemic treatment of neonatal cerebral ischemia should target autophagy. Ann. Neurol. 2009, 66:378-389.
25. Rami A., Langhagen A., Steiger S. Focal cerebral ischemia induces upregulation of Beclin 1 and autophagy-like cell death. Neurobiol. Dis. 2008, 29:132-141.
26. Ravikumar B., Vacher C., Berger Z., Davies J.E., Luo S.Q., Oroz L.G., Scaravilli F., Easton D.F., Duden R., O'Kane C.J., Rubinsztein D.C. Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease. Nat. Genet. 2004, 36:585-595.
27. Reggiori F., Klionsky D.J. Autophagy in the eukaryotic cell. Eukaryot Cell 2002, 1:11-21.
28. Silver J., Miller J.H. Regeneration beyond the glial scar. Nat. Rev. Neurosci. 2004, 5:146-156.
29. Smith C.M., Chen Y., Sullivan M.L., Kochanek P.M., Clark R.S. Autophagy in acute brain injury: feast, famine, or folly?. Neurobiol. Dis. 2011, 43:52-59.
30. Song Y., Xue H., Liu T., Liu J., Chen D. Rapamycin plays a neuroprotective effect after spinal cord injury via anti-inflammatory effects. J. Biochem. Mol. Toxicol. Jan 2015, 29(1):29-34.
31. Tachibana T., Shiiya N., Kunihara T., Wakamatsu Y., Kudo A.F., Ooka T., Watanabe S., Yasuda K. Immunophilin ligands FK506 and cyclosporine A improve neurologic and histopathologic outcome after transient spinal cord ischemia in rabbits. J. Thorac. Cardiovasc. Surg. 2005, 129:123-128.
32. Tang P., Hou H., Zhang L., Lan X., Mao Z., Liu D., He C., Du H., Zhang L. Autophagy reduces neuronal damage and promotes locomotor recovery via inhibition of apoptosis after spinal cord injury in rats. Mol. Neurobiol. 2014, 49:276-287.
33. Vignot S., Faivre S., Aguirre D., Raymond E. MTOR-targeted therapy of cancer with rapamycin derivatives. Ann. Oncol. 2005, 16:525-537.
34. Wang C.W., Klionsky D.J. The molecular mechanism of autophagy. Mol. Med. 2003, 9:65-76.
35. Xie L., Sun F., Wang J., Mao X., Xie L., Yang S.H., Su D.M., Simpkins J.W., Greenberg D.A., Jin K. mTOR signaling inhibition modulates macrophage/microglia-mediated neuroinflammation and secondary injury via regulatory T cells after focal ischemia. J. Immunol. 2014, 192:6009-6019.