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Excitatory Amino Acids (excitatory + amino_acids)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Effects of Acamprosate on Excitatory Amino Acids During Multiple Ethanol Withdrawal Periods

ALCOHOLISM, Issue 3 2003
Abdelkader Dahchour
Background: Our previous studies on the effects of acamprosate on enhanced locomotion during repeated withdrawals are now extended to the effects of acamprosate on excitatory amino acids in the hippocampus during repeated ethanol withdrawals. Methods: In this study, Wistar rats were made ethanol dependent by 4 weeks of vapor inhalation. After this first cycle of chronic ethanol treatment, rats underwent repeated and alternate cycles of 24 hr withdrawals and 1 week of chronic ethanol treatment. The microdialysis technique was used together with high-performance liquid chromatography and electrochemical detection to quantify different amino acids such as aspartate and glutamate. Results: An intraperitoneal administration of acamprosate (400 mg/kg) to naïve rats did not alter aspartate or glutamate levels compared with the saline groups. During the first cycle of ethanol withdrawal, the administration of acamprosate (400 mg/kg, intraperitoneally) 2 hr after the commencement of ethanol withdrawal decreased both aspartate and glutamate microdialysate levels when compared with their respective saline group. Acamprosate administration also significantly decreased glutamate levels during the third withdrawal compared with the saline group, whereas no changes were seen in aspartate levels. Conclusion: The results of this work demonstrate that acamprosate reduced the excitatory amino acid glutamate increase observed during repeated ethanol withdrawal. These effects of acamprosate may provide a protective mechanism against neurotoxicity by reducing excitatory amino acids, particularly glutamate. [source]

Glutamate enhances proliferation and neurogenesis in human neural progenitor cell cultures derived from the fetal cortex

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006
Masatoshi Suzuki
Abstract Excitatory amino acids such as glutamate play important roles in the central nervous system. We previously demonstrated that a neurosteroid, dehydroepiandrosterone (DHEA), has powerful effects on the cell proliferation of human neural progenitor cells (hNPC) derived from the fetal cortex, and this effect is modulated through NMDA receptor signaling. Here, we show that glutamate can significantly increase the proliferation rates of hNPC. The increased proliferation could be blocked by specific NMDA receptor antagonists, but not other glutamate antagonists for kainate,AMPA or metabotropic receptors. The NR1 subunit of the NMDA receptor was detectable in elongated bipolar or unipolar cells with small cell bodies. These NR1-positive cells were colocalized with GFAP immunoreactivity. Detection of the phosphorylation of cAMP response element-binding protein (pCREB) revealed that a subset of NR1-positive hNPC could respond to glutamate. Furthermore, we hypothesized that glutamate treatment may affect mainly the hNPC with a radial morphology and found that glutamate as well as DHEA selectively affected elongated hNPC; these elongated cells may be a type of radial glial cell. Finally we asked whether the glutamate-responsive hNPC had an increased potential for neurogenesis and found that glutamate-treated hNPC produced significantly more neurons following differentiation. Together these data suggest that glutamate stimulates the division of human progenitor cells with neurogenic potential. [source]

Evidence for vesicular glutamate transporter synapses onto gonadotropin-releasing hormone and other neurons in the rat medial preoptic area

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2003
J. Kiss
Abstract The medial preoptic area is a key structure in the control of reproduction. Several data suggest that excitatory amino acids are involved in the regulation of this function and the major site of this action is the medial preoptic region. Data concerning the neuromorphology of the glutamatergic innervation of the medial preoptic area are fragmentary. The present investigations were focused on: (i) the morphology of the vesicular glutamate transporter 1 (VGluT1)- and vesicular glutamate transporter 2 (VGluT2)-immunoreactive nerve terminals, which are considered to be specific to presumed glutamatergic neuronal elements, in the medial preoptic area of rat; and (ii) the relationship between these glutamate transporter-positive endings and the gonadotropin-releasing hormone (GnRH) neurons in the region. Single- and double-label immunocytochemistry was used at the light and electron microscopic level. There was a weak to moderate density of VGluT1- and a moderate to intense density of VGluT2-immunoreactive elements in the medial preoptic area. Electron microscopy revealed that both VGluT1- and VGluT2-immunoreactive boutons made asymmetric type synaptic contacts with unlabelled neurons. VGluT2-labelled, but not VGluT1-labelled, axon terminals established asymmetric synaptic contacts on GnRH-immunostained neurons, mainly on their dendrites. The present findings are the first electron microscopic examinations on the glutamatergic innervation of the rat medial preoptic area. They provide direct neuromorphological evidence for the existence of direct glutamatergic innervation of GnRH and other neurons in the rat medial preoptic area. [source]

The role of steroid hormones in the regulation of vasopressin and oxytocin release and mRNA expression in hypothalamo neurohypophysial explants from the rat

EXPERIMENTAL PHYSIOLOGY, Issue 2000
Celia D. Sladek
Vasopressin and oxytocin release from the neural lobe, and the vasopressin and oxytocin mRNA contents of the supraoptic and paraventricular nuclei are increased by hypertonicity of the extracellular fluid. The factors regulating these parameters can be conveniently studied in perifused explants of the hypothalamo-neurohypophysial system that include the supraoptic nucleus (but not the paraventricular nucleus) with its axonal projections to the neural lobe. Vasopressin and oxytocin release and the mRNA content of these explants respond appropriately to increases in the osmolality of the perifusate. This requires synaptic input from the region of the organum vasculosum of the lamina terminalis. Glutamate is a likely candidate for transmitting osmotic information from the organum vasculosum of the lamina terminalis to the magnocellular neurones, because agonists for excitatory amino acid receptors stimulate vasopressin and oxytocin release, and because increased vasopressin release and mRNA content induced in hypothalamo-neurohypophysial explants by a ramp increase in osmolality are blocked by antagonists of both NMDA (N -methyl-D-aspartate) and non-NMDA glutamate receptors. Osmotically stimulated vasopressin release is also blocked by testosterone, dihydrotestosterone, oestradiol and corticosterone. Both oestrogen and dihydrotestosterone block NMDA stimulation of vasopressin release, and in preliminary studies oestradiol blocked AMPA stimulation of vasopressin release. Thus, steroid inhibition of osmotically stimulated vasopressin secretion may reflect inhibition of mechanisms mediated by excitatory amino acids. Recent studies have demonstrated numerous mechanisms by which steroid hormones may impact upon neuronal function. Therefore, additional work is warranted to understand these effects of the steroid hormones on vasopressin and oxytocin secretion and to elucidate the potential contribution of these mechanisms to regulation of hormone release in vivo. [source]

Stress and hippocampal plasticity: implications for the pathophysiology of affective disorders

HUMAN PSYCHOPHARMACOLOGY: CLINICAL AND EXPERIMENTAL, Issue S1 2001
Bruce S. McEwen
Abstract The hippocampal formation, a structure involved in declarative, spatial and contextual memory, is a particularly sensitive and vulnerable brain region to stress and stress hormones. The hippocampus shows a considerable degree of structural plasticity in the adult brain. Stress suppresses neurogenesis of dentate gyrus granule neurons, and repeated stress causes atrophy of dendrites in the CA3 region. In addition, ovarian steroids regulate synapse formation during the estrous cycle of female rats. All three forms of structural remodeling of the hippocampus are mediated by hormones working in concert with excitatory amino acids (EAA) and N -methyl- D -aspartate (NMDA) receptors. EAA and NMDA receptors are also involved in neuronal death that is caused in pyramidal neurons by seizures and by ischemia and prolonged psychosocial stress. In the human hippocampus, magnetic resonance imaging studies have shown that there is a selective atrophy in recurrent depressive illness, accompanied by deficits in memory performance. Hippocampal atrophy may be a feature of affective disorders that is not treated by all medications. From a therapeutic standpoint, it is essential to distinguish between permanent damage and reversible atrophy in order to develop treatment strategies to either prevent or reverse deficits. In addition, remodeling of brain cells may occur in other brain regions. Possible treatments are discussed. Copyright © 2001 John Wiley & Sons, Ltd. [source]

Neuroendocrine mechanisms controlling female puberty: new approaches, new concepts

INTERNATIONAL JOURNAL OF ANDROLOGY, Issue 1 2006
Sergio R. Ojeda
Summary Sexual development and mature reproductive function are controlled by a handful of neurones that, located in the basal forebrain, produce the decapeptide luteinizing hormone releasing hormone (LHRH). LHRH is released into the portal system that connects the hypothalamus to the pituitary gland and act on the latter to stimulate the synthesis and release of gonadotrophin hormones. The pubertal activation of LHRH release requires coordinated changes in excitatory and inhibitory inputs to LHRH-secreting neurones. These inputs are provided by both transsynaptic and glia-to-neurone communication pathways. Using cellular and molecular approaches, in combination with transgenic animal models and high-throughput procedures for gene discovery, we are gaining new insight into the basic mechanisms underlying this dual control of LHRH secretion and, hence, the initiation of mammalian puberty. Our results suggest that the initiation of puberty requires reciprocal neurone-glia communication involving excitatory amino acids and growth factors, and the coordinated actions of a group of transcriptional regulators that appear to represent a higher level of control governing the pubertal process. [source]

Two conventional protein kinase C isoforms, , and ,I, are involved in the ATP-induced activation of volume-regulated anion channel and glutamate release in cultured astrocytes

JOURNAL OF NEUROCHEMISTRY, Issue 6 2008
Alena Rudkouskaya
Abstract Volume-regulated anion channels (VRACs) are activated by cell swelling and are permeable to inorganic and small organic anions, including the excitatory amino acids glutamate and aspartate. In astrocytes, ATP potently enhances VRAC activity and glutamate release via a P2Y receptor-dependent mechanism. Our previous pharmacological study identified protein kinase C (PKC) as a major signaling enzyme in VRAC regulation by ATP. However, conflicting results obtained with potent PKC blockers prompted us to re-evaluate the involvement of PKC in regulation of astrocytic VRACs by using small interfering RNA (siRNA) and pharmacological inhibitors that selectively target individual PKC isoforms. In primary rat astrocyte cultures, application of hypoosmotic medium (30% reduction in osmolarity) and 20 ,M ATP synergistically increased the release of excitatory amino acids, measured with a non-metabolized analog of l -glutamate, d -[3H]aspartate. Both Go6976, the selective inhibitor of Ca2+ -sensitive PKC,, ,I/II, and ,, and MP-20-28, a cell permeable pseudosubstrate inhibitory peptide of PKC, and ,I/II, reduced the effects of ATP on d -[3H]aspartate release by ,45,55%. Similar results were obtained with a mixture of siRNAs targeting rat PKC, and ,I. Surprisingly, down-regulation of individual , and ,I PKC isozymes by siRNA was completely ineffective. These data suggest that ATP regulates VRAC activity and volume-sensitive excitatory amino acid release via cooperative activation of PKC, and ,I. [source]

Species-specific chemosignals evoke delayed excitation of the vomeronasal amygdala in freely-moving female rats

JOURNAL OF NEUROCHEMISTRY, Issue 3 2006
Carla Mucignat-Caretta
Abstract Male rat chemosignals attract females and influence their reproductive status. Through the accessory olfactory bulb and its projection target, the posteromedial cortical nucleus of the amygdala (PMCo), species-specific chemosignals detected by the vomeronasal organ (VNO) may reach the hypothalamus. To test this hypothesis in vivo, behavioural activation and neurotransmitter release in the PMCo were simultaneously monitored in freely moving female oestrus rats exposed to either rat or mouse urinary stimuli, or to odorants. Plasma levels of the luteinizing hormone were subsequently monitored. All stimuli induced an immediate behavioural activation, but only species-specific chemosignals led to a delayed behavioural activation. This biphasic behavioural activation was accompanied by a VNO-mediated release of the excitatory amino acids, aspartate and glutamate, in the PMCo. The late behavioural and neurochemical activation was followed by an increase in the levels of circulating luteinizing hormone. In conclusion, these data show that only species-specific chemosignals induce a delayed behavioural activation and excitatory activation of the PMCo, which is dependent on an intact VNO. [source]

Effects of some synthetic kynurenines on brain amino acids and nitric oxide after pentylenetetrazole administration to rats

JOURNAL OF PINEAL RESEARCH, Issue 4 2004
Leila Bikjdaouene
Abstract:, We have previously proven that some synthetic kynurenines behave as antagonists of the N-methyl- d -aspartate receptor inhibiting neuronal subtype of nitric oxide synthase activity. We now investigate the anticonvulsant activity of four of these kynurenines in pentylenetetrazole (PTZ)-treated rats. The rats were treated with each kynurenine (10,160 mg/kg, s.c.) 30 min before PTZ administration (100 mg/kg, s.c.). Then, latency, duration and intensity of the first seizure and the percent animal survival were noted. PTZ-induced death was counteracted by high doses of kynurenines. Latency of the first seizure was significantly increased and its intensity reduced at the same doses, whereas the duration of the first seizure significantly decreased with doses of 20 mg/kg in most of the kynurenines tested. Three hours after PTZ administration, the surviving animals were sacrificed and the levels of brain amino acids and nitrite were measured. PTZ administration increased glutamate, glutamine, serine and taurine levels in different brain areas. High doses of kynurenines generally counteracted the effects of PTZ on excitatory amino acids, but they also reduced inhibitory aminoacids. However, the most consistent effect of kynurenines was the dose-dependent reduction of brain nitrite levels induced by PTZ. These results reveal a new family of anticonvulsant drugs that affect mainly to nitric oxide production in the brain. [source]

Effects of Acamprosate on Excitatory Amino Acids During Multiple Ethanol Withdrawal Periods

Cell Death Mechanisms Following Traumatic Brain Injury

BRAIN PATHOLOGY, Issue 2 2004
Ramesh Raghupathi PhD
Neuronal and glial cell death and traumatic axonal injury contribute to the overall pathology of traumatic brain injury (TBI) in both humans and animals. In both head-injured humans and following experimental brain injury, dying neural cells exhibit either an apoptotic or a necrotic morphology. Apoptotic and necrotic neurons have been identified within contusions in the acute post-traumatic period, and in regions remote from the site of impact in the days and weeks after trauma, while degenerating oligodendrocytes and astrocytes have been observed within injured white matter tracts. We review and compare the regional and temporal patterns of apoptotic and necrotic cell death following TBI and the possible mechanisms underlying trauma-induced cell death. While excitatory amino acids, increases in intracellular calcium and free radicals can all cause cells to undergo apoptosis, in vitro studies have determined that neural cells can undergo apoptosis via many other pathways. It is generally accepted that a shift in the balance between pro- and anti-apoptotic protein factors towards the expression of proteins that promote death may be one mechanism underlying apoptotic cell death. The effect of TBI on cellular expression of survival promoting-proteins such as Bcl-2, Bcl-xL, and extracellular signal-regulated kinases, and death-inducing proteins such as Bax, c-Jun N-terminal kinase, tumor-suppressor gene, p53, and the calpain and caspase families of proteases are reviewed. In light of pharmacologic strategies that have been devised to reduce the extent of apoptotic cell death in animal models of TBI, our review also considers whether apoptosis may serve a protective role in the injured brain. Together, these observations suggest that cell death mechanisms may be representative of a continuum between apoptotic and necrotic pathways. [source]

Investigation Of AM-36: A Novel Neuroprotective Agent

CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY, Issue 11 2001
Jk Callaway
SUMMARY 1. The neurochemical sequelae following cerebral ischaemia are complex, involving excess release of excitatory amino acids, particularly glutamate, disruption of ionic homeostasis due to Na+ and Ca2+ influx and generation of toxic free radicals, ultimately leading to cell death by both necrosis and apoptosis. 2. Drugs that block components of this biochemical cascade, such as glutamate receptor antagonists, sodium channel blockers and free radical scavengers, have been investigated as putative neuroprotective agents. The knowledge that multiple mechanisms contribute to neuronal injury in ischaemia have led to the general recognition that a single drug treatment is unlikely to be beneficial in the treatment of cerebral ischaemia. 3. AM-36 [1-(2-(4-chlorophenyl)-2-hydroxy)ethyl-4-(3,5-bis(1,1-dimethyl)-4-hydroxyphenyl)methylpiperazine] is one of a series of hybrid molecules designed to incorporate multiple neuroprotective mechanisms within the one structure. Primary screening tests demonstrated that AM-36 inhibited binding to the polyamine site of glutamate receptors, blocked neuronal sodium channels and had potent anti-oxidant activity. In neuronal cell cultures, AM-36 inhibited toxicity induced by N -methyl- D -aspartate (NMDA) and the sodium channel opener veratridine and, in addition, inhibited veratridine-induced apoptosis. 4. In a middle cerebral artery occlusion model of stroke in conscious rats, systemic administration of AM-36 markedly reduced both cortical and striatal infarct volume and significantly improved functional outcome in motor performance, neurological deficit and sensorimotor neglect tests. AM-36 was neuroprotective even when administration was delayed until 3 h systemically, or 5 h intravenously, after induction of stroke. 5. These studies indicate that AM-36 is a unique neuroprotective agent with multiple modes of action, making it an attractive candidate for the treatment of acute stroke in humans. [source]