QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 25, 2004, 24(34):7566-7575; doi:10.1523/JNEUROSCI.2002-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (43) Citing Articles via Google Scholar Google Scholar Articles by Darman, J. Articles by Kerr, D. A. Search for Related Content PubMed PubMed Citation Articles by Darman, J. Articles by Kerr, D. A.

 Previous Article  |  Next Article 

Neurobiology of Disease
Viral-Induced Spinal Motor Neuron Death Is Non-Cell-Autonomous and Involves Glutamate Excitotoxicity

Jessica Darman,^1,3 Stephanie Backovic,^1,3 Sonny Dike,¹ Nicholas J. Maragakis,¹ Chitra Krishnan,¹ Jeffrey D. Rothstein,^1,2 David N. Irani,^1,3 and Douglas A. Kerr^1,3

Departments of ¹Neurology and ²Neurosciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287, and ³Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland 21205

Neuroadapted Sindbis virus (NSV) is a neurotropic virus capable of inducing the death of spinal motor neurons in mice and rats. In this study we investigated the mechanisms that underlie NSV-induced motor neuron death. We found that many degenerating spinal motor neurons were not infected directly with NSV, suggesting that bystander cell death occurs. An excitotoxic mechanism was confirmed when blockade of calcium-permeable AMPA receptors attenuated motor neuron death both in vitro and in vivo. Blockade of astroglial glutamate reuptake potentiated NSV-induced motor neuron loss in vivo, suggesting that astrocyte-mediated removal of perisynaptic glutamate is important in limiting NSV-induced excitotoxic injury. Astroglial glutamate transport was reduced markedly in the spinal cord during NSV infection, in advance of motor neuron injury in susceptible mice. In contrast, we found 5.6-fold elevated glutamate uptake in the spinal cords of mice resistant to NSV-induced paralysis. Likewise, minocycline markedly increased spinal cord glutamate transport and protected mice from NSV-induced motor neuron death. These studies suggest that NSV infection triggers a cascade of events in the spinal cord resulting in impaired astrocytic glutamate transport and excitotoxic injury of motor neurons mediated via calciumpermeable AMPA receptors. Similar changes may occur in other motor neuron disorders such as amyotrophic lateral sclerosis or West Nile Virus-induced poliomyelitis, suggesting a common tissue injury pathway.

Key words: encephalomyelitis; motor neuron; paralysis; spinal; transport; virus; glutamate

---

Received May 24, 2004; revised July 15, 2004; accepted July 16, 2004.

This article has been cited by other articles:

				V. Siddharthan, H. Wang, N. E. Motter, J. O. Hall, R. D. Skinner, R. T. Skirpstunas, and J. D. Morrey Persistent West Nile Virus Associated with a Neurological Sequela in Hamsters Identified by Motor Unit Number Estimation J. Virol., May 1, 2009; 83(9): 4251 - 4261. [Abstract] [Full Text] [PDF]

				I. P. Greene, E.-Y. Lee, N. Prow, B. Ngwang, and D. E. Griffin Protection from fatal viral encephalomyelitis: AMPA receptor antagonists have a direct effect on the inflammatory response to infection PNAS, March 4, 2008; 105(9): 3575 - 3580. [Abstract] [Full Text] [PDF]

				M. Michaelis, M. C. Kleinschmidt, H. W. Doerr, and J. Cinatl Jr Minocycline inhibits West Nile virus replication and apoptosis in human neuronal cells J. Antimicrob. Chemother., November 1, 2007; 60(5): 981 - 986. [Abstract] [Full Text] [PDF]

				T. Kielian, N. Esen, S. Liu, N. K. Phulwani, M. M. Syed, N. Phillips, K. Nishina, A. L. Cheung, J. D. Schwartzman, and J. J. Ruhe Minocycline Modulates Neuroinflammation Independently of Its Antimicrobial Activity in Staphylococcus aureus-Induced Brain Abscess Am. J. Pathol., October 1, 2007; 171(4): 1199 - 1214. [Abstract] [Full Text] [PDF]

				A. C. Jackson, C. A. Scott, J. Owen, S. C. Weli, and J. P. Rossiter Therapy with Minocycline Aggravates Experimental Rabies in Mice J. Virol., June 15, 2007; 81(12): 6248 - 6253. [Abstract] [Full Text] [PDF]

				S. C. Weli, C. A. Scott, C. A. Ward, and A. C. Jackson Rabies virus infection of primary neuronal cultures and adult mice: failure to demonstrate evidence of excitotoxicity. J. Virol., October 1, 2006; 80(20): 10270 - 10273. [Abstract] [Full Text] [PDF]

				I. Ivanovska and J. M. Hardwick Viruses activate a genetically conserved cell death pathway in a unicellular organism J. Cell Biol., August 1, 2005; 170(3): 391 - 399. [Abstract] [Full Text] [PDF]

				A. C. Jackson Recovery from Rabies N. Engl. J. Med., June 16, 2005; 352(24): 2549 - 2550. [Full Text] [PDF]

				T. Uo, Y. Kinoshita, and R. S. Morrison Neurons Exclusively Express N-Bak, a BH3 Domain-only Bak Isoform That Promotes Neuronal Apoptosis J. Biol. Chem., March 11, 2005; 280(10): 9065 - 9073. [Abstract] [Full Text] [PDF]

				R. Diem, M. B. Sattler, D. Merkler, I. Demmer, K. Maier, C. Stadelmann, H. Ehrenreich, and M. Bahr Combined therapy with methylprednisolone and erythropoietin in a model of multiple sclerosis Brain, February 1, 2005; 128(2): 375 - 385. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help