Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:4.1.1.15 (glutamate decarboxylase)
2,169 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gangliogliomas, dysembryoplastic neuroepithelial tumors (DNT) and glioneuronal malformations are frequently encountered in patients with pharmacoresistant focal epilepsies. In order to characterize the neurochemical profile of these neoplastic and malformative glioneuronal lesions, we have examined the presence of the alpha 1 subunit of the GABAA receptor, the N-methyl-D-aspartate receptor subunit 1 (NR1), glutamate decarboxylase, tyrosine hydroxylase, somatostatin, parvalbumin, and calretinin in 60 gangliogliomas, 11 DNT, 10 tuberous sclerosis-like lesions and 17 non-tuberous sclerosis-like glioneuronal malformations. All DNT and tuberous sclerosis-like lesions, 59 gangliogliomas (98%), and 13 non-tuberous sclerosis-like hamartias (76%) were positive for at least one of the markers. Despite a great variation between and within the different entities, the neurochemical profile was generally reminiscent of normal neocortex: glutamate decarboxylase, GABAA receptor and NR1 which are common in neocortical neurons were present in the great majority of the lesions and often showed high labeling indices. There were three tuberous sclerosis-like lesions (30%) that contained both NR1 and glutamate decarboxylase immunoreactive giant cells in addition to well-differentiated ganglion cells. This supports the idea that at least some of these giant cells are of neuronal origin. The oligodendroglia-like cells of DNT and glioneuronal hamartias did not show immunoreactivity for any of the markers. The very high incidence of ganglioglial lesions in patients with chronic focal epilepsies and the presence of neurotransmitter-producing enzymes, neurotransmitter receptors, neuropeptides, and calcium-binding proteins in many of these lesions suggests that they may play an active role in the pathogenesis of epileptic seizures.
...
PMID:Neurochemical profile of glioneuronal lesions from patients with pharmacoresistant focal epilepsies. 766 58

Inhibitory neurons in the entorhinal cortex control information flow between the cortical areas and the hippocampus. We characterized the inhibitory circuits in the rat entorhinal cortex by analyzing the distribution of calretinin-immunoreactivity and its colocalization with glutamate decarboxylase (GAD) and gamma-aminobutyric acid (GABA). The location of calretinin-immunoreactive (IR) neurons and terminals varies between the different layers and subfields of the entorhinal cortex. The immunopositive neurons can be divided into two major morphological classes: bipolar and multipolar, which have two or more long, aspiny or sparsely spiny dendrites that extend through several layers. In addition, there are unclassified immunopositive neurons that have large lightly stained somata. They are located primarily in layer V. Colocalization analyses with GAD and GABA revealed that approximately 40% (657 out of 1,777) of all calretinin-IR cells within the entorhinal cortex contain GAD or GABA. In layers I-III, over 90% of the calretinin-IR neurons contain GAD or GABA. In layers V-VI, however, most of the calretinin-IR neurons do not colocalize with either GAD or GABA. The distribution patterns of calretinin-immunoreactivity in the entorhinal cortex is consistent with the partitioning of the rat entorhinal cortex into six subfields. Furthermore, calretinin is expressed in a morphologically heterogeneous population of cells in the rat entorhinal cortex which includes both GABAergic and non-GABAergic neurons.
...
PMID:Distribution of calretinin-immunoreactivity in the rat entorhinal cortex: coexistence with GABA. 903 97

Lesioning of the mammalian striatum with the excitotoxin quinolinic acid results in a pattern of neuropathology that resembles that of post mortem Huntington's disease brain. Certain neurotrophic factors can rescue degenerating cells in a variety of lesion types, including those produced by neurotoxins. Several neurotrophic factors promote the survival of striatal neurons and/or are localized within the striatum. Of these factors, neurotrophin-4/5 and transforming growth factor-alpha were chosen for administration to rats lesioned with quinolinic acid. Adult rats received a single unilateral intrastriatal injection of quinolinic acid (120 nmol) and either trophic factors or the control protein cytochrome c for seven days thereafter. The pattern of phenotypic degeneration was assessed by immunocytochemical labeling of various striatal neuronal populations at five rostrocaudal levels. Quinolinic acid produced a preferential loss in the number of cells immunoreactive for glutamate decarboxylase, with a relative sparing of the number of choline acetyltransferase-immunoreactive cells and, to a lesser degree, calretinin-immunoreactive cells. None of these phenotypic populations was protected by either neurotrophin-4/5 or transforming growth factor-alpha. In contrast, when glutamate decarboxylase cells were alternatively identified by calbindin immunolabeling, both factors were found to have partially reversed the loss in the number of calbindin-positive cells induced by excitolesioning. In addition, the loss in the number of parvalbumin-immunopositive cells due to quinolinic acid was partially reversed by neurotrophin-4/5, while the loss in the number of NADPH-diaphorase-stained cells was partially reversed by transforming growth factor-alpha. These findings reveal a new population of striatal cells, calretinin neurons, that are relatively resistant to quinolinic acid toxicity and that neurotrophin-4/5 and transforming growth factor-alpha partially protect against the phenotypic degeneration of striatal cell populations in an in vivo animal model of Huntington's disease.
...
PMID:Protective effects of neurotrophin-4/5 and transforming growth factor-alpha on striatal neuronal phenotypic degeneration after excitotoxic lesioning with quinolinic acid. 913 90

Corticotropin releasing hormone (CRH) has been localized to interneurons of the mammalian cerebral cortex, but these neurons have not been fully characterized. The present study determined the extent of co-localization of CRH with glutamate decarboxylase (GAD) and calcium-binding proteins in the infant rat neocortex using immunocytochemistry. CRH-immunoreactive (ir) neurons were classified into two major groups. The first group was larger and consisted of densely CRH-immunostained small bipolar cells, predominantly localized to layers II and III. The second group of CRH-ir cells was lightly labeled and included multipolar neurons mainly found in deep cortical layers. Co-localization studies indicated that the vast majority of CRH-ir neurons, including both bipolar and multipolar types, was co-immunolabeled for GAD-65 and GAD-67. Most multipolar, but only some bipolar, CRH-ir neurons also contained parvalbumin, while CRH-ir neurons rarely contained calbindin or calretinin. These results indicate that virtually all CRH-ir neurons in the rat cerebral cortex are GABAergic. Furthermore, since parvalbumin is expressed by cortical basket and chandelier cells, the co-localization of CRH and parvalbumin suggests that some cortical CRH-ir neurons may belong to these two cell types.
...
PMID:Co-localization of corticotropin-releasing hormone with glutamate decarboxylase and calcium-binding proteins in infant rat neocortical interneurons. 986 Feb 72

Recent electrophysiological observations suggest that, in addition to the medial septal area pacemaker system, several alternative or additional mechanisms are involved in the generation/regulation of hippocampal theta activity. Discharging neurons phase-locked to hippocampal theta waves have been observed in the dorsal raphe, nucleus reticularis pontis oralis and especially in the supramammillary region of rats. Since these areas are reciprocally interconnected with the hippocampal formation, including the entorhinal cortex, it would aid our understanding of limbic function to elucidate the location and neurochemical content of the entorhino-septal and septo-supramammillary projection neurons, as well as that of their postsynaptic targets. Light and electron microscopic immunostaining for calretinin, in combination with antero- and retrograde tracer techniques, postembedding immunostaining for GABA and the transmitter specific [3H]D-aspartate retrograde radiolabeling, as well as a co-localization experiment for calretinin and glutamate decarboxylase in rat supramammillary and septal neurons, demonstrated that: (i) a large population of entorhinal cells that forms asymmetric synaptic contacts on calretinin-containing neurons located at the border between the medial and lateral septal areas contains calretinin and are aspartate/glutamatergic; (ii) the overwhelming majority of calretinin-immunoreactive cells located at the border between the lateral and medial septal area are GABAergic; (iii) these neurons can be retrogradely labeled from the supramammillary area; (iv) anterogradely labeled axons originating in the border between the medial and lateral septum are GABAergic and (v) terminate on supramammillary area non-GABAergic, calretinin-containing neurons, which are known to project to the septal complex and hippocampus. These observations indicate that a large population of cells participating in the hippocampal feedback regulation of theta regulation/generation contain the same calcium-binding protein. Furthermore, entorhinal excitatory transmitter-containing neurons can depress the activity of supramammillary theta generating/regulating cells via septal inhibitory neurons.
...
PMID:The entorhino-septo-supramammillary nucleus connection in the rat: morphological basis of a feedback mechanism regulating hippocampal theta rhythm. 1036 11

Huntington disease is characterized by the selective loss of striatal neurons, particularly of medium-sized spiny glutamate decarboxylase67 staining/GABAergic projection neurons which co-contain the calcium binding protein calbindin. Lesioning of the adult rat striatum by intrastriatal injection of the N-methyl-D-aspartate receptor agonist quinolinic acid (100 nmol) results in a pattern of striatal neuropathology seven days later that resembles that seen in the Huntington brain. Using this animal model of human Huntington's disease we investigated the effect of daily intrastriatal infusion of the nerve cell survival molecule ActivinA (single bolus dose of 0.73 microg daily for seven days) on the quinolinic acid-induced degeneration of various striatal neuronal phenotypes. By seven days, unilateral intrastriatal infusion of quinolinic acid produced a partial but significant loss (P < 0.01) in the number of striatal neurons immunoreactive for glutamate decarboxylase (to 51.0+/-5.8% of unlesioned levels), calbindin (to 58.7+/-5.1%), choline acetyltransferase (to 68.6+/-6.1%), NADPH-diaphorase (to 47.4+/-5.4%), parvalbumin (to 58.8+/-4.1%) and calretinin (to 60.6+/-8.6%) in adult rats that were administered intrastriatal phosphate-buffered saline for seven days following quinolinic acid. In contrast, in rats that received intrastriatal recombinant human ActivinA once daily for seven days following quinolinic acid, phenotypic degeneration was significantly attenuated in several populations of striatal neurons. Treatment with ActivinA had the most potent protective effect on the striatal cholinergic interneuron population almost completely preventing the lesion induced decline in choline acetyltransferase expression (to 95.1+/-5.8% of unlesioned levels, P < 0.01). ActivinA also conferred a significant protective effect on parvalbumin (to 87.5+/-7.7%, P < 0.01) and NADPH-diaphorase (to 77.5+/-7.5%, P < 0.01) interneuron populations but failed to prevent the phenotypic degeneration of calretinin neurons (to 56.6+/-5.5%). Glutamate decarboxylase67 and calbindin-staining nerve cells represent largely overlapping populations and both identify striatal GABAergic projection neurons. We found that ActivinA significantly attenuated the loss in the numbers of neurons staining for calbindin (to 79.7+/-6.6%, P < 0.05) but not glutamate decarboxylase67 (to 61.1+/-5.9%) at seven days following quinolinic acid lesioning. Taken together these results suggest that exogenous administration of ActivinA can rescue both striatal interneurons (labelled with choline acetyltransferase, parvalbumin, NADPH-diaphorase) and striatal projection neurons (labelled by calbindin) from excitotoxic lesioning with quinolinic acid. Longer-term studies will be required to determine whether these surviving calbindin-expressing projection neurons recover their ability to express the glutamate decarboxylase67/GABAergic phenotype. These results therefore suggest that treatment with ActivinA may help to prevent the degeneration of vulnerable striatal neuronal populations in Huntington's disease.
...
PMID:Administration of recombinant human Activin-A has powerful neurotrophic effects on select striatal phenotypes in the quinolinic acid lesion model of Huntington's disease. 1039 42

Within the rodent visual system, calcitonin gene-related peptide (CGRP) is selectively expressed in neurons in the accessory optic nuclei (AON), including the dorsal terminal nucleus (DTN), lateral terminal nucleus (LTN) and medial terminal nucleus (MTN). To determine whether CGRP-immunoreactive neurons are involved in visual circuitry, electron microscopic preparations were analyzed from normal rats and rats with optic nerve transections. A co-localization analysis was also made because CGRP-labeled neurons had features of GABAergic neurons. Thus, sections were prepared for light microscopy to determine whether CGRP-containing neurons also had glutamate decarboxylase (GAD) and other markers for GABAergic neurons, such as calcium binding proteins: calbindin (CB), calretinin (CR) and parvalbumin (PV). Electron microscopy of the DTN and LTN showed CGRP-labeled somata and dendrites that were postsynaptic to axon terminals forming asymmetric synapses. Many of these axon terminals degenerated following optic nerve transection indicating that retinal ganglion cells form synapses with CGRP-labeled neurons in the AON. In the DTN, LTN and MTN, CGRP-labeled axon terminals formed symmetric synapses with unlabeled somata as well as dendritic shafts and spines. Consistent with this type of synapse being GABAergic were the co-localization data showing that about 90% of the CGRP-labeled neurons co-localized GAD in the AON. Many CGRP-labeled neurons showed immunostaining for CR (40%) whereas only a few had labeling for CB (5%). No CGRP-labeled neurons had PV. These data show that CGRP-containing neurons receive direct retinal input and represent a subpopulation of GABAergic neurons which differentially co-express calcium-binding proteins.
...
PMID:Synaptic and neurochemical features of calcitonin gene-related peptide containing neurons in the rat accessory optic nuclei. 1044 24

Huntington's disease is an incurable genetic neurological disorder characterized by the relatively selective degeneration of the striatum. Lesioning of the striatum in rodents using the excitatory amino acid agonist, quinolinic acid (QA), effectively mimics the human neuropathology seen in Huntington's disease. Using this animal model of Huntington's disease, we investigated the ability of the insulin-like growth factor-I (IGF-I) amino-terminal tripeptide glycine-proline-glutamate (GPE) to protect striatal neurons from degeneration. Adult rats received a single unilateral intrastriatal injection of QA (100 nmol) and then daily injection of either vehicle or GPE (0.3 microgram/microliter/day) into the striatum for 7 days. QA at this dose resulted in a partial lesioning of the striatum after 7 days to approximately 50% of cells of unlesioned levels in vehicle-treated animals. The major striatal neuronal phenotype, GABAergic projection neurons, were identified by immunocytochemical labeling of either glutamate decarboxylase 67 (GAD(67)) or the calcium binding protein calbindin in alternate sections. Treatment with GPE for 7 days reversed the loss in projection neurons when assessed by counts of calbindin-stained cells; however, these rescued cells did not regain immunologically detectable levels of GAD(67). GPE also significantly reversed the phenotypic degeneration of cholinergic interneurons identified by immunolabeling for choline acetyltransferase (ChAT) and NADPH diaphorase interneurons identified histochemically. GPE treatment failed to rescue the calcium binding protein interneuron populations of parvalbumin and calretinin neurons. These findings reveal that exogenous administration of GPE selectively prevents excitotoxin induced phenotypic degeneration of striatal projection neurons and cholinergic and NADPH diaphorase interneurons in an animal model of Huntington's disease.
...
PMID:The IGF-I amino-terminal tripeptide glycine-proline-glutamate (GPE) is neuroprotective to striatum in the quinolinic acid lesion animal model of Huntington's disease. 1048 77

Recent studies have demonstrated that hippocampal interneurons possess distinct cytoskeletal and cell-signaling proteins in comparison to hippocampal principal cells; however, little is known about the differences in the actin cytoskeleton between these two populations. This study examined the immunoreactivity of alpha-actinin-2, an actin binding/N-methyl-D-aspartate-receptor linking protein, in the rat hippocampal formation using double-labelling immunofluorescence. Alpha-actinin-2 immunoreactivity is seen throughout the hippocampus with heavy labeling observed in the dendrites of granule cells, in CA2 pyramidal cells and in presumed interneuronal somata throughout the dentate gyrus and CA1. All the cells with heavy somatic alpha-actinin-2 immunoreactivity in the dentate gyrus and CA1 were GABAergic interneurons labeled by glutamate decarboxylase (99%). Examination of the neurochemical marker content of the alpha-actinin-2 immunoreactive interneurons revealed that the majority of this population was neuropeptide-Y-positive and a minority was positive for calretinin. Fluid percussion head trauma did not result in significant alterations of alpha-actinin-2 immunoreactivity in hippocampal interneurons. The developmental profile of alpha-actinin-2 immunoreactivity showed the presence of alpha-actinin-2 in the hippocampus at P1, labeling of interneurons by P7 and the adult staining pattern seen by P21. This study demonstrates that principal cells and interneurons are differentially immunoreactive for alpha-actinin-2, and that alpha-actinin-2 staining is restricted to a subpopulation of interneurons. Each of the three classes of cytoskeletal elements have been shown to be differentially expressed in hippocampal interneurons and principal cells, suggesting that the cytoskeleton is a defining feature of neuronal populations. Additionally, the limited expression of alpha-actinin-2 could have important functional implications in N-methyl-D-aspartate receptor localization and modulation.
...
PMID:Differential immunoreactivity for alpha-actinin-2, an N-methyl-D-aspartate-receptor/actin binding protein, in hippocampal interneurons. 1124 49

Deficits in a variety of different neurochemical species are consistent with a loss of cortical gamma-aminobutyric acid (GABA)ergic interneurons in schizophrenia. As well as neurochemical markers that indicate all neurons using GABA as a transmitter, and which include GABA uptake sites and glutamate decarboxylase, deficits of certain neuropeptides and calcium binding proteins coexisting with GABA have been reported. These abnormalities are indicative of losses specific to certain subtypes of GABAergic neurons. The calcium binding proteins in particular demonstrate selective deficits; we find losses of parvalbumin- and calbindin-, but not calretinin-immunoreactive cells in the prefrontal cortex in schizophrenia. These selective reductions in the density of parvalbumin- and calbindin-containing neurons could reflect functional loss of expression in intact cells or alternatively a deficit in the density of certain GABAergic neuronal subtypes. The latter interpretation is consistent with a neurodevelopmental pathogenesis involving neuronal damage at a time prior to the expression of these protective calcium-binding proteins. In this review we discuss the evidence for altered GABAergic transmission in schizophrenia.
...
PMID:Neurochemical correlates of cortical GABAergic deficits in schizophrenia: selective losses of calcium binding protein immunoreactivity. 1157 54


1 2 3 Next >>

---