N-methyl-D-aspartate but not glutamate induces the release of hydroxyl radicals in the neonatal rat: Modulation by group I metabotropic glutamate receptors

Cambonie, Gilles; Laplanche, Loı̈c; Kamenka, Jean-Marc; Barbanel, Gérard

doi:10.1002/1097-4547(20001001)62:1<84::aid-jnr9>3.0.co;2-u

Cited by 23 publications

(11 citation statements)

References 48 publications

(76 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…NMDA-induced neurotoxicity is reduced by group I-mGluRs [231,[241][242][243][244]. NMDA-induced free oxygen radicals release is blocked by group I-mGluR agonists in neonatal rats [245], a regulation that vanishes in mature animals [246]. Nitric oxide (NO)-or ischemia-induced cell death is decreased or even totally blocked by stimulation of group I-mGluRs [247][248][249][250][251][252].…”

Section: Mglurs and Toxicity/neuroprotectionmentioning

confidence: 90%

Metabotropic Glutamate Receptors as Drug Targets

Récasens¹,

Guiramand²,

Aimar³

et al. 2007

CDT

View full text Add to dashboard Cite

L-glutamate (Glu), the main excitatory amino acid neurotransmitter in the mammalian central nervous system, is involved in many physiological functions, including learning and memory, but also in toxic phenomena occurring in numerous degenerative or neurological diseases. These functions mainly result from its interaction with Glu receptors (GluRs). The broad spectrum of roles played by glutamate derived from the large number of membrane receptors, which are currently classified in two main categories, ionotropic (iGluRs) and metabotropic (mGluRs) receptors. The iGluRs are ion channels, permeant to Na(+) (Ca(2+)) while the mGluRs belongs to the superfamily of G-protein coupled receptors (GPCRs). Despite continuous efforts over more than two decades, the use of iGluR agonists or antagonists to improve or inhibit excitatory transmission in pathological states still remains a major challenge, though the discovery and development of recent molecules may prove it worthwhile. This probably results form the vital role of fast excitatory transmission in many fundamental physiological functions. Since the discovery of mGluRs, hope has emerged. Indeed, mGluRs are mainly involved in the regulation of fast excitatory transmission. Consequently, it was logically thought that modulating mGluRs with agonists or antagonists might lead to more subtle regulation of fast excitatory transmission than by directly blocking iGluRs. As a result of intensive investigation, new drugs permitting to discriminate between these receptors have emerged. Moreover, a new class of molecules acting as negative or positive allosteric modulators or mGluRs is now available and appears to be promising. In the following, we will review the classification of mGluRs and the functions in which mGluRs are involved. We will focus on their potential as therapeutic targets for improving numerous physiological functions and for different neurodegenerative and neuropsychiatric disorders, which are related to malfunction of Glu signaling in human beings.

show abstract

Section: Mglurs and Toxicity/neuroprotectionmentioning

confidence: 90%

Metabotropic Glutamate Receptors as Drug Targets

Récasens¹,

Guiramand²,

Aimar³

et al. 2007

CDT

View full text Add to dashboard Cite

show abstract

“…Overproduction of toxic oxygen‐derived free radicals after excessive stimulation of glutamatergic receptors is associated frequently with glutamate neurotoxicity in adults. We reported previously, however, that glutamate did not induce any hydroxyl radicals (·OH) release in 7‐day‐old rats but, unexpectedly, completely prevented the ·OH response to NMDA itself (Cambonie et al, 2000). Furthermore, the depressive effect of glutamate on ·OH production persisted until at least 15 days postnatally, with an apparent switch taking place after Day 21 from an immature to an adult ·OH response to both NMDA and glutamate (Cambonie et al, 2001).…”

mentioning

confidence: 92%

Prenatal infection obliterates glutamate‐related protection against free hydroxyl radicals in neonatal rat brain

Cambonie

Hirbec

Michaud

et al. 2003

J of Neuroscience Research

Self Cite

View full text Add to dashboard Cite

Prenatal infection constitutes an important risk factor for brain injury, in both premature and full-term infants. Unfortunately, as the mechanisms involved are far from understood, no therapeutic strategy emerges to prevent the damage. We tested the hypothesis that administration of lipopolysaccharide (LPS) to gravid female rats enhanced glutamate-induced oxidative stress in brain of pups. A microdialysis probe was implanted into the striatum of 14-day-old animals and the release of hydroxyl radicals (.OH) in the perfusion medium was evaluated. Glutamate promoted a delayed.OH release in the offspring of dams given LPS, contrasting with the.OH decreases observed in control animals. A similar response occurred after infusion of (R,S)-3,5-dihydroxyphenylglycine (DHPG), a Group I metabotropic glutamate receptor (mGluR) agonist. This response was not consecutive to a remote activation of N-methyl-D-aspartate (NMDA) receptors, as it was unaffected by an NMDA receptor antagonist. Furthermore, the response to NMDA itself decreased in the offspring of dams given LPS. Massive amounts of DHPG, however, likely internalizing the mGlu receptor, still blunted the response to NMDA, as in controls. No quantitative variation occurred in mGluR1, mGluR5, or the NR1 subunit of the NMDA receptor between controls and neonates born from LPS-treated dams. Direct LPS injection into age-matched pups, by contrast, affected the response to neither glutamate nor DHPG. These results confirm that normally during perinatal development, the brain is protected from any oxidative stress resulting from excess glutamate, and the results support the hypothesis that maternal infection before delivery may lead to critical brain damage via the release of toxic free radicals.

show abstract

“…The effect of an increased [7] or pressure modified [20] inspired oxygen fraction (FiO 2 ), as well as the action of organic substrates as N-methyl-daspartate/glutamate [6], 1-methyl-4-phenylpyridinium/histidine [21] or carbon monoxide [8] or inorganic ions as iron (II) [22] (Fenton reaction) or aluminium [5] were studied. CYP-450 activity [23], as a liver dependent organic source for the 2,5-DHBA could be identified aside the local and systemic enzymatic conversion properties from xanthine oxidase [24] or substance P [25].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, trapping molecules as salicylic acid (SA) [5][6][7][8][9] or 4-hydroxybenzoic acid [10,11] are commonly used and has been recently reviewed [12]. Quantification of the reaction products of these molecules and ROS by chromatographic methods [5,13] are employed.…”

Section: Introductionmentioning

confidence: 99%