Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.15 (glutamate decarboxylase)
 2,169 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The basket cells are an important cell type in the dentate gyrus because their axon terminals form a prominent plexus with the somata of the principal cells, the granule cells. The basket cells consist of five morphological types that have different dendritic arborizations and somal positions. All five types of basket cell display immunoreactivity for glutamate decarboxylase, the synthesizing enzyme for the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Electron microscopy has shown that basket cells have similar ultrastructural features including smooth dendrites, infolded nuclei, intranuclear rods, prominent Nissl bodies, and a thick rim of perikaryal cytoplasm. The axon terminals of basket cells form symmetric synapses with the somata and proximal dendrites of granule cells. Since the somata, basal dendrites and proximal apical dendrites of basket cells are postsynaptic to granule cell axon collaterals, the basket cells are linked to granule cells in a powerful feedback inhibitory circuit. The basket cells are also involved in feedforward inhibition as a result of being postsynaptic to perforant path and commissural axons. The calcium-binding protein, parvalbumin, is found in each type of basket cell but less than 40% of the basket endings display parvalbumin-immunoreactivity. In contrast, virtually all cortical basket cells contain parvalbumin, and this difference for basket cells between neocortex and hippocampus may contribute to the lower seizure threshold for the hippocampal formation as compared to the neocortex. Studies show that basket cells play a role in at least two experimental models of epilepsy.
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PMID:Local circuitry of GABAergic basket cells in the dentate gyrus. 133 68

Synaptic transmission can be blocked very efficiently by inhibitory synapses on axon initial segments. Inhibitory chandelier cells forming synapses on the axon initial segment of pyramidal neurons have been found in the neocortex and hippocampus proper. Here we describe an axo-axonic local circuit neuron in the rat fascia dentata that establishes synaptic contacts with axon initial segments of numerous dentate granule cells. Examination of a large number of Golgi-impregnated nongranule cells in the fascia dentata of rats revealed a group of neurons with characteristics of chandelier cells. Thus these cells exhibited an extensive axonal plexus within the granular layer that characteristically formed vertical aggregations of axonal varicosities. The cell bodies of these neurons were located in the inner molecular layer or in the outer part of the granular layer. Their dendrites invaded the molecular layer, suggesting an afferent innervation similar to that of the granule cells. Well impregnated putative axo-axonic cells were gold-toned for an electron microscopic analysis. The cell bodies and dendrites of these neurons exhibited characteristic ultrastructural features of nongranule cells, i.e., large amounts of perinuclear cytoplasm, infoldings of the nuclear membrane, and a large number of synaptic contacts on the perikaryon and on the smooth dendritic shafts. The axon originating from the cell body or from a proximal dendrite gave rise to numerous vesicle-filled varicosities that almost exclusively formed symmetric synaptic contacts with axon initial segments. A semiquantitative study of five axonal complexes demonstrated that 92.3% of identified postsynaptic elements were initial segments of granule cell axons. Immunostaining with antibodies against glutamate decarboxylase (GAD) and parvalbumin (PARV) revealed a subpopulation of neurons that very much resembled the Golgi-impregnated axo-axonic cells with regard to cell body location, dendritic arborization, and fine structural characteristics of perikarya and dendrites. GAD and PARV were found to be coexistent in these cells. Moreover, we found GAD- and PARV-immunoreactive terminals in symmetric synaptic contact with axon initial segments of granule cells. The present study has shown a hitherto unknown axo-axonic cell in the rat fascia dentata. On the basis of our immunocytochemical findings, we hypothesize that this cell exerts a strong inhibitory effect on dentate granule cells. This way, signal transmission from the fascia dentata to the hippocampus proper within the "trisynaptic pathway" can efficiently be controlled by a group of highly specialized neurons.
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PMID:Axo-axonic chandelier cells in the rat fascia dentata: Golgi-electron microscopy and immunocytochemical studies. 169 Feb 25

A combination of retrograde transport of horseradish peroxidase or wheat germ agglutinin-colloidal gold with either single or double-label immunohistochemistry is used to describe the comparative topographic distribution of parvalbumin- and choline acetyltransferase-immunoreactive septal neurons that project to the hippocampal formation of the rat. The morphometric parameters of the retrogradely labelled, parvalbumin-containing neurons were very similar, if not identical, to those neurons of the midline and medial part of the medial septum and the diagonal band regions that had previously been shown to be immunoreactive for gamma-aminobutyric acid or for glutamate decarboxylase following colchicine treatment. The total number of parvalbumin-immunoreactive and choline acetyltransferase-positive retrogradely labelled cells was counted at 9 representative levels through the rostrocaudal extension (from 2.4 mm anterior to the level of bregma) of the medial septal-diagonal band complex. In the whole medial septum-vertical limb of the diagonal band region, about 33% of the total retrogradely labelled neurons showed immunoreactivity to parvalbumin, whereas the parvalbumin-negative cells were mainly choline acetyltransferase-immunopositive. In comparison with the average figure, the proportion of the retrogradely labelled parvalbumin-containing neurons was higher in the middle part (around 1.5 mm anterior to the bregma) than in either the rostral or caudal ends. The reverse was true for the distribution of the cholinergic septohippocampal neurons. At the maximum levels the parvalbumin-immunoreactive neurons accounted for more than half of the total retrogradely labelled cells in 4 out of 6 rats. Moreover, within the complexity of the septal neurons, a marked regularity of topographic organisation was observed in the distribution of retrogradely labelled parvalbumin-containing GABAergic and choline acetyltransferase-positive cholinergic neurons as if they were subdivided cytoarchitectonically.
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PMID:Distribution of septohippocampal neurons containing parvalbumin or choline acetyltransferase in the rat brain. 221 9

The normal morphology and distribution of parvalbumin-containing neurons (shown in a previous study to be GABAergic nerve cells) of the medial septal-diagonal band region of the adult rat brain have been studied, and the findings compared with observations on choline acetyltransferase-immunoreactive neurons. The two antigens were visualized either in the same sections using a double-label immunohistochemical procedure for the simultaneous localization of parvalbumin and choline acetyltransferase, or in immediately adjacent sections. In double-stained sections of the whole medial septal-diagonal band complex, about 34% of the total neurons showed immunoreactivity to parvalbumin; the proportion of parvalbumin-labelled neurons was slightly higher in the medial septal-vertical limb of the diagonal band region, and much lower in the horizontal limb of the diagonal band region. The distribution of parvalbumin- and choline acetyltransferase-containing neurons also varied markedly between different mediolateral subdivisions of the medial septum: about 30, 65 and 2% of the parvalbumin-immunoreactive neurons were present in the midline, medial and lateral part of the medial septum, respectively. At different rostrocaudal levels, the proportion of parvalbumin- and choline acetyltransferase-positive neurons varied in a consistent manner, and the largest number of parvalbumin-containing neurons was found at the level 1.9 mm anterior to the bregma. In the absence of reliable immunocytochemical methods for the localization of glutamate decarboxylase and GABA, parvalbumin may serve as a good marker for studying the distribution of GABAergic neurons in the medial septum-diagonal band region. Moreover, the precise maps reported in the present study of the topographic localization of parvalbumin-containing GABAergic and choline acetyltransferase-immunoreactive cholinergic nerve cells in the medial septal-diagonal band complex will serve as a useful guide in future morphological and electrophysiological studies on the septum and its efferents.
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PMID:Topographical localization of neurons containing parvalbumin and choline acetyltransferase in the medial septum-diagonal band region of the rat. 221 23

The calcium-binding protein parvalbumin (PARV) is supposed to have a protective function under conditions of experimental seizure and hypoxia in a subgroup of GABAergic inhibitory neurons in the adult rat hippocampus. Here we studied the appearance of PARV immunoreactivity in rat hippocampal non-pyramidal cells during postnatal development in comparison to glutamate decarboxylase (GAD) immunoreactivity. PARV-immunoreactive neurons were not observed before postnatal day 7 whereas GAD-positive neurons and terminal-like puncta were present at postnatal day 2 (P2) and were frequent around P5. From other studies it is known that all GABAergic neurons are formed prenatally. Our data thus indicate that in the early postnatal period GABAergic non-pyramidal cells are poorly protected by calcium-binding proteins against a pathological calcium influx.
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PMID:Late appearance of parvalbumin-immunoreactivity in the development of GABAergic neurons in the rat hippocampus. 227 61

Perfusion-fixed tissue blocks were incubated in high molar sucrose solutions, shock frozen in melting isopentane, and sectioned on a conventional cryostat. Semithin sections (2-4 microns) alternatingly stained for parvalbumin and glutamate decarboxylase enabled us to demonstrate the coexistence of both antigens in the same cell. Thick sections (40 microns) of central and peripheral nervous system tissue were immunostained and processed for correlated light and electron microscopic studies. At the electron microscopic level, the preservation of ultrastructural features such as membranes and synaptic contacts was comparable to that normally seen in vibratome sectioned material. Hence, this technique can successfully be used for preembedding coexistence studies and electron microscopic preembedding immunocytochemistry when vibratome sectioning is problematic.
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PMID:Cryostat sections for coexistence studies and preembedding electron microscopic immunocytochemistry of central and peripheral nervous system tissue. 280 93

Retinal horizontal cells receive synaptic input from photoreceptors and provide a pathway for lateral interactions in the vertebrate retina. In nonmammalian retinas, the H1 horizontal cells appear to use gamma-amino butyric acid (GABA) as their neurotransmitter. The transmitter used by mammalian horizontal cells, however, remains to be identified. In the present study, we have employed in situ hybridization to examine whether cat retinal horizontal cells contain L-glutamic acid decarboxylase (GAD) mRNA and hence might use GABA as their transmitter. In the cat retina, labeled cell bodies were found in the inner nuclear layer and the ganglion cell layer. No labeled cells were found in the photoreceptor layer. In the inner nuclear layer, labeled somata were present at two locations. The majority of them (approximately 72%) were located in the vitread side of the inner nuclear layer bordering the inner nuclear layer/inner plexiform layer boundary. A second class of labeled cells in the inner nuclear layer (approximately 20%) had larger somata and were present at the inner nuclear layer/outer plexiform layer boundary. Double labeling experiments with antisera to parvalbumin, a horizontal cell marker, showed that these perikarya belonged to horizontal cells. RNA blot analysis showed that cat retina contains a single species of GAD mRNA that is about 4 kb in size. These data show that in addition to GABAergic amacrine, displaced amacrine, and interplexiform cells described previously, horizontal cells contain GAD mRNA and may use GABA as their neurotransmitter. Hence, GABA may be a transmitter that is involved in lateral inhibition in both nonmammalian and mammalian retinas.
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PMID:Localization of L-glutamic acid decarboxylase mRNA in cat retinal horizontal cells by in situ hybridization. 280 51

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.
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PMID:Neurochemical profile of glioneuronal lesions from patients with pharmacoresistant focal epilepsies. 766 58

The postnatal development of direct thalamocortical projections from the zona incerta of the ventral thalamus to the whisker representation area of the rat primary somatosensory cortex was investigated. Cytoarchitectonic analysis based on Nissl staining, cytochrome oxidase histochemistry and immunohistochemistry for glutamic acid decarboxylase, GABA, parvalbumin and calbindin D28K revealed that the zona incerta can be clearly distinguished from surrounding diencephalic structures from the day of birth. Moreover, four distinct anatomical subdivisions of this nucleus were identified: the rostral, dorsal, ventral and caudal. Of these, the ventral subdivision is by far the most conspicuous, containing the highest density of neurons, and the highest levels of cytochrome oxidase, glutamate decarboxylase, GABA, parvalbumin and calbindin D28K. In contrast, the dorsal, rostral and caudal subdivisions contain fewer cells, lower levels of glutamic acid decarboxylase and GABA and very few parvalbumin-positive and calbindin-positive neurons. Small injections of rhodamine coated microspheres or Fluoro-gold in the primary somatosensory cortex of animals at different stages of development revealed the existence of retrogradely labeled neurons in the rostral and dorsal subdivisions of the zona incerta from postnatal day 1. At this age, retrogradely labeled cells were also found in the ventral lateral, ventral posterior medial, posterior medial, centrolateral, ventral medial and magnocellular subdivision of the medial geniculate nuclei of the dorsal thalamus. The density of the incertocortical projection reaches its maximum between the first and second postnatal weeks, decreasing subsequently, until an adult pattern of labeling is achieved. Tracer injections combined with immunohistochemistry revealed that the majority of the incertocortical projection derives from GABAergic neurons, implying a potentially inhibitory role for the incertocortical projection. These results demonstrate that the rat trigeminal system contains parallel thalamocortical pathways of opposite polarity, emerging from both the dorsal (glutamatergic, excitatory) and ventral (GABAergic, inhibitory) thalamus since the day of birth. As such, these findings suggest that, contrary to the classical notion, not only the dorsal but also the ventral thalamus may play a special role in both cortical maturation and function.
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PMID:Development of direct GABAergic projections from the zona incerta to the somatosensory cortex of the rat. 777 73

Many septohippocampal neurons are GABAergic and are affected by transection of the fimbria-fornix, like the septohippocampal cholinergic cells. Here we have studied the changes that occur in GABAergic septohippocampal neurons following fimbria-fornix transection. For labeling of septohippocampal projection neurons, adult Sprague-Dawley rats received injections of the fluorescent tracer Fluoro-Gold into the hippocampus 1 week prior to bilateral transection of the fimbria-fornix. After axotomy, rats were allowed to survive for varying periods ranging from 3 weeks to 18 months. Following fixation of the animals, sections through the septal region were either stained by in situ hybridization for glutamate decarboxylase (GAD) mRNA or immunostained for parvalbumin (PARV), which is known to be present in GABAergic septohippocampal neurons. In situ hybridization for GAD mRNA revealed no statistically significant changes in cell number 3 weeks and 6 months postlesion. In contrast, PARV-immunoreactive neurons were reduced to 35% of control 3 weeks postlesion. This value increased to 66% after 6 months of survival. As seen in the electron microscope, axotomized PARV-positive neurons exhibited characteristics of vital cells. Most neurons contained lysosomes associated with Fluoro-Gold, resulting from retrograde labeling prior to fimbria-fornix transection. We conclude that mainly PARV-containing GABAergic neurons in the medial septal nucleus (MS) project to the hippocampus and are thus heavily affected by the lesion but are able to survive and restore the synthesis of PARV. The lack of significant changes in the number of GAD mRNA-expressing cells is explained by the presence of numerous GABAergic MS neurons not projecting to the hippocampus.
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PMID:Fate of GABAergic septohippocampal neurons after fimbria-fornix transection as revealed by in situ hybridization for glutamate decarboxylase mRNA and parvalbumin immunocytochemistry. 857 46


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