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

Parvalbumin (PV)-immunoreactive neurons in rat neostriatum were studied under light and electron microscopes. A small number of neurons in the striatum were immunoreactive for PV (a Ca-binding protein). Most of them were also strongly immunoreactive for glutamate decarboxylase but were negative for NADPH-diaphorase activity. Light microscopic analysis revealed that PV-containing neurons have somata with fusiform or polygonal shape and are medium to large in size. The dendrites were smooth and cylindrical at the proximal portion but were varicose at the distal portion. Thin PV-immunoreactive fibers with large boutons were unevenly distributed in the striatum. Electron microscopy revealed that the somata of PV-immunoreactive neurons had a deeply indented nucleus with a nucleolus and often an intranuclear rod. These are the morphological features reported for interneurons of the striatum. Gap junctions formed between two neighboring PV-immunoreactive dendrites. A total of 175 boutons forming synapses with somata and dendrites of PV-immunoreactive neurons were examined. Of these, 115 were small in diameter (less than 1 micron), contained densely packed round vesicles and formed asymmetrical synapses mainly with dendrites. The other 60 boutons formed symmetrical synapses with somata and dendrites of PV-immunoreactive neurons. Both myelinated and unmyelinated axons with boutons were observed. PV-immunoreactive boutons had a diameter of 0.3-2 microns and contained round or elongated vesicles which were about 35 nm in diameter. The boutons formed symmetrical synapses with postsynaptic targets. Of the 100 PV-immunoreactive boutons, 51 were found on somata and proximal dendrites of medium-sized neurons containing a large, round, centrally located nucleus. The others formed synapses with dendrites of various sizes. It was occasionally observed that varicose dendrites free of spines were contacted by a large number of PV-immunoreactive boutons. The study indicates that, in the striatum, immunocytochemistry for PV selectively stains GABAergic interneurons and that the GABAergic interneurons are incorporated in a feed-forward inhibitory circuit of the striatum.
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PMID:Parvalbumin-immunoreactive neurons in the rat neostriatum: a light and electron microscopic study. 208 40

The possible coexistence of the calcium-binding protein, parvalbumin, with the major inhibitory neurotransmitter, gamma-aminobutyric acid (GABA), and its synthesizing enzyme, glutamate decarboxylase (GAD), was studied in nonpyramidal cells of the rat medial and lateral entorhinal cortex. The material was analyzed by two different methods, the first of which was a mirror techniques where the possible coexistence of two different antigens was analyzed from cells cut in half at the surface of the adjacent section. The other method consisted of analyzing double immunofluorescent-stained sections with a confocal microscope. The colocalization analysis revealed that all parvalbumin-immunoreactive neurons (mirror technique n = 688 and confocal microscopy n = 644) in all layers of the medial and lateral entorhinal cortex were also immunopositive for GABA or GAD. Parvalbumin-cells made up 52% of the GABA cells in most of the layers in the medial and lateral entorhinal cortex. In layer III of the entorhinal cortex, the proportion was about 40%. Thus, parvalbumin-containing neurons in the entorhinal cortex represent a large GABAergic cell population, which is likely to play an important role in controlling both the input and the output of the entorhinal cortex.
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PMID:Coexistence of parvalbumin and GABA in nonpyramidal neurons of the rat entorhinal cortex. 872 Apr 98

Cortical interneurons are classified into several subtypes that contribute to cortical oscillatory activity. Parvalbumin (PV)-expressing cells, a type of inhibitory interneuron, are involved in the gamma oscillations of local field potentials (LFPs). Under ketamine-xylazine anesthesia or sleep, mammalian cortical circuits exhibit slow oscillations in which the active-up state and silent-down state alternate at ~1 Hz. The up state is composed of various high-frequency oscillations, including gamma oscillations. However, it is unclear how PV cells and somatostatin (SOM) cells contribute to the slow oscillations and the high-frequency oscillations nested in the up state. To address these questions, we used mice lacking glutamate decarboxylase 67, primarily in PV cells (PV-GAD67 mice) or in SOM cells (SOM-GAD67 mice). We then compared LFPs between PV-GAD67 mice and SOM-GAD67 mice. PV cells target the proximal regions of pyramidal cells, whereas SOM cells are dendrite-preferring interneurons. We found that the up state was shortened in duration in the PV-GAD67 mice, but tended to be longer in SOM-GAD67 mice. Firing rate tended to increase in PV-GAD67 mice, but tended to decrease in SOM-GAD67 mice. We also found that delta oscillations tended to increase in SOM-GAD67 mice, but tended to decrease in PV-GAD67 mice. Current source density and wavelet analyses were performed to determine the depth profiles of various high-frequency oscillations. High gamma and ripple (60-200 Hz) power decreased in the neocortical upper layers specifically in PV-GAD67 mice, but not in SOM-GAD67. In addition, beta power (15-30 Hz) increased in the deep layers, specifically in PV-GAD67 mice. These results suggest that PV cells play important roles in persistence of the up state and in the balance between gamma and beta bands across cortical layers, whereas SOM and PV cells may make an asymmetric contribution to regulate up-state and delta oscillations.
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PMID:Contribution of parvalbumin and somatostatin-expressing GABAergic neurons to slow oscillations and the balance in beta-gamma oscillations across cortical layers. 2569 59

Treatment strategies for ischemic stroke are still limited, since numerous attempts were successful only in preclinical research but failed under clinical condition. To overcome this translational roadblock, clinical relevant stroke models should consider co-morbidities, age-related effects and the complex neurovascular unit (NVU) concept. The NVU includes neurons, vessels and glial cells with astrocytic endfeet in close relation to the extracellular matrix (ECM). However, the role of the ECM after stroke-related tissue damage is poorly understood and mostly neglected for treatment strategies. This study is focused on alterations of perineuronal nets (PNs) as ECM constituents and parvalbumin-containing GABAergic neurons in mice with emphasis on the nucleus reticularis thalami (NRT) in close proximity to the ischemic lesion as induced by a filament-based stroke model. One day after ischemia onset, immunofluorescence-based quantitative analyses revealed drastically declined PNs in the ischemia-affected NRT from 3- and 12-month-old wildtype and co-morbid triple-transgenic (3xTg) mice with Alzheimer-like alterations. Parvalbumin-positive cells decreased numerically in the ischemia-affected NRT, while staining intensity did not differ between the affected and non-affected hemisphere. Additional qualitative analyses demonstrated ischemia-induced loss of PNs and allocated neuropil ECM immunoreactive for aggrecan and neurocan, and impaired immunoreactivity for calbindin, the potassium channel subunit Kv3.1b and the glutamate decarboxylase isoforms GAD65 and GAD67 in the NRT. In conclusion, these data confirm PNs as highly sensitive constituents of the ECM along with impaired neuronal integrity of GABAergic neurons. Therefore, specific targeting of ECM components might appear as a promising strategy for future treatment strategies in stroke.
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PMID:Abolished perineuronal nets and altered parvalbumin-immunoreactivity in the nucleus reticularis thalami of wildtype and 3xTg mice after experimental stroke. 2763 71

We immunohistochemically characterized postnatal changes in cerebellar cortical cytoarchitectures in ferrets using markers for cerebellar cortical neurons and glial cells. Although 10 lobules of the vermis were already observed on postnatal day (PD) 4, Purkinje cells were still arrayed into two to three layers. Purkinje cells were aligned in a monolayer by PD 10 and formed mature shapes on PD 42 by developing their dendritic arbors. Parvalbumin immunostaining revealed relatively slower maturation of Purkinje cells in the Lobule X cortex than in other lobules. Basket and stellate cells emerged in the molecular layer on PDs 21 and 42, respectively. Rosette-like arranged glutamate decarboxylase 65 and 67-positive puncta were observed in the inner granular layer (IGL) on PD 21. Proliferating cell nuclear antigen immunostaining appeared in the outer zone of the external granular layer (EGL) containing progenitors of granular neurons on PDs 4-21. Bergmann glial processes extending vertically through the molecular layer and EGL were visible with GFAP immunostaining on PD 10 and thereafter. Their somata, aligned in the Purkinje cell layer, showed immunopositivity to Sox2 already on PD 4 and subsequently to S100 protein on PD 10. Sox2-positive cells were found sparsely in the IGL. Few of them were NeuN positive on PD 90, predicting the possibility of adult neurogenesis. These immunohistochemical results revealed that ferrets underwent cerebellar cortical histogenesis during their postnatal life in sequences. Relatively slow development or maturation of the ferret cerebellum was revealed by the timing of the monolayer alignment and morphological maturation of Purkinje cells.
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PMID:Immunohistochemical characterization of postnatal changes in cerebellar cortical cytoarchitectures in ferrets. 3239 12