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)

The dorsal raphe nucleus (DR) harbours the largest single collection of serotonin (5-HT)-containing neurons in the brain but also comprises other types of chemospecific neurons. The aim of the present study was to characterise morphologically and immunohistochemically the DR in the squirrel monkey (Saimiri sciureus). The morphology of the DR 5-HT-immunoreactive (ir) neurons was analysed and their distribution compared to that of neurons displaying immunoreactivity for either tyrosine hydroxylase (TH), gamma-aminobutyric acid (GABA), substance P (SP), calbindin-D28k (CB), calretinin (CR) or parvalbumin (PV). The 5-HT-ir neurons were distributed in a highly heterogeneous manner throughout the rostrocaudal extent of the DR. The morphology and density of the 5-HT neurons were found to vary significantly in the major subdivisions of the primate DR, that is, the median, ventral, dorsal, ventrolateral, lateral and caudal subnuclei. Numerous SP-, GABA- and PV-ir neurons occurred in all six subnuclei of the DR. The distribution of SP-ir neurons was largely in register with that of 5-HT-ir neurons. Neurons expressing the other neuronal markers (TH, CB, CR) were not present in all six DR subnuclei and their distribution was either complementary to, or in register with, that of 5-HT-ir neurons. The median subnucleus was unique because it contained all the different types of chemospecific neurons. This study has revealed that the primate DR is chemically highly heterogeneous, a finding that may explain the multifarious influence that this nucleus exerts upon various forebrain structures.
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PMID:Chemoarchitecture of the primate dorsal raphe nucleus. 971 63

Peptidergic innervation and localization of the neuronal nicotinic acetylcholine receptor (nAChR) was studied in the basal forebrain of Macaca fascicularis in order to provide microstructural proofs for the theory (Changeux et al., 1992) that calcitonin gene-related peptide (CGRP) is responsible for the maintenance of the acetylcholine receptor. Distribution and localization of five neuropeptides, namely substance P (SP), CGRP, neuropeptide Y (NPY), vasoactive intestinal polypeptide (VIP) neurotensin (NT), and the neuropeptides parvalbumin (PV) and the alpha-bungarotoxin- (alpha-BTX-) binding protein was studied by means of light- and electron microscopic pre-embedding immunocytochemistry. Immunohistochemical double staining revealed that large cholinergic principal nerve cells in the basal forebrain, corresponding to cell group Ch4 constituting Meynert's basal nucleus (BNM), and exerting intense choline acetyltransferase (ChAT) immunoreactivity, are synaptically innervated by axons displaying CGRP immunoreactivity. While SP, NPY, PV and CGRP establish dense networks in BNM, innervation by NT and VIP is sparse. Biotinylated alpha-BTX visualizes beaded axons that surround dendrites and perikarya of cholinergic principal cells. Electron microscopic organization of the neuropil in BNM is characterized by a glomerular (or rather cartridge-like) arrangement of axons surrounding dendrites of non-cholinergic principal nerve cells. At least one of the axons establishing the glomerulus (cartridge) exerts CGRP immunopositivity while alpha-BTX-immunopositive axons, presynaptic to dendrites of principal cells, are attached to the glomeruli (cartridges) from outside. As alpha-BTX-binding indicates localization of the alpha7 subunit of the neuronal nAChR, the microtopographical arrangement supports the idea that, in a manner similar to that in the neuromuscular junction, CGRP might contribute to the maintenance of nAChR also in BNM. Our results suggest that presynaptic nAChR-s are involved in the regulation of acetylcholine release from a feed-forward amplification mechanism of cholinergic principal cells of BNM.
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PMID:Peptidergic innervation and the nicotinic acetylcholine receptor in the primate basal nucleus. 974 20

NMDA receptors are composed of proteins from two families: NMDAR1 and NMDAR2. We used quantitative double-label in situ hybridization to examine in rat brain the expression of NMDAR1, NMDAR2A, NMDAR2B, and NMDAR2C mRNA in six neurochemically defined populations of striatal neurons: preproenkephalin (ENK) and preprotachykinin (SP) expressing projection neurons, and somatostatin (SOM), glutamic acid decarboxylase 67 (GAD67), parvalbumin (PARV), and choline acetyltransferase (ChAT) expressing interneurons. NMDAR1 was expressed by all striatal neurons: strongly in ENK, SP, PARV and ChAT neurons, and less intensely in SOM and GAD67 positive cells. NMDAR2A mRNA was present at moderate levels in all striatal neurons except those containing ChAT. Labeling for NMDAR2B was strong in projection neurons and ChAT interneurons, and only moderate in SOM, GAD67 and PARV interneurons. NMDAR2C was scarce in striatal neurons, but a low level signal was detected in GAD67 positive cells. NMDAR2C expression was also observed in small cells not labeled by any of the markers, most likely glia. These data suggest that all striatal neurons have NMDA receptors, but different populations have different subunit compositions which may affect function as well as selective vulnerability.
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PMID:Expression of NMDA glutamate receptor subunit mRNAs in neurochemically identified projection and interneurons in the striatum of the rat. 988

Development of glomerular synapses in the superficial dorsal horn has been studied in the embryonic macaque spinal cord using light and electron microscopic techniques including Golgi impregnation, 3H-thymidine radioautography and pre-embedding immunohistochemistry of substance P (SP), calcitonin gene related peptide (CGRP), calbindin D-28 K (CB) and parvalbumin (PV). The study revealed that substantia gelatinosa cells of the primate dorsal horn are generated last, but unlike in rodents, synaptogenesis in this region starts at early embryonic (E) stages of the 165-day long gestation. Already by E30, both Type 1 (light) and 2 (dark) dorsal root axons and their growth cones are identifiable within the oval bundle of His, before they form synaptic contact with their final target cells. Subsequently they invade the dorsal horn and enter the bisecting interfaces formed by orderly programmed cell death. Each type of scalloped (sinusoid) central primary afferent terminal (i.e. DSA, RSV and LDCV) have well defined pre- and post-synaptic specializations already by E40. Among the neuropeptides studied, SP appears first at E67 and CGRP at E70 in the lateral position but within a few days both of them are spread to the entire superficial dorsal horn. Both SP and CGRP are present in the thin dorsal root axons and their growth cones, giving rise to scalloped and simple axon terminals. PV is transiently present in the entire length of the thick dorsal root afferents before becoming concentrated in the synaptic boutons. CB is displayed mainly in neurons of the lamina I and III. Dendrites of CB-immunoreactive cells establish synaptic connection with each type of dorsal root afferents, including glomerular synaptic complexes. These data reveal that the superficial dorsal horn in the primate spinal cord develops its characteristic synaptic complexes much earlier in gestation than in any other mammalian species studied. Furthermore, characteristic cytological features of the prospective glomerular complex emerge before establishment of the final synaptic contacts.
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PMID:Development of glomerular synaptic complexes and immunohistochemical differentiation in the superficial dorsal horn of the embryonic primate spinal cord. 993 Jun 20

The present study evaluates the cytoarchitecture of midbrain dopaminergic regions in baboons using similar methodology to that recently applied to compare humans and rats. This information is relevant for the interpretation of nonhuman primate models of Parkinson's disease (PD). The midbrains of four alpha male baboons were serially sectioned into 10 evenly spaced series of 50 microm sections. Series were stained with either cresyl violet or immunohistochemically reacted for tyrosine hydroxylase, substance P, calbindin-D28k, or parvalbumin. The organization of dopaminergic cell groups and the distribution of proteins within these groups were found to be very similar to that previously described in humans [McRitchie et al., J. Comp. Neurol. 364:121-150; 1996]. Dorsal and ventral tiers of the A9 substantia nigra (SN) pars compacta and all divisions of the A8 and A10 cell groups were identified revealing a high degree of homology in the arrangement of chemically distinct midbrain neurons between primates. The major difference between the organization of human and baboon midbrain dopaminergic neurons is the anteroposterior extent of the dense cell clusters within the SN pars compacta. In baboons the dorsomedial cell cluster is absent at posterior levels. The ventral tier cell clusters, which are targeted by PD in humans, are restricted to the posterior and ventral regions of the SN pars compacta of the baboon. In humans these cell clusters are found throughout the rostrocaudal extent of the SN. These ventral cell clusters have been previously shown to have reciprocal connections with sensorimotor regions of the putamen.
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PMID:The midbrain dopaminergic cell groups in the baboon Papio ursinus. 1007 18

Animal experiments have already shown that neurotransmitters and neuropeptides are not only important for normal functioning of the adult central nervous system (CNS) but are also crucial to its development. However, information on the spatio-temporal distribution of these endogenous substances in the developing human CNS is still scarce. With the use of immunocytochemical staining and a constant supply of properly fixed human abortuses from southern China, an early appearance of acetylcholinesterase, enkephalin, and substance P immunoreactivities was detected first in the spinal cord (weeks 5 to 7 of gestation), then in the brainstem nuclei (weeks 11 to 12). Their overlapping localizations in many regions of the CNS suggest possible interactions among neurons containing these substances, which are in turn important for the proper establishment of the neuronal circuitry. Immunoreactivity for neuropeptide Y appeared initially in the lateral region of upper segments of the spinal cord at week 12 of gestation, then spread latero-medially and cranio-caudally to the sacral region. In the hippocampus, neuropeptide Y neurons appeared from week 15 onwards. Serotoninergic neurons were found in the dorsal raphe nucleus at week 10 and then decreased in number as the fetus grew older. Somatostatin releasing inhibitory factor, vasopressin, and oxytocin were detected in the hypothalamus from weeks 12 to 14 onwards, and monoamine oxidase, succinic dehydrogenase, parvalbumin, calbindin D28K, and vasoactive intestinal peptide were found in the visual cortex at midgestation. The early appearance and the abundance of the neurotransmitters and neuropeptides in the developing CNS indicate that they may play a key role in neuronal differentiation.
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PMID:Early appearance of acetylcholinergic, serotoninergic, and peptidergic neurons and fibers in the developing human central nervous system. 1040 66

The neurochemical organization of the striosomal compartment in the human striatum was analyzed by histochemical and immunohistochemical techniques applied to postmortem tissue from normal individuals. The striosomes were delineated by using the following markers: acetylcholinesterase (AChE), enkephalin (ENK), substance P (SP), calbindin-D28k (CB), parvalbumin (PV), calretinin (CR), limbic system-associated membrane protein (LAMP), choline acetyltransferase (ChAT), tyrosine hydroxylase (TH), and NADPH-diaphorase. Comparisons were made between striosomal boundaries, as outlined by each marker applied on adjacent sections, and particular attention was paid to possible variations in the chemical features of striosomes along the rostrocaudal extent of the striatum. The main findings of this study are as follows: 1) the striosomal compartment is composed of two chemically distinct domains: a core and a peripheral region; 2) the core is largely devoid of CB and displays a less intense staining for ENK and LAMP than the peripheral region; 3) although striosomes are largely devoid of AChE, the activity of this enzyme is slightly higher in the core than in the peripheral region; 4) the core and peripheral regions are weakly stained for PV and intensely stained for SP; 5) ChAT-, CR- and NADPH-diaphorase-positive neurons are preferentially distributed in the peripheral region; 6) at rostral striatal levels, striosomes are largely devoid of TH, whereas the inverse is true caudally; and 7) at caudal striatal levels, the peripheral region of striosomes is intensely stained for CB and ChAT. These results demonstrate that the striosomes in human display a strikingly complex and heterogeneous chemical architecture.
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PMID:Chemical heterogeneity of the striosomal compartment in the human striatum. 1049 46

Caldendrin is a novel calcium-binding protein confined to the somatodendritic compartment of neurons. Here we have studied the expression pattern of caldendrin in the rat retina. First we assessed the distribution of caldendrin transcripts in the adult and developing retina by in situ hybridization. In the adult retina, transcripts are expressed mainly in the inner half of the inner nuclear layer (INL) and to a lesser extent in the ganglion cell layer (GCL). During development labeling of the inner part of the cytoblast layer, where amacrine cells reside, is already present at postnatal day 1 (P1). The intensity of hybridization signal in this sublamina of the developing INL increases up to P8, whereas significant labeling in the GCL was first found at P14, coinciding with eye opening. Immunodetection with a polyclonal antibody revealed intensive staining of cells in the inner retina, which are presumably mainly amacrine and significantly fewer bipolar and ganglion cells. All parvalbumin-containing All amacrines were immunopositive for caldendrin. Colocalization with calbindin was found in cone bipolar cells, the majority of AII amacrines, and calbindin-positive cells in the GCL. In the GCL, caldendrin was also colocalized with calretinin-immunopositive cells. Most caldendrin-positive amacrine cells in the adult rat retina were glycinergic and only a few were GABAergic. In retinal flat mounts, it was confirmed that less than 10% of retrogradely labeled retinal ganglion cells (RGC) are caldendrin-positive. Caldendrin immunoreactivity does not colocalize with tyrosine hydroxylase, VIP, substance P and somatostatin immunoreactivity. In summary, caldendrin expression is regulated differentially in retinal cell types during development and is restricted to a subpopulation of amacrine, bipolar, and ganglion cells, suggesting specific functions in the developing and mature retina.
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PMID:The cytoskeleton-associated neuronal calcium-binding protein caldendrin is expressed in a subset of amacrine, bipolar and ganglion cells of the rat retina. 1055 36

Huntington's disease is a devastating progressive neurodegenerative illness characterized by massive neuronal loss in the striatum. It is caused by the presence of an expanded CAG repeat in the gene encoding huntingtin, a protein of unknown function. We have examined the expression of neurotransmitters and other antigens present in striatal neurons with immunohistochemistry, and the level of expression of mRNAs encoding enkephalin, substance P, and glutamic acid decarboxylases with quantitative in situ hybridization histochemistry, in the striatum of two mouse models of Huntington's disease: transgenic animals expressing exon 1 of the human huntingtin gene with 144 CAG repeats and "knock-in" mice containing a chimeric mouse/human exon 1 with 71 or 94 CAG repeats inserted by homologous targeting. Although the transgenic (but not the knock-in) mice were previously shown to display prominent huntingtin- and ubiquitin-containing nuclear inclusions in striatal neurons, in situ nick translation followed by emulsion autoradiography did not reveal any DNA damage in striatum or cortex in these mice. Immunolabeling for calbindin D 28K, enkephalin, substance P, glutamic acid decarboxylases (M(r) 65,000 or 67,000, GAD65 and GAD67), somatostatin, choline acetyltransferase, parvalbumin, and glial fibrillary acidic protein were remarkably similar in transgenic, knock-in, and wild-type mice. Both transgenic and knock-in mice, however, showed a marked decrease in the level of expression of enkephalin mRNA in striatal neurons without significant decreases in mRNAs encoding substance P, GAD65, or GAD67. The data indicate that decreased expression of enkephalin mRNA may be an early sign of neuronal dysfunction due to the Huntington's disease mutation.
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PMID:Decrease in striatal enkephalin mRNA in mouse models of Huntington's disease. 1073 39

Calretinin (CR) is a calcium-binding protein purported to have neuroprotective properties. This study was designed to characterize the types of neurons containing CR in two different primary cultures and to determine which, if any, CR-immunoreactive (CR-ir) neurons are resistant to excitotoxic insults. Calretinin-containing neurons in cortical primary cultures derived from E14 rat embryos were not resistant to either kainic acid or a brief calcium overload induced by the calcium ionophore A23187. Equal proportions of CR-ir and GABAergic cortical neurons were lost after a 24-h exposure to 100 or 500 microM kainic acid. A 3 microM, 3-h exposure to A23187 induced equivalent amounts of cell loss in both the total cell and CR-ir cortical neuron culture populations. Cortical cultures grown for 6-7 days were more vulnerable than 12- to 13-day-old cultures to short-term, low-concentration treatments of A23187. Older cultures, however, were more severely affected when examined 24 h after a 3-h exposure to A23187. Calretinin-immunoreactive neurons derived from the diencephalon were relatively more resistant than cortical neurons to kainic acid at 6-7 days in vitro. In cortical or diencephalic cultures, CR was rarely coexpressed with GABA or calbindin D-28k. No vasoactive intestinal peptide, substance P, or parvalbumin was detected in CR-ir neurons in either culture system. We suggest that the presence of CR alone is not sufficient to spare neurons from a toxic calcium overload. Calretinin may still buffer calcium at low concentrations or be a component in a calcium-based signal transduction system.
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PMID:Vulnerability to calcium-induced neurotoxicity in cultured neurons expressing calretinin. 1083 5


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