Neuropeptide Y (NPY), a 36 amino-acid member of the pancreatic polypeptide family, has received considerable attention in recent years as an endogenous modulator of epileptic activity. Prominently expressed in brain regions involved in seizure generation and propagation, NPY can exert powerful effects on synaptic transmission. Here, we discuss the anti-epileptic ...

Mice with targeted deletion of the GABA catabolic enzyme succinic semialdehyde dehydrogenase (SSADH) manifest lethal tonic-clonic seizures, amenable to pharmacologic rescue, at 3-4 weeks of life. In the current report, we characterized amino acid profiles in SSADH(-/-) brain utilizing whole brain and regional extracts (frontal and parietal cortex, hippocampus, and ...

Vasopressinergic hypothalamic magnocellular neurosecretory cells fire in phasic bursts. Burst initiation involves summation of postsynaptic potentials to generate action potentials. Action potentials are each followed by a nonsynaptic depolarizing after-potential that summates temporally to generate a plateau potential and so sustain activity throughout the burst. It is unknown whether this ...

We previously identified a novel endogenous substance, serofendic acid, from a lipophilic extract of fetal calf serum. Serofendic acid protects cultured cortical neurons against the cytotoxicity of glutamate and nitric oxide. Here, we reported the protective effect of serofendic acid on reactive oxygen species-induced oxidative stress using primary rat striatal ...

Ursolic acid is the major component of extracts of the Chinese herb, Souyang. This study determines whether and how ursolic acid protects against kainate-induced excitotoxicity in rat hippocampus. Primary neuronal cultures of cells isolated from the hippocampi of 7-day-old rats were treated with 150 microM kainate. After 2 h of ...

The goals of the present study were to determine if ibotenic acid lesions of the dorsal hippocampus (dHPC) or of mammillary body (MB) of the hypothalamus would induce similar contextual conditioning deficit in a fear-conditioning paradigm, previously developed in mice [Eur. J. Neurosci. 12 (2000) 2575]. Results showed that ibotenic ...

The concentrations of glutamic and aspartic acids were measured in the dialysate obtained with vertical microdialysis probes implanted into the paraventricular nucleus of the hypothalamus of sexually potent male rats during sexual activity. Animals showed noncontact erections when put in the presence of, and copulated with, a receptive (ovarietomized oestrogen- ...

Amnesic shellfish poisoning (ASP) is caused by consumption of shellfish that have accumulated domoic acid, a neurotoxin produced by some strains of phytoplankton. The neurotoxic properties of domoic acid result in neuronal degeneration and necrosis in specific regions of the hippocampus. A serious outbreak of ASP occurred in Canada in ...

Quisqualic acid induces sensitisation of neurones to depolarisation by analogues of 2-amino-4-phosphonobutyric acid (AP4), phenylglycine, and homoibotenic acid (HIBO). Thus, after administration of quisqualate these analogues become active at concentrations at which they are otherwise inactive. The mechanisms behind quisqualate-induced sensitisation are poorly understood and have not previously been quantified ...

In the present communication, the dynamic release of amino acid (AA) transmitters induced by valproate (VPA) in pentylenetetrazol (PTZ)-kindled freely moving rats hippocampus has been determined. The results showed that glutamate and aspartate release were significantly increased during the seizure/interical periods, and markedly decreased after the application of 200mg/kg valproate. ...

The present study attempts to highlight the principles by which peripheral olfactory information of across- and within-class odorant signals is transformed into bulbar neuron responses. For this purpose, we performed electro-olfactogram cross-adaptation and mixture experiments as well as single unit recording of olfactory bulb neurons using amino acid, bile acid ...

The role of fatty acids (FA) and their impact on nervous system activity and immune function has attracted much attention. The interest extends beyond a basic understanding of the potential role exerted by FA on the neuronal membrane and its properties, to the implications and clinical significance for many neurological ...

We have investigated the role of inflammation in the excitotoxicity induced by overstimulation of glutamate receptors using kainic acid, an important tool for studying functions related to excitatory amino acid transmission and for producing neuronal death, especially in areas CA1 and CA3 of the hippocampus. We hypothesised that by inhibiting ...

Glutaryl-CoA dehydrogenase deficiency is an inherited organic aciduria with predominantly neurological presentation. Biochemically, it is characterized by an accumulation and enhanced urinary excretion of two key organic acids, glutaric acid and 3-hydroxyglutaric acid. If untreated, acute striatal degeneration is often precipitated by febrile illnesses during a vulnerable period of brain ...

Glutaric aciduria type I is an inborn error of organic acid metabolism that demonstrates a particular temporal vulnerability (acute encephalopathic episodes in infancy) and a spatial vulnerability (acute striatal necrosis, focused on the putamen). Excitotoxic mechanisms involving 3-hydroxyglutaric acid as the major neurotoxin have been suggested. This paper proposes a ...

Kynurenic acid (KYNA) is the only known endogenous N-methyl-D-aspartate (NMDA) receptor inhibitor and might therefore come into consideration as a therapeutic agent in certain neurobiological disorders. However, its use as a neuroprotective compound is practically excluded because KYNA does not readily cross the blood-brain barrier (BBB). We recently synthetized a ...

BACKGROUND: Glutamate is the principal excitatory neurotransmitter in the brain. Injury to the brain can cause an ionic imbalance in cerebral tissue, creating an excitotoxic cascade involving glutamate and other excitatory amino acids, that leads to neuronal death in the tissue surrounding the original injury site. Research has centred around ...

Kynurenines are endogenous metabolites of tryptophan, which are studied extensively in vertebrates with respect to their etiological role in the pathology of various neurodegenerative disorders. In insects, metabolites of the kynurenic pathway are present in peak concentrations in the hemolymph of holometabolic species during pupation and just before eclosion. Unlike ...

The ovarian hormone 17beta-estradiol (E2) is neuroprotective in animal models of neurodegenerative diseases. Some studies suggest that the neuroprotective effects of 17beta-estradiol are a consequence of its antioxidant activity that depend on the hydroxyl group in the C3 position of the A ring. As in other tissues, 17beta-estradiol is metabolized ...

The 17 amino acid peptide nociceptin has been implicated in pain modulation in the central nervous system. The effects of bath applied nociceptin, and some analogues of nociceptin, upon spontaneous lumbar dorsal root activity have been investigated in an isolated preparation of rat spinal cord. Nociceptin was found to reversibly ...

To investigate central respiratory control mechanisms in channel catfish, microinjections of kainic acid (causing chemical lesion of neurons) or kynurenic acid (an antagonist of N-methyl-D-aspartate (NMDA), kainate and alpha-amino-3-OH-5-methyl-4-isooxazole-propionic-acid (AMPA) receptors) were made into the general visceral nucleus (nGV) of the medulla in anaesthetised spontaneously breathing animals. Kainic acid abolished ...

Several studies have demonstrated that the nonselective opioid receptor antagonist naloxone produces a paradoxical antinociception in the formalin test. The opioid system is related to the serotonergic system for producing antinociception at the spinal level. Here we also asked whether systemic (i.p.) and intrathecal (i.t.) administrations of a nonselective serotonergic ...

The brain microdialysis technique has been used to examine the in vivo effects of the neurotoxin domoic acid (an ionotropic glutamate receptor agonist) on dopamine (DA) release in the striatum of conscious and freely moving rats. Local application of domoic acid (500 microM) through the microdialysis probe produced an increase ...

We have previously reported that a novel neuroprotective substance named serofendic acid was purified and isolated from ether extract of fetal calf serum. In the present study, we investigated the effect of serofendic acid on acute neurotoxicity induced by L-glutamate (Glu) using primary cultures of rat cortical neurons. Exposure of ...

This study examined the nociceptive effects of the intrathecal administration of various doses of the following endogenous excitatory sulphur-containing amino acids (SAAs): L-cysteic acid (L-CA), L-cysteine sulfinic acid (L-CSA), L-homocysteic acid (L-HCA) and L-homocysteic sulfinic acid (L-HCSA). For a period of 10min, rats were observed for spontaneous nociceptive behaviours (SNBs), ...

L-Glutamic acid acts as the major excitatory neurotransmitter and, at the same time, represents a potential neurotoxin for the mammalian central nervous system (CNS). The termination of excitatory transmission and the maintenance of physiologic levels of extracellular glutamate, which is necessary to prevent excitotoxicity, are prominently mediated by a family ...

OBJECTIVES: To investigate whether the excitatory amino acid receptor agonists can activate the paraventricular nucleus of the hypothalamus (PVN) and induce penile erections in the rat. METHODS: Male adult Sprague-Dawley rats were used. A 26-gauge needle was inserted into the corpus cavernosum to monitor the intracavernous pressure (ICP) simultaneously with ...

Kainic acid induces excitotoxicity and nerve cell degeneration in vulnerable regions of rat brain, most markedly in hippocampus and amygdala. Part of the cell death following kainic acid is apoptotic as shown by caspase 3 activation and chromatin condensation. Here we have studied the regulation of pro- and anti-apoptotic proteins ...

Glutamate excitotoxicity has been implicated in the pathophysiology of epilepsy. Systemic injection of kainic acid (KA) in the rat produces an animal model of human temporal lobe epilepsy. We examined the temporal expression of the sodium-dependent neuronal glutamate transporter, excitatory amino acid carrier 1 (EAAC1), in KA-induced rat epilepsy. As ...

A recent study describing two epileptic patients with brain cysts has suggested that elevated concentrations of excitatory amino acids in cysts may play a role in induction and maintenance of epileptogenesis [Epilepsy Res. 28 (1997) 245]. Here, we report that only in 3 out of 22 patients with brain cysts ...

The effects of alpha-ketoglutarate and oxaloacetate on brain mitochondrial DNA (mtDNA) damage and seizures induced by kainic acid were examined both in vivo and in vitro. An intraperitoneal (ip) injection of kainic acid (45 mg/kg) produced broad-spectrum limbic and severe sustained seizures in all of the treated mice. The seizures ...

Tryptophan is metabolised primarily along the kynurenine pathway, of which two components are now known to have marked effects on neurons in the central nervous system. Quinolinic acid is an agonist at the population of glutamate receptors which are sensitive to N-methyl-D-aspartate (NMDA), and kynurenic acid is an antagonist at ...

Whether odorants are transduced by only one or more than one second messenger has been a long-standing question in olfactory research. In a previous study we started to address this question mainly by using calcium imaging in the olfactory bulb. Here, we present direct evidence for our earlier conclusions using ...

The bioassay-guided fractionation of the water-soluble extract of the marine sponge Cribrochalina olemda collected in Palau resulted in the isolation of a new amino acid cribronic acid (1): (2S,4R,5R)-5-hydroxy-4-sulfooxypiperidine-2-carboxylic acid. However, aqueous extracts of Stylotella aurantium and Axinella carteri collected in Yap State, Micronesia, afforded a known N-methyl-d-aspartic acid (NMDA)-type ...

BACKGROUND: Mesial temporal lobe epilepsy (mTLE) is characterized by hippocampal atrophy, decreased N-acetyl-aspartate, and a low N-acetyl-aspartate/total creatine ratio, often attributed to neuron loss and gliosis. Qualitative studies reported that N-acetyl-aspartate content was significantly lower in hippocampal sclerosis. OBJECTIVE: It was proposed to measure the effects of neuron loss and ...

On the basis of structural studies, chloro-homoibotenic acid (Cl-HIBO) was designed and synthesized. Cl-HIBO was characterized in binding and electrophysiology experiments on native and cloned subtypes of GluRs. Electrophysiological selectivities ranged from 275 to 1600 for GluR1/2 over GluR3/4. The potent AMPA receptor activity was strongly desensitizing and the neurotoxicity ...

Bombycis corpus (BC) or Bombyx Batryticatus, a batryticated silkworm and white-stiff silkworm, is a drug consisting of the dried larva of silkworm, Mobyz mori L., dead and stiffened due to the infection of Beauveria (Bals.) Vuill. In a previous paper (Kim et al., Pharmacol. Res., 43, 12-16, 2001), BC was ...

In vitro and in vivo brain slice techniques were used to examine phencyclidine (PCP) effects on the lateral propagation of epileptiform field potentials (EFP) across adjacent areas of rat frontal neocortex. Epileptiform activity was induced by perfusing slices with Mg 2+-free artificial cerebrospinal fluid. Simultaneous field potential recordings of EFP ...

The accumulated data indicate that massively released excitatory amino acids play a major role in mediating the acute ischemic neuronal degeneration. Kynurenic acid (KYNA), the endogenous glutamate receptor antagonist, displaying a particularly high affinity for the glycine-site of N-methyl-D-aspartate (NMDA) receptor, was shown to ameliorate ischemic brain damage and its ...

Acute, subacute and chronic neurotoxicity have been observed after the administration of high-dose and/or intrathecal methotrexate (MTX). Acute toxicity is usually transient without permanent damage. Subacute and chronic toxicity are associated with changes in the brain and/or the spinal cord which may be progressive and even lead to coma and ...

The nucleus isthmi (NI) is a mesencephalic structure of the amphibian brain that has been reported to participate in CO(2) chemoreception and in the ventilatory response to hypoxia. In the present study, we assessed the role of glutamatergic transmission inside the NI on the hypoxic and hypercarbic drive to breathing. ...

Calsenilin is a neuronal calcium binding protein that may function in calcium signaling and cell death. Kainic acid, an analog of the excitatory amino acid L-glutamate, produced excitotoxic cell death and induced the pathophysiology of status epilepticus. The expression of calsenilin was investigated in the mouse brain after kainic acid-induced ...

We have examined the neuroprotective efficacy of the mitochondrial uncoupler 2,4-dinitrophenol (DNP) in animals receiving striatal injections of the neurotoxin quinolinic acid. Animals administered DNP either 1 h before or 3 h following QA infusion developed lesions that were 25% smaller than control animals. Animals treated with the DNP analogue ...

Kainic acid induces seizures and neurotoxicity in rats, produces changes in brain serotonin (5-HT), dopamine and noradrenaline metabolites among other changes in neurotransmitters. In this work, we investigated the changes in 5-HT turnover in brain regions from 84 rats intraperitoneally injected with kainic acid and a specific behavioural change, the ...

The design and synthesis of conformationally restricted analogues of alpha-amino acids is an often used strategy in medicinal chemistry research. Here we present the rational design, synthesis, and pharmacological evaluation of 2-azanorbornane-3-exo,5-endo-dicarboxylic acid (1), a novel conformationally restricted (S)-glutamic acid (Glu) analogue intended as a mimic of the folded Glu ...

The effects of ganglioside GT1b or melatonin on damage to brain mitochondrial DNA (mtDNA) and seizures induced by kainic acid were investigated both in vivo and in vitro. An intraperitoneal (i.p.) injection of kainic acid (45 mg/kg) produced broad-spectrum limbic and severe sustained seizures in all of the treated mice. ...

The anticonvulsant activities of some 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionic acid (AMPA)/kainate receptor antagonists, noncompetitive (2,3-benzodiazepines) and a competitive 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)-quinoxaline (NBQX), were compared in different experimental seizure models. In particular, compounds were evaluated against audiogenic seizure in DBA/2 mice, maximal electroshock seizure (MES) test and various chemoconvulsant models; both groups showed a protective action ...

Historically, 3,4-dihydroxyphenylalanine (DOPA) has been believed to be an inert amino acid that alleviates the symptoms of Parkinson's disease by its conversion to dopamine via the enzyme aromatic L-amino acid decarboxylase. In contrast to this generally accepted idea, we propose that DOPA itself is a neurotransmitter and/or neuromodulator, in addition ...

The effects of dextromethorphan (DM), and its major metabolite dextrorphan (DX) on kainic acid-induced seizures in mice were examined. Intracerebroventricular DM or DX (5 or 10 microg/0.5 microl) pretreatment significantly attenuated seizures induced by kainic acid (0.07 microg/0.07 microl) in a dose-related manner. DM or DX pretreatment significantly attenuated kainic ...

Unilateral microinjection of Angiotensin-(1-7)[Ang-(1-7)] into the rostral ventrolateral medulla (RVLM) of anesthetized rats caused an increase in mean arterial pressure (MAP) accompanied by an increased release of excitatory amino acid (EAA) glutamate. In contrast, microinjection of Ang779, a selective antagonist of Ang-(1-7) receptor, into the RVLM caused a decrease in ...