Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Considerable evidence has accumulated indicating that one neurotransmitter in the excitatory cortico-striatal tract is glutamate. Lesions of the tract result in reductions in the striatum of glutamate levels as well as high affinity uptake of glutamate into synaptosomes. Furthermore, such lesions eliminate the neurotoxicity of the glutamate analog kainic acid when injected into the striatum. The fine structure of the cortico-striatal pathway was studied to provide evidence regarding the morphology of glutamate nerve endings. Seven days after injection of 3H-proline (20-25 mu Ci) into the rat frontal cortex, axonally transported label appeared in the striatum with uniform distribution in a single type of nerve ending. The labeled boutons had common round vesicles and made asymmetrical contacts, mostly with dendritic spines. This morphology is typical of excitatory synapses, and similar to that previously shown for cholinergic boutons in the striatum. In four animals similarly injected with 3H-proline, kainic acid was administered directly into the striatum to induce degeneration of postsynaptic elements eight to ten hours before sacrifice. In areas affected by these injections, grains appear in patches, possibly resulting from glial swelling. Labeled boutons were seen almost four times as often in synaptic contact with degenerating dendritic elements as with normal ones. The data provide morphological evidence as to the nature of the probable glutamatergic boutons in the striatum, and show the close relationship of such boutons with the neurotoxic effects of kainic acid. This would be anticipated in view of the dependency of kainic acid neurotoxicity on the integrity of the cortico-striatal pathway.
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PMID:Fine structural analysis of the cortico-striatal pathway. 3 35

A brief application of high K+ or excitatory amino acids (i.e. kainic acid) generated repetitive synchronized burst that persisted for the duration of the application, in the CA3 field. Once excitability has been enhanced, further stimulation of various inputs evoked burst instead the typical excitatory postsynaptic potential--inhibitory postsynaptic potential sequence evoked in control conditions. These long-lasting changes in synaptic efficacy involved the activation of glutamate receptors of N-methyl-D-aspartate (NMDA) subtype. A brief period of hyperactivity (i.e. kindling of limbic pathways or administration of kainic acid) also resulted in a more delayed synaptic remodeling, notably of hippocampal mossy fibers (i.e. the axons of granule cells that mostly contact the apical dendrites of CA3 pyramidal neurons). Thus mossy fibers sprouted and made multiple ectopic asymmetrical synapses with spines of both granule cells dendrites and basilar dendrites of CA3 pyramidal cells. Finally, sprouting of mossy fibers was associated with a significant rise in the density of kainic acid binding sites (fmol/mg tissue) in the aberrantly innervated zones: the inner third of molecular layer and the stratum oriens of CA3. Saturation studies revealed that this rise did not significantly affect the affinity (Kd values) but the Bmax. In conclusion, brief seizure episodes produced in the hippocampus remarkably long-lasting changes in synaptic efficacy; synaptic density and the mean density of excitatory amino acid receptors of non-NMDA subtype. The role that such plastic changes may play in the permanence of the epilepsy is finally discussed.
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PMID:Long-term potentiation and sprouting of mossy fibers produced by brief episodes of hyperactivity. 133 65

The presence of glutamate and GABA was examined in zinc-containing terminals of the cat visual cortex using a post-embedding immunogold method. The surface density of immunogold-labelling was also evaluated in morphologically defined ultrastructural elements, namely terminals having round synaptic vesicles and making asymmetrical synapses (RA boutons), terminals with flat vesicles and symmetrical synapses (FS) and glial cell processes. Glutamate immunoreactivity was highest in RA terminals and in zinc-containing boutons. It was lower in FS terminals and lowest in glial cell processes. GABA immunoreactivity was highest in FS terminals and low in all other ultrastructural elements analysed, including zinc-containing terminals. Therefore, zinc-containing terminals show an enrichment of glutamate and they are likely to use this amino acid as their neurotransmitter. Moreover, the fact that many RA terminals that are negative for zinc show an enrichment of immunoreactive glutamate suggests that zinc-containing fibres represent a subpopulation of the glutamate axonal network.
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PMID:Enrichment of glutamate in zinc-containing terminals of the cat visual cortex. 135 51

Four spinocervical tract cells in lumbosacral spinal cords of adult cats were physiologically characterized and intracellularly labelled with horseradish peroxidase. The neurones were examined with a light microscope and reconstructed. Selected regions were chosen for ultrastructural analysis. Thin sections were treated to reveal the presence of L-glutamate by using the postembedding immunogold method. Two antisera, which specifically recognise the presence of fixed glutamate in tissue, were used in the study. Somata, proximal, and distal dendrites of all four neurones received synaptic contacts from boutons which displayed an obvious immunogold reaction. These boutons formed between 35% and 48% of all synaptic contacts onto spinocervical tract cells. Glutamate-enriched boutons were associated with gold particle densities which were 2-3 times greater than the average densities associated with the surrounding neuropil. Their profiles had a mean diameter of 1.68 microns, contained round agranular synaptic vesicles, and formed asymmetrical synaptic junctions. However, not all boutons displaying these characteristics were enriched with glutamate. Immunogold studies of alternate thin sections, which were incubated with glutamate or GABA antiserum, demonstrated that synaptic boutons on spinocervical tract cells were either enriched with GABA or with glutamate and formed two separate populations which had distinct morphological characteristics. GABA-containing boutons contained irregularly shaped agranular vesicles and formed symmetrical synaptic junctions, whereas glutamate-enriched boutons corresponded to those described above. A further population of boutons, containing highly flattened vesicles, was not immunoreactive for GABA or glutamate. The evidence supports the idea that much of the excitatory transmission into the SCT is mediated by L-glutamate.
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PMID:Direct observations of synapses between L-glutamate-immunoreactive boutons and identified spinocervical tract neurones in the spinal cord of the cat. 136 31

Within the hypothalamus, a large number of neuroactive substances are found, many first detected in this part of the brain. Excitatory amino acids, recognized as important transmitters in other parts of the brain, have received little attention here. To study glutamate immunoreactivity at the ultrastructural level in the hypothalamus, postembedding colloidal gold or silver-intensified gold was used. Antisera raised against glutamate conjugated with glutaraldehyde to keyhole limpet hemocyanin were specific for glutamate, tested with a battery of tests including immunodot blot, ELISA assays. Western blot, and Sepharose epoxy-conjugated amino acids. Antisera did not cross-react with other amino acids and related compounds, with proteins containing glutamate, or with polyglutamate. A population of presynaptic boutons in the suprachiasmatic, arcuate, ventromedial, supraoptic, and parvocellular and magnocellular paraventricular nuclei showed strong immunoreactivity for glutamate. Highly labeled presynaptic axons generally made asymmetrical Gray type 1 synaptic contacts with dendrites or cell bodies and had up to eight times more immunogold particles per unit area than postsynaptic dendrites. Axon terminals exhibiting strong glutamate immunoreactivity had large numbers of round, clear vesicles adjacent to the synaptic specialization together with a few larger, dense-core vesicles. The largest number of gold particles over axons were located in regions containing the small clear vesicles. Axons in general had about three times more gold particles over them than did the postsynaptic dendrites. Staining of single boutons in adjacent serial ultrathin sections with glutamate or GABA antisera showed that non-GABAergic terminals had a higher level of glutamate staining than did axons immunoreactive for GABA. In control experiments, immunostaining with glutamate antiserum could be blocked by solid-phase absorption of the antiserum with glutamate conjugated with glutaraldehyde to proteins. Aspartate was also detected with immunocytochemistry in some presynaptic boutons in the medial hypothalamus. To compare the response of neurons to aspartate and glutamate, calcium-imaging dyes were used in combination with digital video microscopy. Whereas almost all neurons showed a rise in intracellular Ca2+ in response to glutamate, many but not all of the same cells also showed a Ca2+ rise of smaller magnitude in response to aspartate. These ultrastructural immunocytochemical data, taken in conjunction with biochemical and electrophysiological experiments, suggest that glutamate, and to a lesser extent aspartate, may play an important neurotransmitter role in a wide variety of hypothalamic circuits.
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PMID:Glutamate and aspartate immunoreactivity in hypothalamic presynaptic axons. 167 27

A mutant strain of Han-Wistar rat carries an autosomal recessive gene producing spastic paresis which is characterized by ataxia, tremor and hind limb rigidity. Brains of affected rats and unaffected littermate controls were transected at the mesencephalon into rostral and caudal portions (the caudal portion contained the cerebellum and brainstem). Poly(A)+ mRNA was isolated from pooled rostral or caudal portions and injected into Xenopus oocytes. The oocytes were voltage-clamped and exposed to 1 mM L-glutamate, 500 microM kainate, 500 microM quisqualate, 200 microM N-methyl-D-aspartate (NMDA) or 1 mM gamma-aminobutyric acid (GABA). Oocytes injected with mRNA isolated from the caudal portions of the affected rat brains exhibited statistically significant increases in glutamate and kainate peak current responses compared to oocytes injected with mRNA from other brain samples. No differences were noted in the responses of the groups when exposed to quisqualate, NMDA or GABA. Cerebellar and brain stem mRNA were also isolated separately in different groups of mutants and unaffected littermates. Only oocytes injected with cerebellar mRNA from mutants displayed statistically significant increases in responses to glutamate and kainate. In parallel morphological studies changes in the cerebellum of mutants were also observed. These consisted of a loss of Purkinje cells and an asymmetrical disarrangement of the granule cell layer of cerebellar cortex. Taken together, the physiological and morphological results suggest that alterations in glutamate/kainate receptors in the cerebellum are phenotypic manifestations of the Han-Wistar mutation. The results are consistent with the hypothesis that this mutant rat might serve as a model of glutamate/kainate excitotoxicity in the brain.
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PMID:Altered excitatory amino acid function and morphology of the cerebellum of the spastic Han-Wistar rat. 168 5

The distribution and morphology of neurons labelled with antisera to glutamate or aspartate were examined, at the light and electron microscope levels, in the rat visual cortex. Using widely accepted light microscopic features as well as well-established nuclear, cytoplasmic, and synaptic criteria, we noted that glutamate-immunoreactive neurons were pyramidal cells distributed in layers II-VI, with an increased concentration in layers II and III. Aspartate immunoreactivity was localized chiefly to pyramidal neurons in layers II-VI. However, approximately 10% of immunolabeled cells were nonpyramidal neurons scattered throughout the cortex. Cell-body measurements revealed that, for both groups of neurons, layer V contained the largest labelled neurons, whereas layers IV and VI contained the smallest. Furthermore, in every layer, aspartate-stained neurons were larger than glutamate-positive cells. Finally, glutamate- and aspartate-labelled axon terminals formed asymmetrical synapses, which are presumably excitatory in nature, primarily with dendritic spines. These findings, together with recent detailed studies of the projections of glutamate- and aspartate-labelled cortical neurons, may provide essential background information for studies aimed to elucidate the function(s) of excitatory amino acids in the cortex and their role in pathological conditions.
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PMID:Excitatory transmitter amino acid-containing neurons in the rat visual cortex: a light and electron microscopic immunocytochemical study. 257 98

Myelinated axons were isolated from the sciatic nerve of Xenopus laevis and were subjected to localized (less than 30 microns wide) lesions. In axons which were bathed in a 0.12 M potassium glutamate solution there was very little local reaction to the lesion and optically-detectable particles undergoing axoplasmic transport accumulated immediately adjacent to, and mostly distal to, the lesion. Preparations fixed for electron microscopy at times up to 3 h following the lesion showed that the axoplasmic changes about the lesion were asymmetrical. Large organelles predominated on the distal side of the lesion; these were mostly dense lamellar bodies (DLB) with mean dimensions, as determined from thin sections, of 0.48 by 0.19 microns. Multivesicular bodies, mitochondria, and a variety of smaller membrane bounded bodies also appeared in the particle accumulation distal to the lesion. Analysis of these results led to the conclusion that DLB were transported up to the lesion and represent the majority of the optically detectable particles which are transported in the retrograde direction. Small vesicles and tubules were the commonest structures which accumulated proximal to the lesion. The time course of this accumulation was consistent with the hypothesis that these structures are particulate bodies which move in the orthograde direction at about 1.5 microns/s. Incidental findings which are also of significance to the study of axonal transport were: large particulate material may reverse its direction of movement at an axonal obstruction, and organelles which accumulate on either side of a lesion do so in rows which are associated with microtubules.
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PMID:The short term accumulation of axonally transported organelles in the region of localized lesions of single myelinated axons. 616 22

In order to clarify the origin and to examine the neurochemistry and synaptology of the projection from the mesopontine tegmentum (MTg) to the subthalamic nucleus (STN), rats received discrete deposits of anterograde tracers in different regions of the MTg. Anterogradely labeled fibers were examined in the light and electron microscopes. The distribution of GABA or glutamate immunoreactivity was examined by post-embedding immunocytochemistry. The anterograde tracing demonstrated that the projection to the STN arises from at least three divisions of the MTg: the area defined by the cholinergic neurons of the pedunculopontine region (PPN-Ch 5), the more medial and largely noncholinergic midbrain extrapyramidal area (MEA) and to a lesser extent the laterodorsal tegmental nucleus (LDTg). Post-embedding immunocytochemistry revealed that there are GABA-immunopositive and immunonegative components to this projection and at least a proportion of the GABA-immunonegative component is enriched in glutamate immunoreactivity. The similarity of the morphology, trajectory and synaptology of the anterogradely labeled fibers and the choline acetyltransferase (ChAT)-immunopositive fibers supports the proposal that at least part of the projection is cholinergic. The terminals anterogradely labeled from the MTg and the ChAT-immunoreactive terminals form asymmetrical synapses with the dendrites and spines of subthalamic neurons. Both anterogradely labeled and ChAT-positive terminals make convergent synaptic contacts with GABA-immunoreactive terminals that form symmetrical synaptic contacts and are probably derived from the globus pallidus. Taken together these findings imply that the MTg sends cholinergic, GABAergic and glutamatergic projections to the STN where at least one of the functional roles is to modulate the indirect pathway of information flow through the basal ganglia that is carried via the pallidosubthalamic projection.
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PMID:Cholinergic, GABAergic, and glutamate-enriched inputs from the mesopontine tegmentum to the subthalamic nucleus in the rat. 747 65

The mitral cell of the olfactory bulb is the primary relay neuron that transmits information from the olfactory receptors to the rest of the brain. This excitatory neuron releases glutamate from presynaptic dendrites and axon terminals. All rat mitral cells studied showed strong, selective, and widespread metabotropic glutamate receptor mGluR1 alpha immunoreactivity on the presynaptic membrane of dendrites, often at the synaptic vesicle release site, when examined with light and electron microscopy. The finding of glutamate receptors on mitral cell secondary dendrites supports the conclusion that not all dendritic membrane with glutamate receptors necessarily have gray type I asymmetrical synaptic specializations. In contrast, the metabotropic glutamate receptor mGluR5 was not found in mitral cells but was expressed by granule cells and astrocytes around mitral dendrites. Both mGluR1 alpha and mGluR5 were expressed early in development, with strong immunostaining present by postnatal day 1. MGluR1 alpha staining at birth mirrored the adult staining pattern. MGluR5 staining at birth showed different patterns of immunostaining than that found in the adult, particularly in the external plexiform layer. In vitro olfactory bulb neurons and their dendrites from embryonic day (E) 18 olfactory bulbs responded to t-ACPD and quisqualate, selective and nonselective metabotropic glutamate receptor agonists, and to several ionotropic glutamate agonists with increases in intracellular Ca2+ as studied with fura-2 digital imaging. These data indicate that the receptors were functionally active at an early stage of development. Application of the glutamate receptor blockers d-2-amino-5-phosphonovalerate (AP5) and 6-cyano-7-nitroquinoxaline (CNQX) to E17 olfactory bulb neurons after only 4 days in vitro resulted in a dramatic decrease in Ca2+ levels in 70% of 128 cells tested, suggesting that embryonic neurons after a short time in vitro can actively secrete glutamate. The presence of glutamate receptors on the long mitral cell dendrite suggests that it would be able to respond to release of its own excitatory transmitter, probably at an early stage of development. In the probable absence of other excitatory input to the secondary mitral dendrites, it would be the only excitatory "input." This autoexcitatory response would be modulated by release of GABA from olfactory interneurons occurring milliseconds after glutamate release induced by olfactory nerve activation. This novel type of neuronal microcircuitry would potentially amplify signal transmission and current spread along the long mitral dendrites and could play an important role in lateral inhibition of olfactory neurons.
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PMID:Presynaptic metabotropic glutamate receptors in adult and developing neurons: autoexcitation in the olfactory bulb. 749 28


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