MTOR inhibition suppresses established epilepsy in a mouse model of cortical dysplasia

Epilepsia

Volumn 56, Issue 4, 2015, Pages 636-646

  Nguyen, Lena H ^a,b   Brewster, Amy L ^c   Clark, Madeline E ^a,b   Regnier Golanov, Angelique ^a,b   Sunnen, C Nicole ^d   Patil, Vinit V ^a,b   D'Arcangelo, Gabriella ^e   Anderson, Anne E ^a,b  

^a BAYLOR COLLEGE OF MEDICINE   (United States)

^b TEXAS CHILDREN S HOSPITAL   (United States)

^c PURDUE UNIVERSITY   (United States)

^d UNIVERSITY OF THE SCIENCES   (United States)

^e RUTGERS UNIVERSITY   (United States)

Author keywords

Astrogliosis; Malformation of cortical development; Microgliosis; Rapamycin; Seizures

Indexed keywords

MAMMALIAN TARGET OF RAPAMYCIN; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 2; RAPAMYCIN; MTOR PROTEIN, MOUSE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PTEN PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE;

ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTOSIS; CONTROLLED STUDY; CORTICAL DYSPLASIA; DISEASE SEVERITY; ELECTROENCEPHALOGRAPHY; EPILEPSY; EPILEPTOGENESIS; FEMALE; GLIOSIS; HIPPOCAMPUS; IMMUNOHISTOCHEMISTRY; MALE; MOUSE; NEUROPATHOLOGY; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; SURVIVAL; WESTERN BLOTTING; ANIMAL; ANTAGONISTS AND INHIBITORS; DEFICIENCY; DISEASE MODEL; KNOCKOUT MOUSE; MALFORMATIONS OF CORTICAL DEVELOPMENT; METABOLISM;

ANIMALS; DISEASE MODELS, ANIMAL; EPILEPSY; FEMALE; MALE; MALFORMATIONS OF CORTICAL DEVELOPMENT; MICE; MICE, KNOCKOUT; PTEN PHOSPHOHYDROLASE; SIROLIMUS; TOR SERINE-THREONINE KINASES;

EID: 84927573931     PISSN: 00139580     EISSN: 15281167     Source Type: Journal    
DOI: 10.1111/epi.12946     Document Type: Article

References (41)

1. Crino PB, Chou K,. Epilepsy and cortical dysplasias. Curr Treat Options Neurol 2000; 2: 543-552.
2. Laplante M, Sabatini DM,. mTOR signaling in growth control and disease. Cell 2012; 149: 274-293.
3. Orlova KA, Crino PB,. The tuberous sclerosis complex. Ann N Y Acad Sci 2010; 1184: 87-105.
4. Lee JH, Huynh M, Silhavy JL, et al. De novo somatic mutations in components of the PI3K-AKT3-mTOR pathway cause hemimegalencephaly. Nat Genet 2012; 44: 941-945.
5. Orlova KA, Parker WE, Heuer GG, et al. STRADalpha deficiency results in aberrant mTORC1 signaling during corticogenesis in humans and mice. J Clin Invest 2010; 120: 1591-1602.
6. Puffenberger EG, Strauss KA, Ramsey KE, et al. Polyhydramnios, megalencephaly and symptomatic epilepsy caused by a homozygous 7-kilobase deletion in LYK5. Brain 2007; 130: 1929-1941.
7. Wong M,. Mammalian target of rapamycin (mTOR) pathways in neurological diseases. Biomed J 2013; 36: 40-50.
8. Wong M, Crino PB,. mTOR and epileptogenesis in developmental brain malformations. In, Noebels JL, Avoli M, Rogawski MA, et al. (Eds) Jasper's basic mechanisms of the epilepsies. Bethesda, MD: National Center for Biotechnology Information (US), 2012.
9. Zeng LH, Rensing NR, Wong M,. The mammalian target of rapamycin signaling pathway mediates epileptogenesis in a model of temporal lobe epilepsy. J Neurosci 2009; 29: 6964-6972.
10. Huang X, Zhang H, Yang J, et al. Pharmacological inhibition of the mammalian target of rapamycin pathway suppresses acquired epilepsy. Neurobiol Dis 2010; 40: 193-199.
11. Ljungberg MC, Bhattacharjee MB, Lu Y, et al. Activation of mammalian target of rapamycin in cytomegalic neurons of human cortical dysplasia. Ann Neurol 2006; 60: 420-429.
12. Aronica E, Boer K, Baybis M, et al. Co-expression of cyclin D1 and phosphorylated ribosomal S6 proteins in hemimegalencephaly. Acta Neuropathol 2007; 114: 287-293.
13. Miyata H, Chiang AC, Vinters HV,. Insulin signaling pathways in cortical dysplasia and TSC-tubers: tissue microarray analysis. Ann Neurol 2004; 56: 510-519.
14. Baybis M, Yu J, Lee A, et al. mTOR cascade activation distinguishes tubers from focal cortical dysplasia. Ann Neurol 2004; 56: 478-487.
15. Sha LZ, Xing XL, Zhang D, et al. Mapping the spatio-temporal pattern of the mammalian target of rapamycin (mTOR) activation in temporal lobe epilepsy. PLoS ONE 2012; 7: e39152.
16. Sosunov AA, Wu X, McGovern RA, et al. The mTOR pathway is activated in glial cells in mesial temporal sclerosis. Epilepsia 2012; 53 (Suppl. 1): 78-86.
17. Sarbassov DD, Ali SM, Sengupta S, et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell 2006; 22: 159-168.
18. Backman SA, Stambolic V, Suzuki A, et al. Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease. Nat Genet 2001; 29: 396-403.
19. Kwon CH, Zhu X, Zhang J, et al. Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease. Nat Genet 2001; 29: 404-411.
20. Ljungberg MC, Sunnen CN, Lugo JN, et al. Rapamycin suppresses seizures and neuronal hypertrophy in a mouse model of cortical dysplasia. Dis Model Mech 2009; 2: 389-398.
21. Sunnen CN, Brewster AL, Lugo JN, et al. Inhibition of the mammalian target of rapamycin blocks epilepsy progression in NS-Pten conditional knockout mice. Epilepsia 2011; 52: 2065-2075.
22. Brewster AL, Lugo JN, Patil VV, et al. Rapamycin reverses status epilepticus-induced memory deficits and dendritic damage. PLoS ONE 2013; 8: e57808.
23. Hoeffer CA, Klann E,. mTOR signaling: at the crossroads of plasticity, memory and disease. Trends Neurosci 2010; 33: 67-75.
24. Guertin DA, Sabatini DM,. Defining the role of mTOR in cancer. Cancer Cell 2007; 12: 9-22.
25. Talos DM, Sun H, Zhou X, et al. 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: e35885.
26. Dello Russo C, Lisi L, Feinstein DL, et al. mTOR kinase, a key player in the regulation of glial functions: relevance for the therapy of multiple sclerosis. Glia 2013; 61: 301-311.
27. Vezzani A, French J, Bartfai T, et al. The role of inflammation in epilepsy. Nat Rev Neurol 2011; 7: 31-40.
28. Kettenmann H, Hanisch UK, Noda M, et al. Physiology of microglia. Physiol Rev 2011; 91: 461-553.
29. Bajorat R, Wilde M, Sellmann T, et al. Seizure frequency in pilocarpine-treated rats is independent of circadian rhythm. Epilepsia 2011; 52: e118-e122.
30. Goffin K, Nissinen J, Van Laere K, et al. Cyclicity of spontaneous recurrent seizures in pilocarpine model of temporal lobe epilepsy in rat. Exp Neurol 2007; 205: 501-505.
31. Williams PA, White AM, Clark S, et al. Development of spontaneous recurrent seizures after kainate-induced status epilepticus. J Neurosci 2009; 29: 2103-2112.
32. Kadam SD, White AM, Staley KJ, et al. Continuous electroencephalographic monitoring with radio-telemetry in a rat model of perinatal hypoxia-ischemia reveals progressive post-stroke epilepsy. J Neurosci 2010; 30: 404-415.
33. Lasarge CL, Danzer SC,. Mechanisms regulating neuronal excitability and seizure development following mTOR pathway hyperactivation. Front Mol Neurosci 2014; 7: 18.
34. Buckmaster PS, Ingram EA, Wen X,. Inhibition of the mammalian target of rapamycin signaling pathway suppresses dentate granule cell axon sprouting in a rodent model of temporal lobe epilepsy. J Neurosci 2009; 29: 8259-8269.
35. Ming GL, Song H,. Adult neurogenesis in the mammalian brain: significant answers and significant questions. Neuron 2011; 70: 687-702.
36. Pun RY, Rolle IJ, Lasarge CL, et al. Excessive activation of mTOR in postnatally generated granule cells is sufficient to cause epilepsy. Neuron 2012; 75: 1022-1034.
37. Devinsky O, Vezzani A, Najjar S, et al. Glia and epilepsy: excitability and inflammation. Trends Neurosci 2013; 36: 174-184.
38. Krueger DA, Wilfong AA, Holland-Bouley K, et al. Everolimus treatment of refractory epilepsy in tuberous sclerosis complex. Ann Neurol 2013; 74: 679-687.
39. Zeng LH, Xu L, Gutmann DH, et al. Rapamycin prevents epilepsy in a mouse model of tuberous sclerosis complex. Ann Neurol 2008; 63: 444-453.
40. Zhou J, Blundell J, Ogawa S, et al. Pharmacological inhibition of mTORC1 suppresses anatomical, cellular, and behavioral abnormalities in neural-specific Pten knock-out mice. J Neurosci 2009; 29: 1773-1783.
41. Hailer NP,. Immunosuppression after traumatic or ischemic CNS damage: it is neuroprotective and illuminates the role of microglial cells. Prog Neurobiol 2008; 84: 211-233.