UNIPROT:P61278 - FACTA Search

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Material for the study came from one 126 day-old rhesus monkey fetus and two 3 day-old neonates. The immunocytochemical detection of somatostatin, neurotensin (NT), parvalbumin, calbindin D-28K, DARPP-32 as well as tyrosine hydroxylase (TH), dopamine-beta-hydroxylase and serotonin (5-HT), was carried out on serial cryostat sections of the entorhinal cortex. The authors reported in a previous paper the precocious differentiation of the entorhinal cortex in rhesus monkey fetuses and featured the conspicuous expression of calbindin D-28K, somatostatin, neurotensin, and the monoaminergic innervation during the first half of gestation. The present study shows distinct temporal profiles of neurochemical development during the second half of gestation: the dense neuropeptidergic innervation remained a constant feature; the three aminergic systems gradually increased in density; parvalbumin, unlike calbindin D-28K, was primarily expressed during the last quarter of gestation. Three other prominent features of the last quarter of gestation are illustrated: the refinement of the modular neurochemical organization of the lamina principalis externa, the delayed chemoanatomical development of the rhinal sulcus area, and the establishment of a distinct rostrocaudal pattern of neurochemical distribution. In correspondence with the cluster-like organization of the lamina principalis externa, the authors observed in the olfactory, rostral, and intermediate fields of the neonate monkey entorhinal cortex, a particular subset of pyramidal-shaped neurons: located in layer III, they were characterized by fasciculated apical dendrites ascending between the cellular islands of the discontinuous layer II and the coexpression of calbindin D-28K and DARPP-32. Besides, most of the other chemical systems displayed a distinct, area-specific, patchy distribution, except for the homogeneously distributed noradrenergic innervation. In the olfactory and rostral fields, TH positive dopaminergic fibers accumulated on the neuronal islands of layers II-III, and parvalbumin labeled fibers on those of layer III, whereas patches of 5-HT and NT-like reactive terminals were segregated between the cellular islands, overlapping the DARPP-32/calbindin D-28 K labeled dendritic bundles. At the opposite, in the intermediate field, 5-HT positive terminals overlapped the cellular islands of layer II and thin fascicles of dopaminergic fibers ran in the inter island spaces. The somatostatin-LIR innervation was apparently too dense to reveal a patchy distribution that existed at earlier developmental stages. In the caudal field, the patchy pattern was replaced by a predominant bilaminar type of distribution of NT, 5-HT, and TH-like positive afferents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurochemical development of the hippocampal region in the fetal rhesus monkey. II. Immunocytochemistry of peptides, calcium-binding proteins, DARPP-32, and monoamine innervation in the entorhinal cortex by the end of gestation. 791 99

Although the entorhinal cortex is a key structure connecting the hippocampal formation with the rest of the cerebral cortex, little is known about its early chemoanatomical development in primates. In the present study, a cytoarchitectonic analysis and immunocytochemical detection of somatostatin, neurotensin, parvalbumin, calbindin-D 28K, DARPP-32, as well as tyrosine hydroxylase, dopamine-beta-hydroxylase, and serotonin, were carried out on serial sections of the entorhinal cortex of six rhesus monkey fetuses aged E47 to E90 (gestation period 165 days). At E56 the cortical plate of the entorhinal cortex already exhibited a sublamination; at E64 the lamina dissecans was partly formed, allowing the emergence of the lamina principalis externa and interna, and at E83 most of the regional and laminar subdivisions characteristic of the adult cortex could be identified, except for the rhinal sulcus restricted to a small dimple. The neurochemical development paralleled the early cytoarchitectonic differentiation, both largely preceding that of the neighboring cortical areas. The somatostatin-like immunoreactive innervation, first detected at E56, was very dense as early as E64 and displayed by E83 a laminar distribution similar to that found in the adult. Labeled neurons indicated an intrinsic origin for this innervation but an extrinsic connection might be present as labeled fibers in the subplate of the entorhinal cortex were in continuity with positive fibers in the intermediate zone of the hippocampal formation. A faint neurotensin-like immunoreactivity first detected at E64 became prominent at E83 in the entorhinal cortex but stopped abruptly at the anlage of the rhinal sulcus. The lack of neurotensin-labeled neurons contrasted with their presence in other parts of the hippocampal region and suggested a precocious extrinsic connection. Only rare parvalbumin-LIR neurons were detected at midgestation, whereas calbindin-D 28K was expressed from E47 on in Cajal-Retzius cells and from E56 on in various types of neurons in the cortical plate and subplate. Most characteristic was a category of medium-sized, deeply stained calbindin-LIR neurons, present only in the lamina principalis externa and possibly corresponding to the population of large neurons described by Kostovic et al. (1990, Soc Neurosci Abstr 16:846) in early developing entorhinal cortex of human fetuses. These and probably other neurons were also DARPP-32-positive, suggesting the possibility of an early dopaminergic regulation. Indeed, the monoaminergic innervation of the entorhinal cortex was detected from E56 on and gradually increased in density, displaying areal and laminar differences in the distribution of the dopaminergic, noradrenergic, and serotoninergic afferents.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Neurochemical development of the hippocampal region in the fetal rhesus monkey. I. Early appearance of peptides, calcium-binding proteins, DARPP-32, and monoamine innervation in the entorhinal cortex during the first half of gestation (E47 to E90). 835 10

Previous studies have reported the presence of the calcium binding protein calretinin in neurons in the striatal part of the basal ganglia in rats and primates. In the present study, immunofluorescence double-labeling techniques and immunofluorescence combined with retrograde labeling were used in rats to determine whether calretinin is found in any of the known types of striatal neurons. The results showed that a small fraction of the calretinin-containing neurons (< 10%) contain parvalbumin, but none of the calretinin-containing striatal neurons contained markers for the other two major types of striatal interneurons (i.e., choline acetyltransferase-containing cholinergic neurons and somatostatin-containing neurons). Additionally, calretinin was not found in projection neurons, using either calbindin or DARPP32 as immunofluorescent markers of striatal projections neurons in general, or using retrograde labeling to specifically identify either striatonigral or striatopallidal neurons. Thus, calretinin appears to be largely found in a unique population of striatal interneurons in rats. This population appears to be about one third the abundance of any of the previously identified populations of striatal interneurons.
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PMID:Calretinin is largely localized to a unique population of striatal interneurons in rats. 886 67

Developmental changes of the distribution pattern of substance P receptor (SPR) were investigated immunohistochemically in the rat striatum. The SPR immunoreactivity in the striatum first emerged at postnatal day 1 and transiently showed a patchy pattern of distribution until it displayed the adult pattern of homogeneous distribution by the third postnatal week. The SPR-immunoreactivity patches were most marked in the medial and dorsolateral parts of the striatum, as well as in the subcallosal streak. They matched tyrosine hydroxylase-enriched areas and, conversely, avoided calbindin-enriched zones. No neurons within the SPR-immunoreactive patches contained either choline acetyltransferase or somatostatin, which is known to be contained in intrinsic neurons in the striatum. The vast majority of SPR-immunoreactive patch neurons also contained DARPP-32, a phosphoprotein that is expressed in striatal projection neurons with D1 dopamine receptor. The results indicate that SPR-immunoreactive patches which appear transiently in the developing striatum are in register with the striatal patch compartment, and that SPR immunoreactivity within these patches may be expressed on projection neurons rather than intrinsic neurons. Such SPR immunoreactivity in projection neurons in striatal patches may fade out in adulthood.
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PMID:Patchy distribution of substance P receptor immunoreactivity in the' developing rat striatum. 887 81

The striatum is thought to be generated from two transient swellings in the ventral telencephalon, the lateral and medial ganglionic eminences, present at mid-stages of embryonic rat development. We have studied the relative contribution of these structures to the specific generation of striatal neuronal subtypes such as projection neurons and cholinergic and somatostatin-containing interneurons at an early stage and a mid stage in striatal neurogenesis. Dissociated progenitors isolated from the embryonic day 12.5 and embryonic day 15.5 rat lateral ganglionic eminence grafted into the previously ibotenic acid lesioned adult striatum, produce grafts containing extensive numbers of neurons expressing messenger RNA for the striatal projection neuron marker, DARPP-32, whereas grafts of the embryonic day 12.5 and embryonic day 15.5 medial ganglionic eminences do not. While preprosomatostatin messenger RNA-expressing neurons were observed in grafts from each of the lateral ganglionic eminence and medial ganglionic eminence at both embryonic day 12.5 and embryonic day 15.5, choline acetyltransferase messenger RNA-expressing cholinergic neurons were largely found in grafts derived from the embryonic day 12.5 medial ganglionic eminence. These results suggest that the neuronal diversity of the adult striatum may derive both from the lateral ganglionic eminence, providing DARPP-32-expressing projection neurons as well as somatostatin-containing interneurons, and the early stage medial ganglionic eminence specifically contributing the cholinergic interneurons.
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PMID:Early specification of striatal projection neurons and interneuronal subtypes in the lateral and medial ganglionic eminence. 957 90

Intrastriatal implantation of genetically modified cells synthesizing nerve growth factor (NGF) constitutes one way to obtain a long-term supply of this neurotrophic factor and a neuronal protection against an excitotoxic lesion. We have investigated if NGF-loaded poly(d,l-lactide-co-glycolide) microspheres could represent an alternative to cell transplantations. These microspheres can be implanted stereotaxically and locally release the protein in a controlled and sustained way. In order to test this paradigm, the NGF release kinetics were characterized in vitro using radiolabeled NGF, immunoenzymatic assay, and PC-12 cells bioassay and then in vivo after implantation in the intact rat striatum. These microspheres were thus implanted into the rat striatum 7 days prior to infusing quinolinic acid. Control animals were either not treated or implanted with blank microspheres. The extent of the lesion and the survival of ChAT-, NADPH-d-, and DARPP-32-containing neurons were analyzed. In vitro studies showed that microspheres allowed a sustained release of bioactive NGF for at least 1 month. Microspheres implanted in the intact striatum still contained NGF after 2.5 months and they were totally degraded after 3 months. After quinolinic acid infusion, the lesion size in the group treated with NGF-releasing microspheres was reduced by 40% when compared with the control groups. A marked neuronal sparing was noted, principally concerning the cholinergic interneurons, but also neuropeptide Y/somatostatin interneurons and GABAergic striatofuge neurons. These results indicate that implantation of biodegradable NGF-releasing microspheres can be used to protect neurons from a local excitotoxic lesion and that this strategy may ultimately prove to be relevant for the treatment of various neurological diseases.
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PMID:Intracerebral implantation of NGF-releasing biodegradable microspheres protects striatum against excitotoxic damage. 1068 92

Amphetamine (AMPH) is a psychostimulant whose chronic abuse may cause impairments in attention and memory in humans. These cognitive deficits might be related to neurotoxic effects of the drug. One such toxic effect is the well-described destruction of striatal dopaminergic terminals in mammals. In the present study, we investigated the possibility that AMPH might also cause neuronal apoptosis in the rodent striatum. Administration of a dose of the drug (10 mg/kg, 4 times, every 2 h) that is toxic to dopaminergic terminals resulted in the appearance of striatal cells that were positive for cleaved caspase-3 and for terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling (TUNEL), observations that are indicative of an ongoing apoptotic process. Dual immunofluorescence staining revealed that cleaved caspase-3-positive cells express calbindin and DARPP-32, but not somatostatin, parvalbumin, or cholinergic markers. In addition, AMPH also caused increased expression of p53 and Bax at both transcript and protein levels; in contrast, Bcl-2 levels were decreased after the AMPH injections. Moreover, Bax knockout mice showed resistance to AMPH-induced apoptotic cell death but not to AMPH-induced destruction of dopaminergic terminals. When taken together, these observations indicate that injections of doses of AMPH that are known to destroy striatal dopamine terminals can also cause apoptotic death of postsynaptic medium spiny projection neurons via mitochondria-dependent mechanisms.
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PMID:Amphetamine induces apoptosis of medium spiny striatal projection neurons via the mitochondria-dependent pathway. 1573 Dec 93

Ischemia-induced striatal neurogenesis from progenitors in the adjacent subventricular zone (SVZ) in young and adult rodents has been reported. However, it has not been established whether the precursors that reside in the SVZ retain the capacity to produce the full range of striatal neurons that has been destroyed. By using a neonatal rat model of hypoxic/ischemic brain damage, we show here that virtually all of the newly produced striatal neurons are calretinin (CR)-immunoreactive (+), but not DARPP-32(+), calbindin-D-28K(+), parvalbumin(+), somatostatin(+), or choline acetyltransferase(+). Retroviral fate-mapping studies confirm that these newly born CR(+) neurons are indeed descendants of the SVZ. Our studies indicate that, although the postnatal SVZ has the capacity to produce a range of neurons, only a subset of this repertoire is manifested in the brain after injury.
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PMID:Neonatal hypoxic/ischemic brain injury induces production of calretinin-expressing interneurons in the striatum. 1872 Apr 78

Cell transplantation is a promising therapeutic approach that has the potential to replace damaged host striatal neurons and, thereby, slow down or even reverse clinical signs and symptoms during the otherwise fatal course of Huntington's disease (HD). Open-labeled clinical trials with fetal neural transplantation for HD have demonstrated long-term clinical benefits for HD patients. Here we report a postmortem analysis of an individual with HD 6 months after cell transplantation and demonstrate that cells derived from grafted fetal striatal tissue had developed into graft-derived neurons expressing dopamine-receptor related phosphoprotein (32 kDa) (DARPP-32), neuronal nuclear antigen (NeuN), calretinin and somatostatin. However, a fully mature phenotype, considered by the expression of developmental markers, is not reached by engrafted neurons and not all types of interneurons are being replaced at 6 months, which is the earliest time point human fetal tissue being implanted in a human brain became available for histological analysis. Host-derived tyrosine hydroxylase (TH) fibers had already heavily innervated the transplants and formed synaptic contacts with graft-derived DARPP-32 positive striatal neurons. In parallel, the transplants contained a considerable number of immature neuroepithelial cells (doublecortin+, Sox2+, Prox-1+, ss3-tubulin+) that exhibited a pronounced migration into the surrounding host striatal tissue and considerable mitotic activity. Graft-derived astrocytes could also be found. Interestingly, the immunological host response in the grafted area showed localized increase of immunocompetent host cells within perivascular spaces without deleterious effects on engrafted cells under continuous triple immunosuppressive medication. Thus this study provides for a better understanding of the developmental processes of grafted human fetal striatal neurons in HD and, in addition, has implications for stem cell-based transplantation approaches in the CNS.
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PMID:Histological findings on fetal striatal grafts in a Huntington's disease patient early after transplantation. 1925 52

Somatostatin (SST)-positive medium-sized aspiny interneurons are selectively spared in excitotoxicity. The biological effects of SST are mediated via five different receptors, namely somatostatin receptor (SSTR)1-5; however, SSTR subtype spared in excitotoxicity and involved in neuroprotection is not known. Dopamine- and cAMP-regulated phosphoprotein (DARPP-32) is predominantly expressed in medium-sized projection neurons that are most vulnerable in excitotoxicity. In the present study, we determined the colocalization of SST and SSTRs with DARPP-32 in rat brain cortical and striatal regions using immunofluorescence immunohistochemistry. We also determined the expression of DARPP-32 in SSTR1-5 immunoprecipitate prepared from cortex and striatum. SST-positive neurons in cortex and striatum are devoid of colocalization with DARPP-32. However, in cortical and striatal brain regions, three different neuronal populations either expressing SSTRs and DARPP-32 alone or displaying colocalization were identified. Quantitative analysis reveals that in cortex and striatum, SSTR1 and 5 are most predominant receptor subtypes colocalized with DARPP-32 followed by SSTR4, 2, and 3 in cortex whereas SSTR2, 4, and 3 in striatum. Importantly, DARPP-32 is expressed in SSTR1-5 immunoprecipitate prepared from cortex and striatum. Taken together, these results provide the first evidence that the SSTR-positive neurons lacking colocalization with DARPP-32 might be spared in excitotoxicity.
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PMID:Colocalization of somatostatin receptors with DARPP-32 in cortex and striatum of rat brain. 2211 41

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