Neurological sequelae induced by alphavirus infection of the CNS are attenuated by treatment with the glutamine antagonist 6-diazo-5-oxo-l-norleucine

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• 作者：Michelle C. Potter (1) (2)
  Victoria K. Baxter (3) (6)
  Robert W. Mathey (1)
  Jesse Alt (1)
  Camilo Rojas (1) (3)
  Diane E. Griffin (6)
  Barbara S. Slusher (1) (2) (4) (5)
  
  1. Brain Science Institute ; Johns Hopkins University School of Medicine ; Baltimore ; MD ; 21205 ; USA
  2. Department of Neurology ; Johns Hopkins University School of Medicine ; Baltimore ; MD ; 21205 ; USA
  3. Department of Molecular and Comparative Pathobiology ; Johns Hopkins University School of Medicine ; Baltimore ; MD ; 21205 ; USA
  6. W. Harry Feinstone Department of Molecular Microbiology and Immunology ; Johns Hopkins Bloomberg School of Public Health ; Baltimore ; MD ; 21205 ; USA
  4. Department of Psychiatry ; Johns Hopkins University School of Medicine ; Baltimore ; MD ; 21205 ; USA
  5. Department of Neuroscience ; Johns Hopkins University School of Medicine ; Baltimore ; MD ; 21205 ; USA
  
• 关键词：Sindbis virus ; Alphavirus ; Encephalomyelitis ; Fear conditioning ; Hippocampus ; 6 ; Diazo ; 5 ; oxo ; L ; norleucine (DON)
• 刊名：Journal of NeuroVirology
• 出版年：2015
• 出版时间：April 2015
• 年：2015
• 卷：21
• 期：2
• 页码：159-173
• 全文大小：1,674 KB
• 参考文献：1. Adhikari, A (2014) Distributed circuits underlying anxiety. Front Behav Neurosci 8: pp. 112 CrossRef
  2. Amaral, DC, Rachid, MA, Vilela, MC, Campos, RD, Ferreira, GP, Rodrigues, DH, Lacerda-Queiroz, N, Miranda, AS, Costa, VV, Campos, MA, Kroon, EG, Teixeira, MM, Teixeira, AL (2011) Intracerebral infection with dengue-3 virus induces meningoencephalitis and behavioral changes that precede lethality in mice. J Neuroinflammation 8: pp. 23 CrossRef
  3. Binder, GK, Griffin, DE (2001) Interferon-纬-mediated site-specific clearance of alphavirus from CNS neurons. Science 293: pp. 303-306 CrossRef
  4. Bruyn, HB, Lennette, EH (1953) Western equine encephalitis in infants; a report on three cases with sequelae. Calif Med 79: pp. 362-366
  5. Colombo, SL, Palacios-Callender, M, Frakich, N, Leon, J, Schmitt, CA, Boorn, L, Davis, N, Moncada, S (2010) Anaphase-promoting complex/cyclosome-Cdh1 coordinates glycolysis and glutaminolysis with transition to S phase in human T lymphocytes. Proc Natl Acad Sci U S A 107: pp. 18868-18873 CrossRef
  6. Crawley, JN (2007) What鈥檚 wrong with my mouse? : behavioral phenotyping of transgenic and knockout mice. Wiley-Interscience, Hoboken CrossRef
  7. Earhart, RH, Koeller, JM, Davis, HL (1982) Phase I trial of 6-diazo-5-oxo-L-norleucine (DON) administered by 5-day courses. Cancer Treat Rep 66: pp. 1215-1217
  8. Earhart, RH, Amato, DJ, Chang, AY, Borden, EC, Shiraki, M, Dowd, ME, Comis, RL, Davis, TE, Smith, TJ (1990) Phase II trial of 6-diazo-5-oxo-L-norleucine versus aclacinomycin-A in advanced sarcomas and mesotheliomas. Invest New Drugs 8: pp. 113-119 CrossRef
  9. Earnest, MP, Goolishian, HA, Calverley, JR, Hayes, RO, Hill, HR (1971) Neurologic, intellectual, and psychologic sequelae following western encephalitis. A follow-up study of 35 cases. Neurology 21: pp. 969-974 CrossRef
  10. Finley, KH, Longshore, WA, Palmer, RJ, Cook, RE, Riggs, N (1955) Western equine and St. Louis encephalitis; preliminary report of a clinical follow-up study in California. Neurology 5: pp. 223-235 CrossRef
  11. Fitting, S, Ignatowska-Jankowska, BM, Bull, C, Skoff, RP, Lichtman, AH, Wise, LE, Fox, MA, Su, J, Medina, AE, Krahe, TE, Knapp, PE, Guido, W, Hauser, KF (2013) Synaptic dysfunction in the hippocampus accompanies learning and memory deficits in human immunodeficiency virus type-1 Tat transgenic mice. Biol Psychiatry 73: pp. 443-453 CrossRef
  12. Goeldner, C, Reiss, D, Wichmann, J, Kieffer, BL, Ouagazzal, A-M (2009) Activation of nociceptin opioid peptide (NOP) receptor impairs contextual fear learning in mice through glutamatergic mechanisms. Neurobiol Learn Mem 91: pp. 393-401 CrossRef
  13. Gould, TJ, McCarthy, MM, Keith, RA (2002) MK-801 disrupts acquisition of contextual fear conditioning but enhances memory consolidation of cued fear conditioning. Behav Pharmacol 13: pp. 287-294 CrossRef
  14. Greene, IP, Lee, E-Y, Prow, N, Ngwang, B, Griffin, D (2008) Protection from fatal viral encephalomyelitis: AMPA receptor antagonists have a direct effect on the inflammatory response to infection. Proc Natl Acad Sci U S A 105: pp. 3575-3580 CrossRef
  15. Griffin, DE (2010) Emergence and re-emergence of viral diseases of the central nervous system. Prog Neurobiol 91: pp. 95-101 CrossRef
  16. Griffin, DE Alphaviruses. In: Knipe, DM, Howley, PM eds. (2013) Fields virology. Lippincott Williams & Wilkins, Philadelphia, pp. 652-686
  17. Gubler, DJ (2002) The global emergence/resurgence of arboviral diseases as public health problems. Arch Med Res 33: pp. 330-342 CrossRef
  18. Havert, MB, Schofield, B, Griffin, DE, Irani, DN (2000) Activation of divergent neuronal cell death pathways in different target cell populations during neuroadapted sindbis virus infection of mice. J Virol 74: pp. 5352-5356 CrossRef
  19. Holt, W, Maren, S (1999) Muscimol inactivation of the dorsal hippocampus impairs contextual retrieval of fear memory. J Neurosci 19: pp. 9054-9062
  20. Jackson, AC, Moench, TR, Griffin, DE, Johnson, RT (1987) The pathogenesis of spinal cord involvement in the encephalomyelitis of mice caused by neuroadapted Sindbis virus infection. Lab Invest 56: pp. 418-423
  21. Jurgens, HA, Amancherla, K, Johnson, RW (2012) Influenza infection induces neuroinflammation, alters hippocampal neuron morphology, and impairs cognition in adult mice. J Neurosci 32: pp. 3958-3968 CrossRef
  22. Kim, JJ, Jung, MW (2006) Neural circuits and mechanisms involved in Pavlovian fear conditioning: a critical review. Neurosci Biobehav Rev 30: pp. 188-202 CrossRef
  23. Kimura, T, Griffin, DE (2003) Extensive immune-mediated hippocampal damage in mice surviving infection with neuroadapted Sindbis virus. Virology 311: pp. 28-39 CrossRef
  24. Kovach, JS, Eagan, RT, Powis, G, Rubin, J, Creagan, ET, Moertel, CG (1981) Phase I and pharmacokinetic studies of DON. Cancer Treat Rep 65: pp. 1031-1036
  25. Lambrechts, L, Scott, TW, Gubler, DJ (2010) Consequences of the expanding global distribution of Aedes albopictus for dengue virus transmission. PLoS Negl Trop Dis 4: pp. e646 CrossRef
  26. Levine, B, Griffin, DE (1992) Persistence of viral RNA in mouse brains after recovery from acute alphavirus encephalitis. J Virol 66: pp. 6429-6435
  27. Levine, B, Hardwick, JM, Trapp, BD, Crawford, TO, Bollinger, RC, Griffin, DE (1991) Antibody-mediated clearance of alphavirus infection from neurons. Science 254: pp. 856-860 CrossRef
  28. Logue, SF, Paylor, R, Wehner, JM (1997) Hippocampal lesions cause learning deficits in inbred mice in the Morris water maze and conditioned-fear task. Behav Neurosci 111: pp. 104-113 CrossRef
  29. Lustig, S, Jackson, AC, Hahn, CS, Griffin, DE, Strauss, EG, Strauss, JH (1988) Molecular basis of Sindbis virus neurovirulence in mice. J Virol 62: pp. 2329-2336
  30. Maren S, Phan KL, Liberzon I (2013) The contextual brain: implications for fear conditioning, extinction and psychopathology. 1鈥?2. doi: 10.1038/nrn3492
  31. Marlatt, MW, Potter, MC, Lucassen, PJ, Praag, H (2012) Running throughout middle-age improves memory function, hippocampal neurogenesis, and BDNF levels in female C57BL/6J mice. Devel Neurobio 72: pp. 943-952 CrossRef
  32. McArthur, JC, Steiner, J, Sacktor, N, Nath, A (2010) HIV-associated neurocognitive disorders: 鈥渕ind the gap. Ann Neurol NA鈥揘A.
  33. Melnikova, T, Savonenko, A, Wang, Q, Liang, X, Hand, T, Wu, L, Kaufmann, WE, Vehmas, A, Andreasson, KI (2006) Cycloxygenase-2 activity promotes cognitive deficits but not increased amyloid burden in a model of Alzheimer鈥檚 disease in a sex-dimorphic pattern. Neuroscience 141: pp. 1149-1162 CrossRef
  34. Metcalf, TU, Griffin, DE (2011) Alphavirus-induced encephalomyelitis: antibody-secreting cells and viral clearance from the nervous system. J Virol 85: pp. 11490-11501 CrossRef
  35. Millichap, JG (2008) Etiologic classification of attention-deficit/hyperactivity disorder. Pediatrics 121: pp. e358-e365 CrossRef
  36. Nadler, JV, Perry, BW, Cotman, CW (1978) Intraventricular kainic acid preferentially destroys hippocampal pyramidal cells. Nature 271: pp. 676-677 CrossRef
  37. Nargi-Aizenman, JL, Havert, MB, Zhang, M, Irani, DN, Rothstein, JD, Griffin, DE (2004) Glutamate receptor antagonists protect from virus-induced neural degeneration. Ann Neurol 55: pp. 541-549 CrossRef
  38. Newsholme, EA, Crabtree, B, Ardawi, MS (1985) Glutamine metabolism in lymphocytes: its biochemical, physiological and clinical importance. Q J Exp Physiol 70: pp. 473-489 CrossRef
  39. Nozyce, ML (2006) A behavioral and cognitive profile of clinically stable HIV-infected children. Pediatrics 117: pp. 763-770 CrossRef
  40. Okun, E, Griffioen, K, Barak, B, Roberts, NJ, Castro, K, Pita, MA, Cheng, A, Mughal, MR, Wan, R, Ashery, U, Mattson, MP (2010) Toll-like receptor 3 inhibits memory retention and constrains adult hippocampal neurogenesis. Proc Natl Acad Sci U S A 107: pp. 15625-15630 CrossRef
  41. Olney, JW, Fuller, T, Gubareff, T (1979) Acute dendrotoxic changes in the hippocampus of kainate treated rats. Brain Res 176: pp. 91-100 CrossRef
  42. Phillips, RG, LeDoux, JE (1992) Differential contribution of amygdala and hippocampus to cued and contextual fear conditioning. Behav Neurosci 106: pp. 274-285 CrossRef
  43. Phillips, RG, LeDoux, JE (1994) Lesions of the dorsal hippocampal formation interfere with background but not foreground contextual fear conditioning. Learn Mem 1: pp. 34-44
  44. Potter MC, Yuan C, Ottenritter C, Mughal M, van Praag H (2010) Exercise is not beneficial and may accelerate symptom onset in a mouse model of Huntington鈥檚 disease. PLoS Curr 2:RRN1201. doi: 10.1371/currents.RRN1201
  45. Potter, MC, Figuera-Losada, M, Rojas, C, Slusher, BS (2013) Targeting the glutamatergic system for the treatment of HIV-associated neurocognitive disorders. J Neuroimmune Pharmacol 8: pp. 594-607 CrossRef
  46. Provenzale JM, vanLandingham KE, Lewis DV, Mukundan S, White LE (2008) Extrahippocampal involvement in human herpesvirus 6 encephalitis depicted at MR imaging. Radiology 249:955鈥?63
  47. Rowell, JFJ, Griffin, DED (1999) The inflammatory response to nonfatal Sindbis virus infection of the nervous system is more severe in SJL than in BALB/c mice and is associated with low levels of IL-4 mRNA and high levels of IL-10-producing CD4+ T cells. J Immunol 162: pp. 1624-1632
  48. Rudy, JW (1993) Contextual conditioning and auditory cue conditioning dissociate during development. Behav Neurosci 107: pp. 887-891 CrossRef
  49. Sanders, MJ, Wiltgen, BJ, Fanselow, MS (2003) The place of the hippocampus in fear conditioning. Eur J Pharmacol 463: pp. 217-223 CrossRef
  50. Shelton, LM, Huysentruyt, LC, Seyfried, TN (2010) Glutamine targeting inhibits systemic metastasis in the VM-M3 murine tumor model. Int J Cancer 127: pp. 2478-2485 CrossRef
  51. Shijie, J, Takeuchi, H, Yawata, I, Harada, Y, Sonobe, Y, Doi, Y, Liang, J, Hua, L, Yasuoka, S, Zhou, Y, Noda, M, Kawanokuchi, J, Mizuno, T, Suzumura, A (2009) Blockade of glutamate release from microglia attenuates experimental autoimmune encephalomyelitis in mice. Tohoku J Exp Med 217: pp. 87-92 CrossRef
  52. Silverman, MA, Misasi, J, Smole, S, Feldman, HA, Cohen, AB, Santagata, S, McManus, M, Ahmed, AA (2013) Eastern equine encephalitis in children, Massachusetts and New Hampshire, USA, 1970鈥?010. Emerg Infect Dis 19: pp. 194-201 CrossRef
  53. Sklaroff, RB, Casper, ES, Magill, GB, Young, CW (1980) Phase I study of 6-diazo-5-oxo-L-norleucine (DON). Cancer Treat Rep 64: pp. 1247-1251
  54. Souba, WW (1993) Glutamine and cancer. Ann Surg 218: pp. 715-728 CrossRef
  55. Steele, KE, Reed, DS, Glass, PJ, Hart, MK, Ludwig, GV, Pratt, WD, Parker, MD, Smith, JF Alphavirus encephalitides. In: Dembek, ZF eds. (2007) Medical aspects of biological warfare. Office of the Surgeon General, US Army Medical Department Center and School, Borden Institute, Washington, pp. 1-30
  56. Umpierre, AD, Remigio, GJ, Dahle, EJ, Bradford, K, Alex, AB, Smith, MD, West, PJ, White, HS, Wilcox, KS (2014) Impaired cognitive ability and anxiety-like behavior following acute seizures in the Theiler鈥檚 virus model of temporal lobe epilepsy. Neurobiol Dis 64: pp. 98-106 CrossRef
  57. Hurk, AF, Ritchie, SA, Mackenzie, JS (2009) Ecology and geographical expansion of Japanese encephalitis virus. Annu Rev Entomol 54: pp. 17-35 CrossRef
  58. Villari, P, Spielman, A, Komar, N, McDowell, M, Timperi, RJ (1995) The economic burden imposed by a residual case of eastern encephalitis. Am J Trop Med Hyg 52: pp. 8-13
  59. Wang, R, Dillon, CP, Shi, LZ, Milasta, S, Carter, R, Finkelstein, D, McCormick, LL, Fitzgerald, P, Chi, H, Munger, J, Green, DR (2011) The transcription factor Myc controls metabolic reprogramming upon T lymphocyte activation. Immunity 35: pp. 871-882 CrossRef
  60. Weaver, SC, Reisen, WK (2010) Present and future arboviral threats. Antiviral Res 85: pp. 328-345 CrossRef
  61. Weaver, SC, Salas, R, Rico-Hesse, R, Ludwig, GV, Oberste, MS, Boshell, J, Tesh, RB (1996) Re-emergence of epidemic Venezuelan equine encephalomyelitis in South America. VEE Study Group Lancet 348: pp. 436-440
  62. Wiltgen, BJ (2006) Context fear learning in the absence of the hippocampus. J Neurosci 26: pp. 5484-5491 CrossRef
  
• 刊物主题：Neurosciences; Virology; Infectious Diseases; Immunology; Neurology;
• 出版者：Springer US
• ISSN：1538-2443

文摘

Recovery from encephalomyelitis induced by infection with mosquito-borne alphaviruses is associated with a high risk of lifelong debilitating neurological deficits. Infection of mice with the prototypic alphavirus, Sindbis virus, provides an animal model with which to study disease mechanisms and examine potential therapeutics. Infectious virus is cleared from the brain within a week after infection, but viral RNA is cleared slowly and persists for the life of the animal. However, no studies have examined the effect of infection on neurocognitive function over time. In the present study, we examined neurocognitive function at different phases of infection in 5-week-old C57BL/6 mice intranasally inoculated with Sindbis virus. At the peak of active virus infection, mice demonstrated hyperactivity, decreased anxiety, and marked hippocampal-dependent memory deficits, the latter of which persisted beyond clearance of infectious virus and resolution of clinical signs of disease. Previous studies indicate that neuronal damage during alphavirus encephalomyelitis is primarily due to inflammatory cell infiltration and glutamate excitotoxicity rather than directly by virus infection. Therefore, mice were treated with 6-diazo-5-oxo-l-norleucine (DON), a glutamine antagonist that can suppress both the immune response and excitotoxicity. Treatment with DON decreased inflammatory cell infiltration and cell death in the hippocampus and partially prevented development of clinical signs and neurocognitive impairment despite the presence of infectious virus and high viral RNA levels. This study presents the first report of neurocognitive sequelae in mice with alphavirus encephalomyelitis and provides a model system for further elucidation of the pathogenesis of virus infection and assessment of potential therapies.