Comparison of the kinetics of the inward Ca(2+) ion flux to (S)-alpha-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid [(S)-AMPA] in cerebrocortical homogenates and that of the previously reported transmembrane Na(+) ion influx mediated by an AMPA receptor in hippocampal homogenates established that the agonist-induced opening of the AMPA receptor channels occurs in two kinetically distinguishable ...

Quinolinic acid, which is produced by macrophages and microglia, can kill neurons in vivo and in vitro. To test whether quinolinic acid is toxic to oligodendrocytes, glial cells cultured from the brains of 2-day-old rats were incubated with quinolinic acid at concentrations known to kill neurons. The cells were then ...

We have investigated the role of glutathione in mechanisms associated with excitatory amino acid signaling to the nuclear transcription factor activator protein-1 (AP1) in the brain using mice depleted of endogenous glutathione by prior treatment with 2-cyclohexen-1-one (CHX). In the hippocampus of animals treated with CHX 2 h before, a ...

Kynurenic acid (KYNA), an excitatory amino acid antagonist preferentially active at glycine binding site of the NMDA receptor, has been previously identified in the brain. This study was designed to examine its presence in the rabbit vitreous humor. Mean (+/- SD) level of KYNA in the vitreous was 22.3 +/- ...

L-2-Chloropropionic acid is selectively toxic to the cerebellum in rats; the granule cell necrosis observed within 48 h can be prevented by prior administration of MK-801. Short-term treatment (2 h) with L-2-chloropropionic acid has also been shown to activate the mitochondrial pyruvate dehydrogenase complex in fasted adult rats. This study ...

Olfactory receptors in basiconic and grooved-peg sensilla on the antenna of fifth-instar Triatoma infestans nymphs respond to host odours. Gas chromatography analyses of host odour extracts coupled to electrophysiological recordings from basiconic sensillum receptors indicate that nonanal is a constituent of sheep wool and chicken feather odour that stimulates one ...

Fifteen days after a striatal kainic acid (KA) injection, we have examined presynaptic modifications of dopamine and serotonin terminals in the striatum through (i) autoradiographic labeling of dopamine, serotonin and vesicular monoamine transporters respectively with 3H-mazindol, 3H-citalopram and 3H-dihydrotetrabenazine, and (ii) determination of the contents in dopamine, serotonin and their ...

The role of interleukin-6 in hippocampal tissue damage after injection with kainic acid, a rigid glutamate analogue inducing epileptic seizures, has been studied by means of interleukin-6 null mice. At 35mg/kg, kainic acid induced convulsions in both control (75%) and interleukin-6 null (100%) mice, and caused a significant mortality (62%) ...

Kynurenine 3-mono-oxygenase, one of the key enzymes of the "kynurenine pathway", catalyses the formation of 3-hydroxykynurenine and may direct the neo-synthesis of quinolinic and kynurenic acids. While 3-hydroxykynurenine and quinolinic acid have neurotoxic properties, kynurenic acid antagonizes excitotoxic neuronal death. Here we report that the expression and activity of kynurenine ...

Neuroscientific underpinnings and pharmacotherapeutic treatments of substance use disorders are rapidly developing areas of study. In particular, there have been exciting new developments in our understanding of the involvement of excitatory amino acid neurotransmitter systems and the opiate and serotonin systems in the pathophysiology of alcohol withdrawal, alcohol dependence, and ...

The role of excitatory amino acid transporter 1 in neonatal rat neuronal damage was studied following hypoxia-ischemia. To induce hypoxia-ischemia injury, rats on postnatal day 7 were exposed to 8 % oxygen for 2 h following unilateral common carotid artery ligation. According to brain damage scoring based on Cresyl Violet ...

In most tissues, including brain, a major proportion of the tryptophan which is not used for protein synthesis is metabolised along the kynurenine pathway. Long regarded as the route by which many mammals generate adequate amounts of the essential co-factor nicotinamide adenine dinucleotide, two components of the pathway are now ...

A brief exposure of hippocampal slices to L-quisqualic acid sensitizes CA1 pyramidal neurons 30-250-fold to depolarization by two classes of excitatory amino acid analogues: (1) those whose depolarizing effects are rapidly terminated following washout, e.g. L-2-amino-4-phosphonobutanoic acid (L-AP4) and L-2-amino-6-phosphonohexanoic acid (L-AP6) and (2) those whose depolarizing effects persist following ...

Inhibitors of kynurenine 3-hydroxylase have previously been used to increase endogenous levels of kynurenic acid, an excitatory amino acid receptor antagonist. In the present electrophysiological study PNU 156561A was utilized to elevate endogenous concentrations of kynurenic acid and subsequent effects on the firing pattern of dopamine (DA) neurons of rat ...

Intraspinal injection of quisqualic acid, a mixed kainic acid/2-amino-3(3-hydroxy-5-methylisoxazol-4-yl)propionic acid and metabotropic glutamate receptor agonist, produces an excitotoxic injury that leads to the onset of both spontaneous and evoked pain behavior as well as changes in spinal and cortical expression of opioid peptide mRNA, preprodynorphin and preproenkephalin. What characteristics of ...

BACKGROUND: The excitatory amino acid domoic acid, a glutamate and kainic acid analog, is the causative agent of amnesic shellfish poisoning in humans. No studies to our knowledge have investigated the potential contribution to short-term neurotoxicity of the brain microglia, a cell type that constitutes circa 10% of the total ...

Cardiac afferents are sensory neurons that mediate angina, pain that occurs when the heart receives insufficient blood supply for its metabolic demand (ischemia). These neurons display enormous acid-evoked depolarizing currents, and they fire action potentials in response to extracellular acidification that accompanies myocardial ischemia. Here we show that acid-sensing ion ...

The over-stimulation of excitatory amino acid receptors such as the glutamate AMPA receptor has been suggested to be associated with neurodegenerative disorders. Here we describe an original series of readily water soluble 4-oxo-imidazo[1,2-a] indeno[1,2-e]pyrazin-8- and -9-carboxylic (acetic) acid derivatives. One of these compounds, 4f, exhibited nanomolar binding affinity, potent competitive ...

The non-essential amino acids L-serine (Ser) and glycine (Gly) have recently been shown to exhibit specific actions in the nervous system. In the present study, L-Ser and Gly promoted the survival of cultured rat cerebrocortical neurons in a concentration-dependent manner as revealed by Alamar blue assay and microtubule-associated protein-2 (MAP2) ...

Glutamate (10(-7)m) and one of its non-NMDA receptor agonists, kainic acid (10(-4)m), were administered to rat cerebellar granular cell cultures, and the neuroprotective role of salicylic acid was examined. Glutamate induced 38.58 +/- 1.45% neuronal cell death while kainic acid induced only 21.4 +/- 2.01% despite being 1000 times more ...

Dendrotoxins, important pharmacological tools for studying K(+) channels, are potently convulsant in the central nervous system and evidence suggests that different members of the dendrotoxin family may act at pre- or post-synaptic sites. Using a combination of intrahippocampal infusion, microdialysis and electroencephalograph (EEG) recording, we have compared the effects of ...

It is shown in the present study that metyrapone (100 mg/kg), an inhibitor of corticosterone synthesis, given twice, 30 min before and 6 h after kainic acid (10 mg/kg) administration, blocks the kainic acid-evoked induction of heat shock proteins 72 kDa (HSP 70). Specifically, it was observed that metyrapone completely ...

Rat spinal cord slices produced kynurenic acid (KYNA) upon exposure to L-kynurenine. Aminooxyacetic acid, non-selective aminotransferase inhibitor, and L-glutamate, but neither N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-metyloisoxazolo-4-propionate (AMPA), nor kainate, diminished synthesis of KYNA. L-Glutamate action was less potent in spinal than in cortical slices. Metabotropic agonists, L-(+)-2-amino-4-phosphonobutyrate (L-AP4) and (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD), ...

Oxidative stress has been implicated in a variety of acute and chronic neurologic conditions, including epilepsy. Both the kainic acid and pilocarpine are useful models of temporal lobe epilepsy in rodents. As an index of lipid peroxidation the level thiobarbituric acid reactive substances (TBARS) was measured after the status epileticus ...

Our objective was to characterize the mechanism of action of intrastriatal infusion of domoic acid on extracellular dopamine levels, using in vivo dialysis in conscious and freely moving rats. The local infusion of domoic acid (500 microM) caused an increase (567.9+/-142.5%, versus basal) in dopamine extracellular levels associated with a ...

Fulicin is a D-amino acid-containing neuropeptide that has been thought to control male copulatory behavior in the land snail, Achatina fulica. In the present study, we demonstrated that the vagina and the oviduct of Achatina were densely innervated by fulicin-like immunoreactive neuronal fibers. We confirmed that fulicin was actually present ...

The epidemiology, clinical features, pathology, and mechanisms of action of basal ganglia neurotoxins are reviewed. Manganese, cyanide, hydrogen sulfide, methanol, carbon monoxide, 3-nitropropionic acid, MPTP, and annonaceae alkaloids are discussed. The probable mechanism of action for almost all basal ganglia neurotoxins is inhibition of mitochondrial function with destruction of the ...

The electroretinogram (ERG) was recorded from the Xenopus retina, to examine the effects of glycine and strychnine on these responses and to determine the origins of these changes. Glycine at concentrations between 0.1 and 10 mM reduced the b- and d-waves of the ERG in a dose-dependent manner, while strychnine ...

This study examined the protective effect of phenobarbital on kainic acid-induced deficits in acquisition learning. A single kainic acid injection (9 mg/kg i.p.) was administered five days prior to testing using the Morris water maze test. Kainic acid produced deficits in the acquisition of spatial information observed as an increase ...

This study assessed whether creatine could attenuate 3-nitropropionic acid (3NP)-induced neuropathological and behavioral abnormalities that are analogous to those observed in Huntington's disease (HD). Rats were fed diets containing either 1% creatine or normal rat chow for 2 weeks prior to the onset of 3NP administration, and for the duration ...

The present study was designed to characterize the possible roles of spinally located cholera toxin (CTX)- and pertussis toxin (PTX)-sensitive G-proteins in excitatory amino acids induced pain response. Intrathecal (i.t.) injection of glutamate (20 microg), N-methyl-D-aspartic acid (NMDA; 60 ng), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA; 13 ng), and kainic acid (12 ng) ...

Primary spinal cord trauma can trigger a cascade of secondary processes leading to delayed and amplified injury to spinal cord neurons. Release of fatty acids, in particular arachidonic acid, from cell membranes is believed to contribute significantly to these events. Mechanisms of fatty acid-induced injury to spinal cord neurons may ...

We studied the temporal changes in expression of neuronal nitric oxide (NO) synthase (nNOS) mRNA in the hippocampus of rats treated with kainic acid by use of in situ hybridization technique. Intraperitoneal injection of 10 mg kg-1 kainic acid decreased expression of nNOS mRNAs in the dentate gyrus and CA3 ...

Fresh rat brain slices were incubated with [18F]2-fluoro-2-deoxy-D-glucose ([18F]FDG) in oxygenated Krebs-Ringer solution at 36 degrees C, and serial two-dimensional time-resolved images of [18F]FDG uptake in the slices were obtained on imaging plates. The fractional rate constant of [18F]FDG (proportional to the cerebral glucose metabolic rate) from pre-loading of ischemia ...

Global hypoxia preconditioning provides neuroprotection against a subsequent, normally damaging challenge. While the mechanistic pathways are unknown, changes in the expression of stress-related proteins are implicated. Hypoxia preconditioning attenuates the brain edema and neuropathology associated with kainic acid-induced status epilepticus in a protein synthesis-dependent manner when a kainic acid challenge ...

Of the twenty amino acids in the mammalian body, only serine and aspartate occur in D-configuration as well as L-configuration in significant amount. D-serine is selectively concentrated in the brain, localized to protoplasmic astrocytes that ensheath synapses and distributed similarly to N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. D-serine has been ...

Citrate, a normal constituent of cellular metabolism, in a binary mixture with an amino acid enhanced asynchronous olfactory receptor responses in the channel catfish, Ictalurus punctatus. In addition, high concentrations of either citrate (> or =3 mM) alone or an amino acid (> or =0.1 mM) in a binary mixture ...

Kainic acid produces a persistent hyperalgesia when injected intraperitoneally (i.p.) in the rat or mouse. At higher doses than those needed to influence nociception, kainic acid induces seizures and translocation of histologically reactive zinc in the hippocampus. We tested the hypothesis that zinc, localized in a population of small diameter ...

The aim of this study was to determine in vivo which extracellular levels of kynurenic acid (KYNA) are required to control excessive NMDA receptor activation in the rat cortex. As excitotoxicity is coupled to marked ion movements, local depolarisations induced by perfusion of NMDA or quinolinic acid (QUIN) through microdialysis ...

Manipulation of the kynurenine pathway of tryptophan metabolism has yielded a plethora of agents that are now being developed as neuroprotectants and anticonvulsants. This pathway is involved in the production of the excitotoxin quinolinic acid and the neuroprotectant kynurenic acid. Approaches used in the development of therapeutic agents include production ...

We have synthesized D-glucose or D-galactose esters of 7-chlorokynurenic acid (7ClKynA) as prodrugs to facilitate the transport of 7ClKynA across the blood-brain barrier. Intraperitoneal (i.p.) administration of either 7ClKynA-D-glucopyranos-6'-ylester (7ClKynA/Glu6) or 7ClKynA-D-glucopyranos-3'-yl ester (7ClKynA/Glu3) was protective against seizures induced by N-methyl-D-aspartate (NMDA) in mice, with the former drug showing the ...

The role of oxidative stress in seizure-induced brain injury was investigated in a kainic acid model of experimental epilepsy. Kainic acid (12.5 mg/kg) or saline was injected intraperitoneally into 12-week-old male Fischer 344 rats and sacrificed by decapitation at 4 and 24 h after injection. Markers of oxidative stress including ...

We have previously reported that spontaneous release of excitatory amino acids (aspartate and glutamate) show remarkable circadian rhythms in the organotypic slice culture of rat suprachiasmatic nucleus (SCN). Here we showed effects of extracellular Ca(2+) removal and of L-trans-pyrrolidine-2,4-dicarboxylic acid, a glutamate/aspartate uptake inhibitor on the circadian release of excitatory ...

Synaptic activation of metabotropic glutamate receptors (mGluRs) in the locus coeruleus (LC) was investigated in adult rat brain slice preparations. Evoked excitatory postsynaptic potentials (EPSPs) resulting from stimulation of LC afferents were measured with current clamp from intracellularly recorded LC neurons. In this preparation, mGluR agonists (+/-)-1-aminocyclopentane-trans-1, 3-dicarboxylic acid (t-ACPD) ...

Regioisomeric 3-carboxyisoxazolinyl prolines (CIP-A and CIP-B) and 3-hydroxyisoxazolinyl prolines [(+/-)-8 and (+/-)-9] were synthesized and assayed for glutamate receptor activity. CIP-A [(+/-)-6] showed a convulsant activity evaluated in vivo on DBA/2 mice, higher than AMPA and similar to kainic acid. The eutomer of CIP-A [CIP-AS, (-)-6], obtained from (S)-3,4-didehydroproline, evidenced ...

Strokes (intracranial thomboses or haemorrhaging) cause death and disability, but effective treatments are lacking. The metabolism of tryptophan leads to the generation of quinolinic acid, an agonist potentially neurotoxic at glutamate receptors, and kynurenic acid, an antagonist at the same population of receptors. The commercial development of the kynurenine pathway ...

The hypothesis that release of adenosine following spinal cord injury (SCI) may provide neuroprotective feedback is explored. Consistent with this hypothesis, substantial release of adenosine, estimated to reach 100 microM in the extracellular space, was detected by microdialysis sampling immediately following contusion SCI. There is also considerable release of excitatory ...

Effects of comenic and meconic acids on cultured dorsal root ganglion cells were investigated by the whole-cell patch clamp technique. The acids, having a well-known antiinflammatory and antibacterial action, decreased effective charge transfer in the activation gating system of TTX-resistant (slow) sodium channels in a dose-dependent manner. The effects were ...

It is hypothesized that the locus coeruleus-noradrenergic system controls compensatory and repair mechanisms in the CNS, and that its dysfunction is a critical factor in the progression of central neurodegenerative diseases. Pharmacological activation of locus coeruleus neurons can be achieved with alpha2-adrenoceptor antagonists, and such compounds are protective in vivo ...

Glutaryl-CoA dehydrogenase deficiency (GDD), which is one of the most frequent organic acid disorders, is characterized by a specific age- and regional-dependent neuropathology. We hypothesized that the distinct brain damage in GDD could be caused by the main pathologic metabolites, the organic acids glutaric (GA) and 3-hydroxyglutaric (3-OH-GA) acids, through ...