Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Huntington's disease is a progressive neurodegenerative disease in which the basal ganglia are preferentially affected. Recent evidence, however, suggests involvement of the cerebral cortex as well, with sparing of neurochemically defined subsets of gamma-aminobutyric acid (GABA)-ergic interneurons. In the present study, we examined changes in concentrations of the amino acid neurotransmitters GABA, glutamate, and aspartate in nine cortical regions from 23 patients with advanced Huntington's disease and 12 control brains. GABA concentrations were significantly increased in eight of the nine regions, consistent with a sparing of GABAergic local circuit neurons in the context of progressive cortical atrophy. Small but significant increases in glutamate were found in six of the nine regions, while aspartate levels were generally unaffected. Striate cortex (Brodmann's area 17) showed the most profound increases in GABA and glutamate. We also investigated the effects of powdering the excitotoxins N-methyl-D-aspartate (NMDA) or kainic acid onto the dura of rats. The resulting lesions were examined at 1 week and 6 months. The NMDA-induced lesions showed striking sparing of parvalbumin-positive neurons (a subset of GABAergic interneurons), and this sparing was reflected in neurochemical measurements of GABA; kainic acid lesions failed to display this selectivity. Somatostatin, cholecystokinin, and vasoactive intestinal polypeptide concentrations were spared by the NMDA-induced lesions, and substance P levels were significantly increased. These results provide evidence that NMDA excitotoxic lesions of cerebral cortex can produce a selective pattern of neuronal damage similar to that which occurs in Huntington's disease.
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PMID:The cortical lesion of Huntington's disease: further neurochemical characterization, and reproduction of some of the histological and neurochemical features by N-methyl-D-aspartate lesions of rat cortex. 128 Sep 37

The GABA neurons of monkey area 17 are a morphologically and chemically heterogeneous population of interneurons that are normally distributed most densely within the geniculocortical recipient zones of the visual cortex. In adult monkeys deprived of visual input from one eye, the levels of immunoreactivity for GABA and GAD within neurons of these geniculocortical zones is reduced. Similar changes are seen in the levels of proteins that make up the GABAA receptor sub-type. The effects of monocular deprivation on other substances suggest that specific types of GABA neurons, such as those in which the tachykinin neuropeptide family and parvalbumin coexist with GABA, are greatly influenced by changes in visual input. That some proteins remain normal within deprived-eye neurons and that other proteins are increased indicates the changes in the GABA cells of the cortex are not the result of a general reduction in protein synthesis. Comparisons of what is known about the morphological and synaptic features of GABA cells in area 17 and the characteristics of cells affected by monocular deprivation suggests that certain classes, such as the clutch cell, may be preferential targets of deprivation. Such a selective loss of certain GABA neurons would have broad implications for the possible physiological plasticity of cortical cells, for if ongoing studies determine that specific receptive field properties are affected by monocular deprivation in adults, the correlation of functional properties and classes of GABA cells would be possible.
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PMID:Organization and plasticity of GABA neurons and receptors in monkey visual cortex. 132 63

Most theories of basal ganglia functions have been based on a model circuit in which the flow of information follows a one-way loop proceeding from the cerebral cortex to the striatum, the pallidum/nigra, the thalamus, and then returns to the cortex. However, this model neglects data from several studies that show a direct feedback projection from the pallidum to the striatum. In this study, we have examined this feedback connection in the ventral striopallidal system to determine the morphology and chemical properties of ventral pallido-striatal projection neurons and to determine the morphology of ventral pallidal efferents in the ventral striatum. Fluoro Gold was injected into the ventral striatum to retrogradely label ventral pallidal projection neurons. Substance P immunoreactivity was used as a pallidal marker to delineate the ventral pallidum. The results show that most neurons retrogradely labeled by Fluoro Gold lie in the ventral pallidum. Additional double-labeling experiments show that none of these Fluoro Gold-labeled cells are cholinergic neurons; however, some are immunoreactive for parvalbumin, a calcium-binding protein found in many pallidal neurons. Electron microscopy revealed that the somata and dendrites of these labeled ventral pallidal projection neurons form many synapses with unlabeled terminals. Injection of Phaseolus vulgaris-leucoagglutinin into the ventral pallidum anterogradely labeled many fibers in the ventral striatum. Electron microscopy revealed that these labeled axons form both symmetric and asymmetric synapses with ventral striatal neurons. We have thus confirmed that there is a significant direct projection from the ventral pallidum to the ventral striatum. Whether this projection forms a part of either monosynaptic or polysynaptic feedback loops remains to be clarified. Nevertheless, this pallidostriatal projection must be integrated into the theories on basal ganglia functions.
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PMID:Ventral pallido-striatal pathway in the rat brain: a light and electron microscopic study. 138 May 22

Fluorescent dextran amines have recently been reported to be useful for anterograde pathway tracing. However, fluorescent markers are not always ideal for detailed mapping studies. We therefore evaluated the efficacy of a biotinylated dextran amine (BDA) for anterograde labeling in several different preparations. BDA was visualized with an avidin-biotinylated HRP (ABC) procedure followed by a standard or metal-enhanced diaminobenzidine (DAB) reaction. After iontophoretic injections of BDA into neocortex-like telencephalic regions in pigeons or into visual or somatosensory cortex in rats, there was excellent and abundant labeling of axons and terminals in forebrain, midbrain and hindbrain target areas with 1-week survival times. Large pressure injections of BDA into the avian telencephalon were also found to result in extensive anterograde labeling. We then carried out a series of studies using 2-color DAB double-labeling to determine effective approaches for combining BDA labeling with other labeling methods. Using an isolated embryonic chick spinal cord-hindlimb preparation, we combined BDA labeling with another anterograde labeling method to differentially label two sets of projections. In these studies, sensory neuron and motoneuron projections into the limb from the same segmental level, or motoneuron projections into the limb from two separate segments were differentially labeled by using HRP (visualized first with a blue/black metal-DAB reaction) and BDA (visualized second with a brown DAB reaction). In other double-labeling studies, we combined BDA labeling of axons and terminals with immunohistochemical labeling of neurons. In these experiments, telencephalic neurons in pigeons or rats were labeled immunohistochemically for parvalbumin or substance P (using a brown DAB reaction) and BDA-labeled axons were labeled blue/black (using a metal-intensified DAB reaction). Double-labeling was successful regardless of whether the entire immunohistochemical labeling procedure preceded or followed the BDA labeling procedure. Together, these studies show that BDA is effective for anterograde pathway tracing and can be used in double-label studies with other labeling methods.
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PMID:Biotinylated dextran amine as an anterograde tracer for single- and double-labeling studies. 138 Oct 34

The superior colliculus is a layered structure in the mammalian midbrain serving multimodal sensorimotor integration. Its intermediate layers are characterized by a compartmental architecture. These compartments are apparent through the clustering of terminals of major collicular afferents, which in many instances match the heterogeneous distribution of tissue components such as acetylcholinesterase, choline acetyltransferase, substance P, and parvalbumin. The present study was undertaken to determine whether efferent cells observe this compartmental architecture. It was found that subpopulations of both descending and ascending collicular efferents originate from perikarya situated in characteristic positions relative to the collicular compartments defined by elevated acetylcholinesterase activity and that their dendrites appear to be specifically coordinated with the heterogeneous environment. With the specific interlocking of afferent and efferent neurons through spatially distinguished neural networks, the compartmental architecture apparently constitutes an essential element for the determination of information flow in the superior colliculus.
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PMID:Association of efferent neurons to the compartmental architecture of the superior colliculus. 143 96

Autopsy study of a patient who died after an episode of prolonged unilateral status epilepticus revealed neuronal loss in the hippocampus on the epileptic side, with gliosis confined to the CA1 and CA3 fields. There was loss of the parvalbumin-immunoreactive gamma-aminobutyric acid (GABA)-ergic interneurons in the hippocampus on that side. There was also loss of the normal laminar pattern of substance P staining with increased substance P immunoreactivity in the supragranular plexus on that side. Met-enkephalin immunoreactivity was also increased in the outer molecular layer of the dentate gyrus on the epileptic side. Mossy fibers on the epileptic side stained more strongly with the Hicks' silver stain and with antibodies against glutamate and taurine, but less intensely with antibodies against calbindin. In the contralateral cerebellum, there was Purkinje cell loss, injury to the remaining Purkinje cells, and increased prominence of the Bergmann glia. Our observations show that prolonged unilateral seizure activity can be associated with specific histochemical changes in the human hippocampus.
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PMID:Neuropathologic asymmetries in the brain of a patient with a unilateral status epilepticus. 171 86

Light and electron microscopic immunohistochemical techniques were used to investigate the central projections and colocalization relationships of a subpopulation of primary afferent neurons that were immunolabelled with an antibody (AB893) against rat liver gap junctions. In lumbar dorsal root ganglia AB893-immunoreactivity was seen in 14.5% of all cells and in both small and large size neurons. Colocalization analysis showed that 78% of all AB893-immunoreactive (AB893-IR) neurons contained calcitonin gene-related peptide, while only 7 to 10% contained the calcium binding proteins parvalbumin or calbindin D28k. Among small type B AB893-IR ganglion cells, it was calculated that over 90% contained fluoride-resistant acid phosphatase, while only 1 to 2% contained substance P or somatostatin. Cytochrome oxidase histochemistry revealed light staining in the vast majority of AB893-IR cells. In the dorsal horn of the spinal cord the antibody labelled fibers in the dorsal root, Lissauer's tract, lamina I and lamina II. Isolated immunoreactive fiber bundles were arranged in sheets spanning most of lamina II. Immunoreactive fibers were depleted from the dorsal horn after dorsal rhizotomy or neonatal capsaicin treatment. Ultrastructural examination showed that AB893-IR fibers were composed of closely associated clusters of 2 to 5 unmyelinated fibers each ranging from 0.1-0.4 microns in diameter. Immunoreactivity was distributed intermittently along the cytoplasmic membrane of axons and en passant sinusoid terminals located centrally within the fiber clusters, as well as along axonal membranes adjacent to the central axon or terminal. The results suggest that the immunoreactive fibers in lamina II of the dorsal horn originate from a subpopulation of AB893-IR neurons that contain FRAP and give rise to unmyelinated axons.
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PMID:Cytochemical relationships and central terminations of a unique population of primary afferent neurons in rat. 193 3

Neurons containing the calcium-binding proteins, calbindin or parvalbumin, were studied by immunohistochemistry in the superficial dorsal horn of the rat spinal cord. Calbindin-containing cells were found in laminae I, II and III, being more abundant in laminae I and II. Some of the neurons in lamina I containing calbindin projected to the supraspinal area. Parvalbumin-containing neurons were mainly distributed in laminae IIi and III. Calbindin and parvalbumin were not detected in the same cells. Some 75% of the neurotensin-like immunoreactive neurons contained calbindin, which corresponded to 13% of the calbindin-containing neurons. Calbindin was sometimes found in the same cells with substance P, enkephalin or somatostatin but less frequently (44-46% of the peptide-containing neurons). Parvalbumin was not found together with these peptides. Electron microscopy showed that the immunoreactive products of calbindin or parvalbumin were mostly in the dendrites or cell bodies. Immunoreactive axon terminals were relatively few. In rhizotomized animals, neurons containing one of these proteins in laminae II and III were found to receive direct inputs of primary afferent fibers. These findings indicate that neurons containing these two proteins belong to different subpopulations of dorsal horn neurons. They may be important in primary afferent processing.
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PMID:Calcium-binding proteins calbindin and parvalbumin in the superficial dorsal horn of the rat spinal cord. 224 26

Counts performed on dissociated cell cultures of E10 chick embryo dorsal root ganglia (DRG) showed after 4-6 days of culture a pronounced decline of the neuronal population in neuron-enriched cultures and a net gain in the number of ganglion cells in mixed DRG cell cultures (containing both neurons and nonneuronal cells). In the latter case, the increase in the number of neurons was found to depend on NGF and to average 119% in defined medium or 129% in horse serum-supplemented medium after 6 days of culture. The lack of [3H]thymidine incorporation into the neuronal population indicated that the newly formed ganglion cells were not generated by proliferation. On the contrary, the differentiation of postmitotic neuroblasts present in the nonneuronal cell compartment was supported by sequential microphotographs of selected fields taken every hour for 48-55 hr after 3 days of culture. Apparently nonneuronal flat dark cells exhibited morphological changes and gradually evolved into neuronal ovoid and refringent cell bodies with expanding neurites. The ultrastructural organization of these evolving cells corresponded to that of primitive or intermediate neuroblasts. The neuronal nature of these rounding up cell bodies was indeed confirmed by the progressive expression of various neuronal cell markers (150 and 200-kDa neurofilament triplets, neuron specific enolase, and D2/N-CAM). Besides a constant lack of immunoreactivity for tyrosine hydroxylase, somatostatin, parvalbumin, and calbindin-D 28K and a lack of cytoenzymatic activity for carbonic anhydrase, all the newly produced neurons expressed three main phenotypic characteristics: a small cell body, a strong immunoreactivity to MAG, and substance P. Hence, ganglion cells newly differentiated in culture would meet characteristics ascribed to small B sensory neurons and more specifically to a subpopulation of ganglion cells containing substance P-immunoreactive material.
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PMID:Differentiation of postmitotic neuroblasts into substance P-immunoreactive sensory neurons in dissociated cultures of chick dorsal root ganglion. 243 96

Neurotrophin-3-deficient (NT-3-deficient) mice were generated by gene targeting. Mutant mice displayed severe movement defects of the limbs, and most died shortly after birth. Substantial portions of peripheral sensory and sympathetic neurons were lost while motor neurons were not affected. Significantly, spinal proprioceptive afferents and their peripheral sense organs (muscle spindles and Golgi tendon organs) were completely absent in homozygous mutant mice. This correlated with a loss of parvalbumin and carbonic anhydrase-positive neurons in the dorsal root ganglion. No gross abnormalities were seen in Pacinian corpuscles, cutaneous afferents containing substance P and calcitonin gene-related peptide, and deep nerve fibers in the joint capsule and tendon. Importantly, the number of muscle spindles in heterozygous mutant mice was half of that in control mice, indicating that NT-3 is present at limiting concentrations in the embryo.
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PMID:Lack of neurotrophin-3 leads to deficiencies in the peripheral nervous system and loss of limb proprioceptive afferents. 751 2


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