mTOR pathway inhibition prevents neuroinflammation and neuronal death in a mouse model of cerebral palsy

Neurobiology of Disease

Volumn 85, Issue , 2016, Pages 144-154

  Srivastava, Isha N ^a   Shperdheja, Jona ^a   Baybis, Marianna ^a   Ferguson, Tanya ^a   Crino, Peter B ^a  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Autophagy; Cell death; Cerebral palsy; Inflammation; Microglia; MTOR; Rapamycin

Indexed keywords

BECLIN 1; CASPASE 3; CELL PROTEIN; CHLOROQUINE; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IBA 1 PROTEIN; INITIATION FACTOR 4E BINDING PROTEIN 1; LC3II PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; PF 4708671; PROTEIN SERINE THREONINE KINASE INHIBITOR; RAPAMYCIN; S6 KINASE; UNCLASSIFIED DRUG; ANTIINFLAMMATORY AGENT; LIPOPOLYSACCHARIDE; MTOR PROTEIN, MOUSE; NEUROPROTECTIVE AGENT; TARGET OF RAPAMYCIN KINASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APOPTOSIS; ARTICLE; ASTROCYTOSIS; AUTOPHAGY; BRAIN ATROPHY; BRAIN INJURY; CELL ACTIVATION; CELL COUNT; CELL DEATH; CELL LOSS; CELL SURVIVAL; CELLULAR DISTRIBUTION; CEREBRAL PALSY; CONTROLLED STUDY; DRUG EFFECT; DRUG RESPONSE; ENZYME PHOSPHORYLATION; HIPPOCAMPAL CA1 REGION; HIPPOCAMPAL CA3 REGION; MICROGLIA; MOUSE; NERVE CELL; NERVOUS SYSTEM INFLAMMATION; NEUROPROTECTION; NONHUMAN; OLIGODENDROGLIA; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN EXPRESSION; SIGNAL TRANSDUCTION; TREATMENT DURATION; ANIMAL; BRAIN; C57BL MOUSE; DISEASE MODEL; DRUG EFFECTS; HYPOXIC ISCHEMIC ENCEPHALOPATHY; IMMUNOMODULATION; METABOLISM; NEWBORN; PATHOLOGY; PATHOPHYSIOLOGY; PHYSIOLOGY;

ANIMALS; ANIMALS, NEWBORN; ANTI-INFLAMMATORY AGENTS; BRAIN; CELL DEATH; CEREBRAL PALSY; DISEASE MODELS, ANIMAL; HYPOXIA-ISCHEMIA, BRAIN; LIPOPOLYSACCHARIDES; MICE, INBRED C57BL; NEUROIMMUNOMODULATION; NEURONS; NEUROPROTECTIVE AGENTS; SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84946431008     PISSN: 09699961     EISSN: 1095953X     Source Type: Journal    
DOI: 10.1016/j.nbd.2015.10.001     Document Type: Article

References (59)

1. Allan S.M., Rothwell N.J. Cytokines and acute neurodegeneration. Nat. Rev. Neurosci. 2001, 2:734-744. 10.1038/35094583.
2. Auer R.N., Jensen M.L., Whishaw I.Q. Neurobehavioral deficit due to ischemic brain damage limited to half of the CA1 sector of the hippocampus. J. Neurosci. 1989, 9:1641-1647.
3. Bax M., Goldstein M., Rosenbaum P., Leviton A., Paneth N., Dan B., Jacobsson B., Damiano D., Executive Committee for the Definition of Cerebral Palsy Proposed definition and classification of cerebral palsy, April 2005. Dev. Med. Child Neurol. 2005, 47:571-576.
4. Bax M., Tydeman C., Flodmark O. Clinical and MRI correlates of cerebral palsy: the European Cerebral Palsy Study. JAMA 2006, 296:1602-1608.
5. Buckley K.M., Hess D.L., Sazonova I.Y., Periyasamy-Thandavan S., Barrett J.R., Kirks R., Grace H., Kondrikova G., Johnson M.H., Hess D.C., Schoenlein P.V., Hoda M.N., Hill W.D. Rapamycin up-regulation of autophagy reduces infarct size and improves outcomes in both permanent MCAL, and embolic MCAO, murine models of stroke. Exp. Transl. Stroke Med. 2014, 6:8. 10.1186/2040-7378-6-8.
6. Carloni S., Buonocore G., Balduini W. Protective role of autophagy in neonatal hypoxia-ischemia induced brain injury. Neurobiol. Dis. 2008, 32:329-339. 10.1016/j.nbd.2008.07.022.
7. Carloni S., Girelli S., Scopa C., Buonocore G., Longini M., Balduini W. Activation of autophagy and Akt/CREB signaling play an equivalent role in the neuroprotective effect of rapamycin in neonatal hypoxia-ischemia. Autophagy 2010, 6:366-377.
8. Chen H., Xiong T., Qu Y., Zhao F., Ferriero D., Mu D. mTOR activates hypoxia-inducible factor-1α and inhibits neuronal apoptosis in the developing rat brain during the early phase after hypoxia-ischemia. Neurosci. Lett. 2012, 507:118-123. 10.1016/j.neulet.2011.11.058.
9. Chen W., Jadhav V., Tang J., Zhang J.H. HIF-1 Alpha Inhibition Ameliorates Neonatal Brain Damage After Hypoxic-Ischemic Injury. Acta Neurochirurgica Supplements 2009, 395-399. Springer.
10. Curatolo P., Seri S., Verdecchia M., Bombardieri R. Infantile spasms in tuberous sclerosis complex. Brain Dev. 2001, 23:502-507. 10.1016/S0387-7604(01)00300-X.
11. Czeh M., Gressens P., Kaindl A.M. The yin and yang of microglia. Dev. Neurosci. 2011, 33:199-209. 10.1159/000328989.
12. Deguchi K., Mizuguchi M., Takashima S. Immunohistochemical expression of tumor necrosis factor alpha in neonatal leukomalacia. Pediatr. Neurol. 1996, 14:13-16.
13. Delaporte B., Labrune M., Imbert M.C., Dehan M. Early echographic findings in non-hemorrhagic periventricular leukomalacia of the premature infant. Pediatr. Radiol. 1985, 15:82-84.
14. Di R., Wu X., Chang Z., Zhao X., Feng Q., Lu S., Luan Q., Hemmings B.A., Li X., Yang Z. S6K inhibition renders cardiac protection against myocardial infarction through PDK1 phosphorylation of Akt. Biochem. J. 2012, 441:199-207. 10.1042/BJ20110033.
15. Eklind S., Arvidsson P., Hagberg H., Mallard C. The role of glucose in brain injury following the combination of lipopolysaccharide or lipoteichoic acid and hypoxia-ischemia in neonatal rats. Dev. Neurosci. 2004, 26:61-67. 10.1159/000080713.
16. Fleiss B., Gressens P. Tertiary mechanisms of brain damage: a new hope for treatment of cerebral palsy?. Lancet Neurol. 2012, 11:556-566. 10.1016/S1474-4422(12)70058-3.
17. Fujioka M., Nishio K., Miyamoto S., Hiramatsu K.-I., Sakaki T., Okuchi K., Taoka T., Fujioka S. Hippocampal damage in the human brain after cardiac arrest. Cerebrovasc. Dis. 2000, 10:2-7. 10.1159/000016018.
18. Girard S., Kadhim H., Beaudet N., Sarret P., Sébire G. Developmental motor deficits induced by combined fetal exposure to lipopolysaccharide and early neonatal hypoxia/ischemia: a novel animal model for cerebral palsy in very premature infants. Neuroscience 2009, 158:673-682. 10.1016/j.neuroscience.2008.10.032.
19. Goorden S.M.I., van Woerden G.M., van der Weerd L., Cheadle J.P., Elgersma Y. Cognitive deficits in Tsc1+/-mice in the absence of cerebral lesions and seizures. Ann. Neurol. 2007, 62:648-655. 10.1002/ana.21317.
20. Graham E.M., Holcroft C.J., Rai K.K., Donohue P.K., Allen M.C. Neonatal cerebral white matter injury in preterm infants is associated with culture positive infections and only rarely with metabolic acidosis. Am. J. Obstet. Gynecol. 2004, 191:1305-1310. 10.1016/j.ajog.2004.06.058.
21. Hall M.N. mTOR-What Does It Do?. Transplant. Proc. 2008, 40:S5-S8. 10.1016/j.transproceed.2008.10.009.
22. Horn M., Schlote W. Delayed neuronal death and delayed neuronal recovery in the human brain following global ischemia. Acta Neuropathol. (Berl.) 1992, 85:79-87.
23. Hosokawa N., Hara T., Kaizuka T., Kishi C., Takamura A., Miura Y., Iemura S., Natsume T., Takehana K., Yamada N., Guan J.-L., Oshiro N., Mizushima N. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol. Biol. Cell 2009, 20:1981-1991. 10.1091/mbc.E08-12-1248.
24. Hu Y., Chen G., Wan H., Zhang Z., Zhi H., Liu W., Qian X., Chen M., Wen L., Gao F. A rat pup model of cerebral palsy induced by prenatal inflammation and hypoxia. Neural Regen. Res. 2013, 8.
25. Hudson C.C., Liu M., Chiang G.G., Otterness D.M., Loomis D.C., Kaper F., Giaccia A.J., Abraham R.T. Regulation of hypoxia-inducible factor 1α expression and function by the mammalian target of rapamycin. Mol. Cell. Biol. 2002, 22:7004-7014. 10.1128/MCB.22.20.7004-7014.2002.
26. Jaakkola P., Mole D.R., Tian Y.-M., Wilson M.I., Gielbert J., Gaskell S.J., von Kriegsheim A., Hebestreit H.F., Mukherji M., Schofield C.J., Maxwell P.H., Pugh ‡.C.W., Ratcliffe ‡.P.J. Targeting of HIF-α to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science 2001, 292:468-472. 10.1126/science.1059796.
27. Jung C.H., Jun C.B., Ro S.-H., Kim Y.-M., Otto N.M., Cao J., Kundu M., Kim D.-H. ULK-Atg13-FIP200 complexes mediate mTOR Signaling to the autophagy machinery. Mol. Biol. Cell 2009, 20:1992-2003. 10.1091/mbc.E08-12-1249.
28. Kadhim H., Tabarki B., Verellen G., De Prez C., Rona A.M., Sébire G. Inflammatory cytokines in the pathogenesis of periventricular leukomalacia. Neurology 2001, 56:1278-1284.
29. Kaur C., Ling E.A. Periventricular white matter damage in the hypoxic neonatal brain: role of microglial cells. Prog. Neurobiol. 2009, 87:264-280. 10.1016/j.pneurobio.2009.01.003.
30. Keogh J.M., Badawi N. The origins of cerebral palsy. Curr. Opin. Neurol. 2006, 19:129-134. 10.1097/01.wco.0000218227.35560.0d.
31. Kiffin R., Bandyopadhyay U., Cuervo A.M. Oxidative stress and autophagy. Antioxid. Redox Signal. 2006, 8:152-162. 10.1089/ars.2006.8.152.
32. Kirby R.S., Wingate M.S., Van Naarden Braun K., Doernberg N.S., Arneson C.L., Benedict R.E., Mulvihill B., Durkin M.S., Fitzgerald R.T., Maenner M.J., Patz J.A., Yeargin-Allsopp M. Prevalence and functioning of children with cerebral palsy in four areas of the United States in 2006: a report from the autism and developmental disabilities monitoring network. Res. Dev. Disabil. 2011, 32:462-469. 10.1016/j.ridd.2010.12.042.
33. Krägeloh-Mann I., Horber V. The role of magnetic resonance imaging in elucidating the pathogenesis of cerebral palsy: a systematic review. Dev. Med. Child Neurol. 2007, 49:144-151.
34. Krägeloh-Mann I., Helber A., Mader I., Staudt M., Wolff M., Groenendaal F., DeVries L. Bilateral lesions of thalamus and basal ganglia: origin and outcome. Dev. Med. Child Neurol. 2002, 44:477-484.
35. Kusaba H., Ghosh P., Derin R., Buchholz M., Sasaki C., Madara K., Longo D.L. Interleukin-12-induced interferon-gamma production by human peripheral blood T cells is regulated by mammalian target of rapamycin (mTOR). J. Biol. Chem. 2005, 280:1037-1043. 10.1074/jbc.M405204200.
36. Lein E.S., Hawrylycz M.J., Ao N., Ayres M., Bensinger A., Bernard A., Boe A.F., Boguski M.S., et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature 2007, 445:168-176. 10.1038/nature05453.
37. Levine B., Klionsky D.J. Development by self-digestion: molecular mechanisms and biological functions of autophagy. Dev. Cell 2004, 6:463-477. 10.1016/S1534-5807(04)00099-1.
38. Maxwell P.H., Wiesener M.S., Chang G.-W., Clifford S.C., Vaux E.C., Cockman M.E., Wykoff C.C., Pugh C.W., Maher E.R., Ratcliffe P.J. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 1999, 399:271-275. 10.1038/20459.
39. Nelson K.B., Grether J.K. Potentially asphyxiating conditions and spastic cerebral palsy in infants of normal birth weight. Am. J. Obstet. Gynecol. 1998, 179:507-513. 10.1016/S0002-9378(98)70387-4.
40. Ng S., Wu Y.-T., Chen B., Zhou J., Shen H.-M. Impaired autophagy due to constitutive mTOR activation sensitizes TSC2-null cells to cell death under stress. Autophagy 2011, 7:1173-1186. 10.4161/auto.7.10.16681.
41. Pakula A.T., Van Naarden Braun K., Yeargin-Allsopp M. Cerebral palsy: classification and epidemiology. Phys. Med. Rehabil. Clin. N. Am. 2009, 20:425-452. 10.1016/j.pmr.2009.06.001.
42. Papadakis M., Hadley G., Xilouri M., Hoyte L.C., Nagel S., McMenamin M.M., Tsaknakis G., Watt S.M., Drakesmith C.W., Chen R., Wood M.J.A., Zhao Z., Kessler B., Vekrellis K., Buchan A.M. Tsc1 (hamartin) confers neuroprotection against ischemia by inducing autophagy. Nat. Med. 2013, 19:351-357. 10.1038/nm.3097.
43. Pearce L.R., Alton G.R., Richter D.T., Kath J.C., Lingardo L., Chapman J., Hwang C., Alessi D.R. Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem. J. 2010, 431:245-255. 10.1042/BJ20101024.
44. Rami A., Sims J., Botez G., Winckler J. Spatial resolution of phospholipid scramblase 1 (PLSCR1), caspase-3 activation and DNA-fragmentation in the human hippocampus after cerebral ischemia. Neurochem. Int. 2003, 43:79-87. 10.1016/S0197-0186(02)00194-8.
45. Rees S., Inder T. Fetal and neonatal origins of altered brain development. Early Hum. Dev. 2005, 81:753-761. 10.1016/j.earlhumdev.2005.07.004.
46. Russo C.D., Lisi L., Tringali G., Navarra P. Involvement of mTOR kinase in cytokine-dependent microglial activation and cell proliferation. Biochem. Pharmacol. 2009, 78:1242-1251. 10.1016/j.bcp.2009.06.097.
47. Schmidt-Kastner R., Freund T.F. Selective vulnerability of the hippocampus in brain ischemia. Neuroscience 1991, 40:599-636. 10.1016/0306-4522(91)90001-5.
48. Sharma A., Hoeffer C.A., Takayasu Y., Miyawaki T., McBride S.M., Klann E., Zukin R.S. Dysregulation of mTOR signaling in Fragile X syndrome. J. Neurosci. 2010, 30:694-702. 10.1523/JNEUROSCI.3696-09.2010.
49. Sheldon R.A., Lee C.L., Jiang X., Knox R.N., Ferriero D.M. Hypoxic preconditioning protection is eliminated in HIF-1α knockout mice subjected to neonatal hypoxia-ischemia. Pediatr. Res. 2014, 76:46-53. 10.1038/pr.2014.53.
50. Shen Y., Liu X.-B., Pleasure D.E., Deng W. Axon-glia synapses are highly vulnerable to white matter injury in the developing brain. J. Neurosci. Res. 2012, 90:105-121. 10.1002/jnr.22722.
51. Shen Y., Plane J.M., Deng W. Mouse models of periventricular leukomalacia. J. Vis. Exp. JoVE 2010, 10.3791/1951.
52. Sugawara T., Lewén A., Noshita N., Gasche Y., Chan P.H. Effects of global ischemia duration on neuronal, astroglial, oligodendroglial, and microglial reactions in the vulnerable hippocampal CA1 subregion in rats. J. Neurotrauma 2002, 19:85-98. 10.1089/089771502753460268.
53. Talos D.M., Sun H., Zhou X., Fitzgerald E.C., Jackson M.C., Klein P.M., Lan V.J., Joseph A., Jensen F.E. The interaction between early life epilepsy and autistic-like behavioral consequences: a role for the mammalian target of rapamycin (mTOR) pathway. PLoS One 2012, 7. 10.1371/journal.pone.0035885.
54. Tan S., Drobyshevsky A., Jilling T., Ji X., Ullman L.M., Englof I., Derrick M. Model of cerebral palsy in the perinatal rabbit. J. Child Neurol. 2005, 20:972-979.
55. Weichhart T., Costantino G., Poglitsch M., Rosner M., Zeyda M., Stuhlmeier K.M., Kolbe T., Stulnig T.M., Hörl W.H., Hengstschläger M., Müller M., Säemann M.D. The TSC-mTOR signaling pathway regulates the innate inflammatory response. Immunity 2008, 29:565-577. 10.1016/j.immuni.2008.08.012.
56. Wheater M., Rennie J.M. Perinatal infection is an important risk factor for cerebral palsy in very-low-birthweight infants. Dev. Med. Child Neurol. 2000, 364-367. (null, doi:null).
57. Wu Y.-T., Tan H.-L., Huang Q., Ong C.-N., Shen H.-M. Activation of the PI3K-Akt-mTOR signaling pathway promotes necrotic cell death via suppression of autophagy. Autophagy 2009, 5:824-834.
58. Zeng L.-H., Xu L., Gutmann D.H., Wong M. Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann. Neurol. 2008, 63:444-453. 10.1002/ana.21331.
59. Zhong H., Chiles K., Feldser D., Laughner E., Hanrahan C., Georgescu M.M., Simons J.W., Semenza G.L. Modulation of hypoxia-inducible factor 1alpha expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res. 2000, 60:1541-1545.