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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, December 3, 2003, 23(35):11094-11103

This Article Full Text Full Text (PDF) An erratum has been published 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 (9) Citing Articles via Google Scholar Google Scholar Articles by Glezer, I. Articles by Rivest, S. Search for Related Content PubMed PubMed Citation Articles by Glezer, I. Articles by Rivest, S.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Modulation of the Innate Immune Response by NMDA Receptors Has Neuropathological Consequences

Isaias Glezer,^1,2 Hakima Zekki,¹ Cristoforo Scavone,² and Serge Rivest¹

¹Laboratory of Molecular Endocrinology, Centre Hospitalier Université Laval Research Center, and Department of Anatomy and Physiology, Laval University, Québec, Canada G1V 4G2, and ²Department of Pharmacology, Institute of Biomedical Science, University of São Paulo, 05508-900 São Paulo, Brazil

The aim of this study was to determine whether glutamate receptors modulate the innate immune response in the brain of C3H/HeN and C3H/HeJ mice; the latter bear a loss of function in the toll-like receptor (TLR) 4 gene. Mice received an intrastriatal (IS) infusion of lipopolysaccharide (LPS), the exogenous ligand for TLR4, and were killed at several times thereafter. This treatment activated the transcription of a wide variety of genes involved in the control of the innate immune response. MK-801, an antagonist of NMDA glutamate receptor subtype, exacerbated the effects of the endotoxin in the brain of C3H/HeN mice but not in TLR4-deficient animals. The ipsilateral side of C3H/HeN mice exhibited stronger hybridization signals for the mRNA encoding TLR2, CD14, tumor necrosis factor-, and inhibitory factor-B at various times after the treatment combining MK-801 and LPS. This robust inflammatory response in the brain of C3H/HeN mice was not associated with any convincing signs of neurodegeneration or demyelination that was verified via numerous approaches and at time up to 2 weeks after injection. However, animals that received long-term IS infusion of LPS, together with MK-801, exhibited a significant increase in demyelination levels within the ipsilateral side. Our results demonstrate that binding of glutamate to its cognate NMDA receptor modulates LPS-induced innate immune reaction in a TLR4-dependent manner. This acute response may be crucial to eliminate bacterial cell wall components and minimizing tissue injury. However, sustained deregulation of proinflammatory signaling involving NMDA receptors leads to demyelination and is likely to be a mechanism participating in such pathological conditions.

Key words: innate immune response; in situ hybridization histochemistry; inflammation; lipopolysaccharide; proinflammatory cytokines; microglia; macrophages; glutamate; demyelination

---

Received Aug 29, 2003; revised October 1, 2003; accepted October 7, 2003.

This article has been cited by other articles:

				S.-H. Yeh, J.-J. Hung, P.-W. Gean, and W.-C. Chang Hypoxia-Inducible Factor-1{alpha} Protects Cultured Cortical Neurons from Lipopolysaccharide-Induced Cell Death via Regulation of NR1 Expression J. Neurosci., December 24, 2008; 28(52): 14259 - 14270. [Abstract] [Full Text] [PDF]

				J. Kang and S. Rivest MyD88-deficient bone marrow cells accelerate onset and reduce survival in a mouse model of amyotrophic lateral sclerosis J. Cell Biol., December 17, 2007; 179(6): 1219 - 1230. [Abstract] [Full Text] [PDF]

				G. Soucy, G. Boivin, F. Labrie, and S. Rivest Estradiol Is Required for a Proper Immune Response to Bacterial and Viral Pathogens in the Female Brain J. Immunol., May 15, 2005; 174(10): 6391 - 6398. [Abstract] [Full Text] [PDF]

				I. Glezer and S. Rivest Glucocorticoids: Protectors of the Brain during Innate Immune Responses Neuroscientist, December 1, 2004; 10(6): 538 - 552. [Abstract] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help