The excitotoxic effect of NMDA on human lymphocyte immune function

Mashkina, Anna P.; Tyulina, O. V.; Solovyova, T.I.; Kovalenko, Elena I.; Kanevski, Leonid M.; Johnson, Peter; Boldyrev, Alexander A.

doi:10.1016/j.neuint.2007.04.009

Cited by 48 publications

(35 citation statements)

References 19 publications

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“…NMDA receptor subunits are found on resting rodent and human T lymphocytes. NMDA receptors are involved in modulating T cell functions including control of growth and adhesion to the extracellular matrix [47] , as well as cytokine production [26,48] . In the present study, blockade of the NMDA receptor channel was associated with increased expression of Foxp3, a transcription factor characteristic of regulatory T cells.…”

Section: Discussionmentioning

confidence: 99%

The N-Methyl-<i>D</i>-Aspartic Acid Receptor Antagonist Memantine Ameliorates and Delays the Development of Arthritis by Enhancing Regulatory T Cells

et al. 2012

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The neuroendocrine impact on rheumatoid arthritis is not yet fully described although numerous neurotransmitters are shown to act as inflammatory modulators. One of these is the excitatory transmitter glutamate (Glu). In this study, the influence of the Glu receptor (GluR)-mediated effects on collagen-induced arthritis (CIA) was investigated. CIA was induced in DBA/1 mice by immunization with chicken collagen type II (CII). Mice were exposed to the following GluR antagonists: group 1, the N-methyl-D-aspartic acid (NMDA) receptor channel blocker memantine; group 2, the metabotropic GluR antagonist AIDA, and group 3, the excitatory amino acid receptor antagonist kynurenic acid (KA). Arthritis was evaluated clinically and histologically and compared to PBS-treated controls. The effects of treatment on T cell populations and the levels of anti-CII and anti-citrullinated peptide antibodies were evaluated. Memantine treatment significantly improved the course of CIA, reducing synovitis (p = 0.007) and the frequency of erosions (p = 0.007). Memantine treatment up-regulated the expression of Foxp3 in spleen CD4+ T cells followed by an increase in CD4+CD25+ regulatory T cells. The other GluR antagonists, AIDA and KA, had no effect on CIA. These results demonstrate that blockade of the NMDA receptor channel with memantine delays and attenuates the development of arthritis, probably by promoting the development of regulatory T lymphocytes.

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Section: Discussionmentioning

confidence: 99%

The N-Methyl-<i>D</i>-Aspartic Acid Receptor Antagonist Memantine Ameliorates and Delays the Development of Arthritis by Enhancing Regulatory T Cells

et al. 2012

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“…Specifically, glutamate and glutamate receptors may play a role in the induction of immune responses. T lymphocytes express glutamate receptors, including ionotropic AMPA receptors (52)(53)(54)(55)(56). Dendritic cells, the major cells responsible for antigen presentation, release glutamate when in contact with T cells (57), and T cells respond to low doses of glutamate with increased Ca 2ϩ influx, proliferation, migration, and adhesion (52, 53, 58, 59), suggesting an important role for glutamate in modulating the immune response (60).…”

Section: Discussionmentioning

confidence: 99%

Protection from fatal viral encephalomyelitis: AMPA receptor antagonists have a direct effect on the inflammatory response to infection

Greene

Lee

Prow

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

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“…Through a breakdown of the glutamate/cystine antiporter concomitant reduction in glutathione synthesis, glutamate affects elevation of intracellular ROS in neurons (Ha and Park 2006) and peripheral lymphocytes (Tuneva et al 2003;Mashkina et al 2007).…”

Section: Discussionmentioning

confidence: 99%

Effects of one-day reperfusion after transient forebrain ischemia on circulatory system in the rat

Kravčuková¹,

Danielisová²,

Némethová³

et al. 2010

gpb

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Abstract. Although ischemia/reperfusion injury remains incompletely understood, it appears that reactive oxygen species produced mainly during postischemic recirculation play a critical role. The present study examined the impact of forebrain ischemia and subsequent one-day reperfusion on several blood parameters. We determined glutamate concentration in whole blood, measured Cu/Zn-and Mn-SOD (superoxide dismutase) activity in blood cells as well as plasma, and investigated the prevalence of single and double strand breaks of lymphocyte DNA. The results of our experiment showed that the concentration of glutamic acid in whole blood was increased by about 25%. Antioxidant activity of total SOD and Cu/Zn-SOD was reduced in blood cells and plasma. Mn-SOD activity in blood cells was not affected by ischemic insult and one-day reperfusion, but we detected its significantly lower activity in samples of plasma. We observed a weakly reduced level of double and a significantly elevated level of single strand breaks of lymphocyte DNA.In conclusion, one day of recovery after the ischemic attack failed to return peripheral circulatory system to physiological conditions. Reduced antioxidant capacity in the blood and an elevated level of excitotoxic amino acid glutamate may cause lymphocyte DNA damage, and probably contribute to insufficient postischemic recovery of brain tissue.

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The excitotoxic effect of NMDA on human lymphocyte immune function

Cited by 48 publications

References 19 publications

The N-Methyl-<i>D</i>-Aspartic Acid Receptor Antagonist Memantine Ameliorates and Delays the Development of Arthritis by Enhancing Regulatory T Cells

The N-Methyl-<i>D</i>-Aspartic Acid Receptor Antagonist Memantine Ameliorates and Delays the Development of Arthritis by Enhancing Regulatory T Cells

Protection from fatal viral encephalomyelitis: AMPA receptor antagonists have a direct effect on the inflammatory response to infection

Effects of one-day reperfusion after transient forebrain ischemia on circulatory system in the rat

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