Several differences exist between quinolinic acid and N-methyl-D-aspartate (NMDA) in the potency and pharmacology of their neurotoxic actions in the brain, suggesting that quinolinic acid may act by mechanisms additional to the activation of NMDA receptors, possibly involving lipid peroxidation. In the present review, studies are considered which have attempted ...

We recorded simultaneously the electrophysiological responses of the olfactory organ [the electroolfactogram (EOG)] and action potential activity of single olfactory receptor neurons (ORNs) to amino acid stimuli in the brown bullhead catfish, Ameiurus nebulosus. To determine whether the amplitude of the EOG depends upon the number of responding ORNs, we ...

A number of data concerning the central action of mitochondrial toxins, substances impairing mitochondrial synthesis of ATP and thus compromising cellular energy status, has emerged within last years. 3-Nitropropionic acid (3-NPA) is an irreversible inhibitor of succinate dehydrogenase and mitochondrial complex II. The experimental administration of 3-NPA may lead to ...

Two anionic fluorescein derivatives can be used for the simple and definitive localization of neuronal degeneration in brain tissue sections. Initial work on the first generation fluorochrome, Fluoro-Jade, demonstrated the utility of this compound for the detection of neuronal degeneration induced by a variety of well-characterized neurotoxicants, including kainic acid, ...

Using the technique of intracellular recording in in vitro brain slice preparations, we examined the effects produced by repeated administration of the antipsychotic drugs clozapine, olanzapine and haloperidol, on N-methyl-D-aspartic acid-induced responses in pyramidal cells of the rat medial prefrontal cortex. Rats were anesthetized and decapitated 24h after the conclusion ...

Poly(ADP-ribose) polymerase (PARP) is activated in glutamate-induced toxicity of neurons in culture (Cosi et al., 1994). Since injection of the excitatory amino acid, kainic acid (KA) into the rat striatum induces a delayed neuronal death, the effects of this in vivo excitotoxin lesioning procedure on striatal PARP activity was investigated. ...

Aspirin (acetylsalicylic acid), and its main metabolite sodium salicylate, have been shown to protect neurons from excitotoxic cell death in vitro. The objective of our study was to investigate the possible neuroprotective effects of sodium salicylate in vivo in rats with kainic acid-induced seizures, a model for temporal lobe epilepsy ...

The role of astrocytes in the production of the neurotoxin quinolinic acid (QUIN) and other products of the kynurenine pathway (KP) is controversial. Using cytokine-stimulated human astrocytes, we assayed key enzymes and products of the KP. We found that astrocytes lack kynurenine-hydroxylase so that large amounts of kynurenine (KYN) and ...

This study was aimed at investigating the effects of lamotrigine (LTG) on electrically evoked field excitatory postsynaptic potentials (fEPSP) and population spikes in the CA1 hippocampal region of guinea pigs. The concentration response curves showed different actions of LTG on fEPSP and on population spikes. The data are in contrast ...

The influence of nitric oxide synthase (NOS) activity on the KCl-evoked amino acid concentrations was investigated by in vivo microdialysis in the striatum in a rat model of excitotoxic lesion. Basal microdialysate levels of amino acids decreased during the quinolinic acid-induced neurodegeneration process, except for glutamine that increased initially and ...

3-Nitropropionic acid (NPA), an inhibitor of succinate dehydrogenase, is dietary neurotoxin. It is not known if neurons and astrocytes differ in their vulnerability to NPA, therefore, we investigated its toxicity in primary cultures of cerebellar granule cells and astrocytes. NPA inhibited succinate dehydrogenase and tricarboxylic acid cycle activity to the ...

Research within the past decade has provided compelling evidence that anaesthetics can act directly as allosteric modulators of transmitter-gated ion channels. Recent comparative studies of the effects of general anaesthetics across a structurally homologous family of inhibitory amino acid receptors that includes mammalian GABAA, glycine and Drosophila RDL GABA receptors ...

Little is known about the differences in the distributions of inhibitory and excitatory synapses in the dendritic tree of single motoneurons in the brainstem and spinal cord. In this study, the distribution of gamma-aminobutyric acid (GABA)-, glycine-, and glutamate-like immunoreactivity in axon terminals on dendrites of cat masseter alpha-motoneurons, stained ...

Thioredoxin (TRX) is a small, multifunctional protein with a redox-active site and multiple biological functions that include reducing activity for reactive oxygen intermediates. We assayed TRX by immunohistochemical methods in the rat brain after intraperitoneal injection of 3-nitropropionic acid (3-NP), an irreversible inhibitor of succinate dehydrogenase. Systemic administration of 3-NP ...

Organotypic rat hippocampal slice cultures were used to study the role of excitatory amino acid transporters (EAATs) in kainate-induced cell death. Expression of the neuronal (EAAT3) or glial (EAAT2) transporters was inhibited with antisense phosphothioate oligonucleotides, and cytotoxicity was assessed with propidium iodide uptake. In control cultures, a concentration of ...

Nociceptive primary afferent C-fibers express a subset of glutamate receptors that are sensitive to kainic acid. Thus, we tested the possibility that activation of these receptors alters nociception. Intraperitoneal (i.p.) injection of kainic acid induced a persistent thermal hyperalgesia, when tested using the hot plate (mice) and tail flick (mice ...

Depolarization-induced suppression of inhibition (DSI) is a process whereby brief approximately 1-s depolarization to the postsynaptic membrane of hippocampal CA1 pyramidal cells results in a transient suppression of GABA(A)ergic synaptic transmission. DSI is triggered by a postsynaptic rise in [Ca(2+)](in) and yet is expressed presynaptically, which implies that a retrograde ...

1 Losigamone is a novel anticonvulsant undergoing phase III clinical trials in patients with partial and secondary generalized seizures. This study investigated the effects of the S(+)- and R(-)- enantiomers of losigamone on endogenous amino acid release from BALB/c mouse cortical slices, spontaneous depolarizations in the cortical wedge preparation of ...

Kynurenic acid (KYNA) is an antagonist of (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptors and it blocks the glycine site of the NMDA receptor preferentially (IC50 = 7.9 microM). KYNA is produced endogenously by transamination of its precursor L-kynurenine (L-KYN). We tested the hypothesis that effects of endogenous, de novo ...

Release of amino acids, particularly the neurotoxin glutamate, in and around the site of an experimental spinal cord injury was characterized over time by microdialysis. Increases in amino acid concentrations caused by injury decline steeply and then slowly over distance from the impact area, becoming undetectable beyond about 5 mm ...

The ability of a broad spectrum glutamatergic receptor antagonist, kynurenic acid (1 and 5 mM) to attenuate release of excitant and other amino acids from the ischemic cerebral cortex was examined in a four vessel occlusion rat model. Kynurenic acid, administered topically onto the cortex in artificial cerebrospinal fluid using ...

(RS)-2-Amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA), an analogue of (RS)-2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid (AMPA). has previously been shown to be a relatively weak AMPA receptor agonist and a very potent agonist at the GluR5 subtype of kainic acid-preferring (S)-glutamic acid ((S)-Glu) receptors. We report here the separation of (+)- and (-)-ATPA, obtained at high enantiomeric ...

The effects of intracerebroventricular administration of procaine 2 mumol on ischaemic release of neurotransmitter amino acids in the gerbil hippocampal CAI region were investigated using a microdialysis-high-performance liquid chromatography procedure. Histological outcome was examined by comparing delayed neuronal death between animals treated with procaine before ischaemia and animals treated after ...

Little is known concerning the changes of amino acid composition in different regions of the spinal cord in patients with amyotrophic lateral sclerosis (ALS). We performed quantitative amino acid analyses in the posterior funiculus, the lateral corticospinal tract, and the anterior horn of cervical enlargement of the spinal cord from ...

Spinal cord trauma can cause a marked release of free fatty acids, in particular, arachidonic acid (AA), from cell membranes. Free fatty acids, and AA by itself, may lead to secondary damage to spinal cord neurons. To study this hypothesis, cultured spinal cord neurons were exposed to increasing concentrations of ...

Previous studies have shown that the striatum expresses very low levels of Na+/Cl(-)-dependent "orphan" transporter Rxt1 transcripts but contains high levels of protein. This study investigated the origin of Rxt1 expression in rat striatum. Striatal Rxt1 contents assessed by immunocytochemistry or western blotting were found to be significantly reduced after ...

The associative avian forebrain region medio-rostral neostriatum/hyperstriatum ventrale (MNH) is involved in auditory filial imprinting and may be considered the avian analogue of the mammalian prefrontal cortex. In search of the neurochemical and physiological mechanisms which play a role in this learning process, we introduced microdialysis and a combined microdialysis/electrophysiological ...

An understanding of the role of reactive glia in the neurodegenerative/regenerative process requires a knowledge of the molecules synthesised by these cells following trauma. We investigated the cellular localisation of lipocortin-1 (LC-1), a putative neuroprotective agent, in cryostat sections of normal and kainic acid lesioned rat cerebellum. In the normal ...

The scrapie prion protein (PrP(Sc)) has been shown to induce apoptosis of rat cortical neurons in vitro. Here we demonstrate that the toxic effect displayed by PrP(Sc) can be blocked by sulfated colominic acid (polymer of N-acetylneuraminic acid). This compound acts neuroprotectively at a concentration of > or = 0.3 ...

OBJECT: Symptoms from Parkinson's disease improve after surgical ablation of the medial globus pallidus (GPm). Although, in theory, selective chemical ablation of neurons in the GPm could preserve vital structures jeopardized by surgery, the potential of this approach is limited when using traditional techniques of drug delivery. The authors examined ...

The lectin concanavalin A (ConA) when applied to the olfactory mucosa (OM) of frog and rat, is reported to partially inhibit electro-olfactogram (EOG) responses to fatty acid odours. Control odours like isoamyl acetate were not affected. We have now studied in the frog whether this treatment affects the corresponding olfactory ...

OBJECTIVE: This laboratory has demonstrated that lipid-coated microbubbles (LCMs) effectively aggregate and deliver chemotherapeutic drugs into rat brain tumor cells and antigliosis agents into maturing rat brain injury sites. In this study, we report the affinity of tail vein-injected LCMs to the injured rat spinal cord by a compressive lesion ...

Sensory neurons that innervate the heart sense ischemia and mediate angina. To use patch-clamp methods to study ion channels on these cells, we fluorescently labeled cardiac sensory neurons (CSNs) in rats so that they could later be identified in dissociated primary culture of either nodose or dorsal root ganglia (DRG). ...

The role of the glutamatergic system in the convulsant and proconvulsant action of a mitochondrial toxin, 3-nitropropionic acid, was studied in mice. The occurrence of 3-nitropropionic acid-induced seizures was inhibited by the alpha-amino-2,3-dihydro-5-methyl-3-oxo-isoxazole-propionate (AMPA)/kainate receptor antagonists, 6-nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-dione disodium (NBQX) and 1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine HCI (GYKI 52466), with ED50 of 14.1 (7.9-25.2) and ...

Although, area postrema (AP) as been implicated in the regulation of cardiovascular function, there is no consensus regarding the type of responses elicited by stimulation of this brain structure. Microinjections (50 nl) of smaller concentrations of excitatory amino acid receptor agonists (e.g., NMDA, KA and trans-ACPD, 10 microM each) into ...

The purpose of the present study was to determine whether the motor impairment (myorelaxation/ataxia) induced by excitatory amino acid receptor antagonists was exaggerated by pretreatment with ethanol. The results were compared with those of gamma-aminobutyric acid(A) (GABA(A)) receptor positive modulators alone and in combination with ethanol. The excitatory amino acid ...

Quinolinic acid (QUIN) displaced binding of agonist and antagonist ligands for the N-methyl-D-aspartate (NMDA) receptor in rat brain synaptic membranes. Both QUIN and glutamic acid (GLU) potentiated binding of [3H]dizocilpine (MK-801) in the presence of glycine (GLY) alone, whereas the potentiation by QUIN was in a bell-shaped fashion in contrast ...

Endogenous excitotoxins have been implicated in degeneration of nigral dopaminergic neurons in Parkinson's disease. It may be possible to reduce neurodegeneration by blocking the effects of these endogenous agents. The present study shows that contralateral turning seen following quinolinic acid-induced lesions of the nigrostriatal dopaminergic pathway was reversed by a ...

The majority of human spinal cord injuries involve gray matter loss from the cervical or lumbar enlargements. However, the deficits that arise from gray matter damage are largely masked by the severe deficits due to associated white matter damage. We have developed a model to examine gray matter-specific deficits and ...

The effects of drugs affecting GABA and glutamic acid receptors on theophylline-induced seizures were investigated in mice. Theophylline elicited tonic seizures in mice in a dose dependent manner. Muscimol, DABA and AOAA significantly prolonged the onset and significantly decreased the incidence of theophylline-induced seizures. Baclofen significantly delayed the onset of ...

To investigate the modes of action of potential neurotransmitters for cardiovascular control, amino acids and an antagonist were injected intracisternally into conscious rats. Blood pressure and superior mesenteric flow were measured with cannulae and electromagnetic flow probes that had been implanted in a previous operation under pentobarbitone anaesthesia. L-Proline, L-glutamate ...

This study was designed to examine the role of 2-oxoacids in the enzymatic transamination of L-kynurenine to the excitatory amino acid receptor antagonist, kynurenate, in the rat brain. In brain tissue slices incubated in Krebs-Ringer buffer with a physiological concentration of L-kynurenine, pyruvate, and several other straight- and branched-chain 2-oxoacids, ...

We investigated changes in numbers of nitric-oxide-producing cells in the hippocampal formation, striatum, and temporal cortex of mice 24 h after intraperitoneal administration of kainic acid (5, 10, 15, and 20 mg/kg) or domoic acid (1, 2, and 4 mg/kg). Nitric-oxide-producing cells were demonstrated histochemically by staining for nicotinamide adenine ...

The present study was undertaken to explore the effects of central serotonin receptor activation on the expression of glial fibrillary acidic protein in the suprachiasmatic nucleus of Syrian hamsters. Immunoblot and immunohistochemical procedures were used to examine the effects of systemic application of the serotonin-1A and serotonin-7 receptor agonist, (+/-)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronaphthalene ...

Primary cultures of cerebral neurons of Sprague-Dawley rats increased cyclic GMP production in response to the stimulation of excitatory amino acids, including N-methyl-D-aspartate, quisqualate, kainate and (+/-)-1-aminocylopentane-trans-1,3-dicarboxylic acid. This increased cyclic GMP production was significantly inhibited by halothane or isoflurane at clinically relevant concentrations (0.5-2%). This inhibition was reversible by ...

In this study we evaluated the effect of baclofen on excitotoxic action of quinolinic acid in hippocampus following its prolonged systemic administration in rats. Male Wistar rats, weighing 200-220 g, were used in the study. Quinolinic acid and baclofen were administered alone or together. Quinolinic acid was administered intraperitoneally (i.p.) ...

Quinolinic acid, a metabolite of tryptophan in the kynurenine pathway, inhibited the 5-HT(2A/2C) direct agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino propane hydrochloride (DOI) induced head shakes in mice in a dose-dependent manner. This effect was observed 10 min after intracerebroventricular (i.c.v.) administration of 0.0625-1 microg/mouse. 3-Hydroxyanthranilic acid, which is the immediate stable precursor of ...

Neuronal death was produced in the CA1 and CA3 areas of the hippocampus, amygdala, and piriform and entorhinal cortices after intraperitioneal administration of kainic acid at convulsant doses to adult rats. To assess the involvement of members of the Bcl-2 family in cell death or survival, immunohistochemistry, western and northern ...

The phosphono amino acid, (RS)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl+ ++]propio nic acid (ATPO), is a structural hybrid between the NMDA antagonist (RS)-2-amino-7-phosphonoheptanoic acid (AP7) and the AMPA and GluR5 agonist, (RS)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA). ATPO has been resolved into (S)-ATPO and (R)-ATPO using chiral HPLC, and the absolute stereochemistry of the two enantiomers was established ...

Human ingestion of "chickling peas" from the plant Lathyrus sativus, which contains an excitatory amino acid, L-BOAA (L-beta-N-oxalylamino-L-alanine), leads to a progressive corticospinal neurodegenerative disorder, neurolathyrism. Exposure to L-BOAA, but not its optical enantiomer D-BOAA, causes mitochondrial dysfunction as evidenced by loss of complex I activity in vitro in male ...