Intravitreal and intraperitoneal administrations of sodium L-glutamate induced the retinal degenerations in adult rabbits. Electroretiongram was completely extinguished by the intravitreal injection of glutamate (50mg in 0.1ml) followed by slight recovery. The retina showed marked thinning with almost diffuse degeneration in all retinal layers. Intraperitoneal injection of a sigle large dose of glutamate(8g/Kg) produced moderate reduction in the amplitudes of a-and b-waves with degenerative changes in the retina, mainly involving the inner layers and the periphery of the fundus, parallel to the ERG changes. Administrations of small doses (2.5g/Kg and 5.0g/Kg) for 7 days induced moderate reduction in the a-and b-waves with slight histological changes, especially marked in the inner layers of the retina. Possible mechanisms of the toxic effects of glutamate were discussed.
Adult ; Glutamic Acid ; Humans ; Injections, Intraperitoneal ; Intravitreal Injections ; Rabbits* ; Retina* ; Retinal Degeneration ; Retinaldehyde ; Sodium Glutamate* ; Sodium*

Glutamate is an amino acid neurotransmitter capable of producing widespread receptor-mediated neuronal excitation. In this experiment, we examined the effect of saline, monosodium glutamate (MSG), phenylalanine and MSG-phenylalanine treatment on TH immunoreactivity in area postrema (AP) of medulla oblangata. An immunocytochemical method was used to visualize catecholaminergic neurons in the AP. Damage of TH neurons in the AP of adult Sprague-Dawley rats was induced by injection of MSG (4 mg/g bw) and was decreased by administration of MSG following phenylalanine treatment (15 mg/g bw). We conclude that phenylalanine protect from the neuroexcitotoxic effect of systemic glutamate.
Adult ; Animals ; Area Postrema* ; Glutamic Acid ; Humans ; Neurons ; Neurotransmitter Agents ; Phenylalanine* ; Rats* ; Rats, Sprague-Dawley ; Sodium Glutamate*

Diabetic hyperglycemia induces transient ischemia in the neural retina. High level of extracellular glutamate resulting from ischemia, in turn, influences on glutamate homeostasis. The present study has been conducted to clarify the alteration of the glutamate homeostasis-associated substances in the retinal Muller cells in response to a diabetic injury by streptozotocin injection. Young adult Sprague -Dawley rats were injected with streptozotocin (60 mg/kg body weight in 0.05 M sodium citrate buffer, pH 5.5) under anesthesia with 4% chloral hydrate. Animals above 300 mg/dl in blood glucose level were cared for 1, 4, 12 and 24 weeks, respectively. At each time-point, the retinas were dissected out and processed for immuno-histochemical and immunoblotting analyses by using guinea pig anti -GLAST and mouse anti-glutamine synthetase (GS) antibodies. In the normal retina, GLAST and GS were immuno-localized in the Muller cells, the outer plexiform layer (OPL), the border between the inner nuclear layer and the inner plexiform layer (IPL), a band in the middle of the IPL, and the border between the IPL and the ganglion cell layer. The expression of both proteins was decreased remarkably in the OPL by 12 weeks of diabetes and increased slightly in the end feet of the Muller cells from 4 weeks onwards. Immunoblotting results of the two proteins in the diabetic retinas were largely consistent with those of immuno-histochemistry. These results suggest that the alteration of glutamate homeostasis in the diabetic state is initiated mainly in the OPL by decreasing the uptake of glutamate via down-regulated GLAST.
Anesthesia ; Animals ; Antibodies ; Blood Glucose ; Body Weight ; Chloral Hydrate ; Citric Acid ; Ependymoglial Cells ; Foot ; Ganglion Cysts ; Glutamate-Ammonia Ligase* ; Glutamic Acid ; Glutamine* ; Guinea Pigs ; Homeostasis ; Humans ; Hydrogen-Ion Concentration ; Hyperglycemia ; Immunoblotting ; Ischemia ; Ligases ; Mice ; Rats* ; Retina* ; Sodium ; Streptozocin ; Young Adult

Orthostatic hypotension is most common in elderly people, and its prevalence increases with age. Attenuation of the vestibulo-sympathetic reflex (VSR) is commonly associated with orthostatic hypotension. In this study, we investigated the role of glutamate on the vestibulo-solitary projection of the VSR pathway to clarify the pathophysiology of orthostatic hypotension. Blood pressure and expression of both pERK and c-Fos protein were evaluated in the nucleus tractus solitarius (NTS) after microinjection of glutamate into the medial vestibular nucleus (MVN) in conscious rats with sodium nitroprusside (SNP)-induced hypotension that received baroreceptor unloading via sinoaortic denervation (SAD). SNP-induced hypotension increased the expression of both pERK and c-Fos protein in the NTS, which was abolished by pretreatment with glutamate receptor antagonists (MK801 or CNQX) in the MVN. Microinjection of glutamate receptor agonists (NMDA or AMPA) into the MVN increased the expression of both pERK and c-Fos protein in the NTS without causing changes in blood pressure. These results indicate that both NMDA and AMPA receptors play a significant role in the vestibulo-solitary projection of the VSR pathway for maintaining blood pressure, and that glutamatergic transmission in this projection might play a key role in the pathophysiology of orthostatic hypotension.
Aged ; Animals ; Blood Pressure ; Denervation ; Excitatory Amino Acid Antagonists ; Glutamic Acid* ; Humans ; Hypotension* ; Hypotension, Orthostatic ; Microinjections ; N-Methylaspartate ; Nitroprusside ; Pressoreceptors ; Prevalence ; Rats* ; Receptors, AMPA ; Receptors, Glutamate ; Reflex ; Sodium* ; Solitary Nucleus ; Vestibular Nuclei

No abstract available.
Animals ; Brain* ; Glutamic Acid* ; Glycine* ; Rats*

Sixty years elapsed since Chang (Hsiang-Tung Chang, Xiang-Tong Zhang) presented his seminal report "Cortical neurons with particular reference to the apical dendrite" at the Cold Spring Harbor Symposium. Thanks to the development of elaborated techniques through the 6 decades, our understanding of the dendrite has been pushed forward greatly: the backward and forward conductions during excitation, sodium and calcium conductances, chemical excitation by uncaging glutamate at a dimension of micrometer, and the quantitative study of chemical organization of postsynaptic density (PSD), etc. Though the progression is great, there are still tough problems in dendritic research, especially the integration through dendritic spine.
Calcium Signaling ; Dendrites ; physiology ; Glutamic Acid ; metabolism

No abstract available.
Amino Acid Transport System X-AG* ; Anesthetics* ; Glutamic Acid*

No abstract available.
Animals ; Cerebral Cortex* ; Glutamic Acid* ; Glycine* ; Kynurenic Acid* ; Perfusion* ; Rats*

BACKGROUNDMonosodium L-glutamate (MSG) is a food flavour enhancer and its potential harmfulness to the heart remains controversial. We investigated whether MSG could induce cardiac arrhythmias and apoptosis via the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor.

METHODSMyocardial infarction (MI) was created by ligating the coronary artery and ventricular arrhythmias were monitored by electrocardiogram in the rat in vivo. Neonatal rat cardiomyocytes were isolated and cultured. Cell viability was estimated by 3-(4,5)-dimethylthiahiazo(-z-yl)-3,5-di-phenytetrazoliumromide (MTT) assay. Calcium mobilization was monitored by confocal microscopy. Cardiomyocyte apoptosis was evaluated by acridine orange staining, flow cytometry, DNA laddering, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting.

RESULTSMSG (i.v.) decreased the heart rate at 0.5 g/kg and serious bradycardia at 1.5 g/kg, but could not induce ventricular tachyarrhythmias in normal rats in vivo. In rats with acute MI in vivo, however, MSG (1.5 g/kg, i.v.) induced ventricular tachyarrhythmias and these arrhythmias could be prevented by blocking the AMPA and N-methyl-d-aspartate (NMDA) receptors. Selectively activating the AMPA or NMDA receptor induced ventricular tachyarrhythmias in MI rats. At the cellular level, AMPA induced calcium mobilization, oxidative stress, mitochondrial dysfunction and apoptosis in cultured cardiomyocytes, especially when the AMPA receptor desensitization were blocked by cyclothiazide. The above toxic cellular effects of AMPA were abolished by AMPA receptor blockade or by H2O2 scavengers.

CONCLUSIONSMSG induces bradycardia in normal rats, but triggers lethal tachyarrhythmias in myocardial infarcted rats probably by hindering AMPA receptors. AMPA receptor overstimulation also induces cardiomyocyte apoptosis, which may facilitate arrhythmia.

Animals ; Apoptosis ; drug effects ; Arrhythmias, Cardiac ; chemically induced ; Calcium ; metabolism ; Cell Survival ; drug effects ; Cells, Cultured ; DNA Fragmentation ; drug effects ; Glutamic Acid ; toxicity ; Male ; Microscopy, Confocal ; Myocardial Infarction ; chemically induced ; Rats ; Rats, Wistar ; Receptors, AMPA ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sodium Glutamate ; toxicity ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid ; toxicity

Astrocytes and neurons are inseparable partners in the brain. Neurotransmitters released from neurons activate corresponding G protein-coupled receptors (GPCR) expressed in astrocytes, resulting in release of gliotransmitters such as glutamate, D-serine, and ATP. These gliotransmitters in turn influence neuronal excitability and synaptic activities. Among these gliotransmitters, ATP regulates the level of network excitability and is critically involved in sleep homeostasis and astrocytic Ca2+ oscillations. ATP is known to be released from astrocytes by Ca2+-dependent manner. However, the precise source of Ca2+, whether it is Ca2+ entry from outside of cell or from the intracellular store, is still not clear yet. Here, we performed sniffer patch to detect ATP release from astrocyte by using various stimulation. We found that ATP was not released from astrocyte when Ca2+ was released from intracellular stores by activation of Galpha(q)-coupled GPCR including PAR1, P2YR, and B2R. More importantly, mechanical stimulation (MS)-induced ATP release from astrocyte was eliminated when external Ca2+ was omitted. Our results suggest that Ca2+ entry, but not release from intracellular Ca2+ store, is critical for MS-induced ATP release from astrocyte.
Adenosine Triphosphate* ; Astrocytes* ; Brain ; Glutamic Acid ; Homeostasis ; Neurons ; Neurotransmitter Agents