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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, March 22, 2006, 26(12):3220-3228; doi:10.1523/JNEUROSCI.3780-05.2006

This Article Full Text Full Text (PDF) Supplemental data 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 (23) Citing Articles via Google Scholar Google Scholar Articles by Alberdi, E. Articles by Matute, C. Search for Related Content PubMed PubMed Citation Articles by Alberdi, E. Articles by Matute, C.

 Previous Article  |  Next Article 

Cellular/Molecular
Activation of Kainate Receptors Sensitizes Oligodendrocytes to Complement Attack

Elena Alberdi, María Victoria Sánchez-Gómez, Iratxe Torre, María Domercq, Alberto Pérez-Samartín, Fernando Pérez-Cerdá, and Carlos Matute

Departamento de Neurociencias, Universidad del País Vasco, E-48940 Leioa, Vizcaya, Spain

Correspondence should be addressed to Carlos Matute, Departamento de Neurociencias, Universidad del País Vasco, Barrio de Sarriena s/n, 48940 Leioa, Spain. Email: carlos.matute{at}ehu.es

Glutamate excitotoxicity and complement attack have both been implicated separately in the generation of tissue damage in multiple sclerosis and in its animal model, experimental autoimmune encephalomyelitis. Here, we investigated whether glutamate receptor activation sensitizes oligodendrocytes to complement attack. We found that a brief incubation with glutamate followed by exposure to complement was lethal to oligodendrocytes in vitro and in freshly isolated optic nerves. Complement toxicity was induced by activation of kainate but not of AMPA receptors and was abolished by removing calcium from the medium during glutamate priming. Dose–response studies showed that sensitization to complement attack is induced by two distinct kainate receptor populations displaying high and low affinities for glutamate. Oligodendrocyte death by complement required the formation of the membrane attack complex, which in turn increased membrane conductance and induced calcium overload and mitochondrial depolarization as well as a rise in the level of reactive oxygen species. Treatment with the antioxidant Trolox and inhibition of poly(ADP-ribose) polymerase-1, but not of caspases, protected oligodendrocytes against damage induced by complement. These findings indicate that glutamate sensitization of oligodendrocytes to complement attack may contribute to white matter damage in acute and chronic neurological disorders.

Key words: kainate receptors; glutamate; complement; calcium; oxidative stress; oligodendrocytes

---

Received Sept. 7, 2005; revised Feb. 9, 2006; accepted Feb. 9, 2006.

Correspondence should be addressed to Carlos Matute, Departamento de Neurociencias, Universidad del País Vasco, Barrio de Sarriena s/n, 48940 Leioa, Spain. Email: carlos.matute{at}ehu.es

This article has been cited by other articles:

				E. E. Benarroch Oligodendrocytes: Susceptibility to injury and involvement in neurologic disease Neurology, May 19, 2009; 72(20): 1779 - 1785. [Full Text] [PDF]

				S. R. Hinson, S. F. Roemer, C. F. Lucchinetti, J. P. Fryer, T. J. Kryzer, J. L. Chamberlain, C. L. Howe, S. J. Pittock, and V. A. Lennon Aquaporin-4-binding autoantibodies in patients with neuromyelitis optica impair glutamate transport by down-regulating EAAT2 J. Exp. Med., October 27, 2008; 205(11): 2473 - 2481. [Abstract] [Full Text] [PDF]

				R.E. Gonsette Review: Oxidative stress and excitotoxicity: a therapeutic issue in multiple sclerosis? Multiple Sclerosis, January 1, 2008; 14(1): 22 - 34. [Abstract] [PDF]

				A. Verkhratsky and F. Kirchhoff NMDA Receptors in Glia Neuroscientist, February 1, 2007; 13(1): 28 - 37. [Abstract] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help