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  • Cell & Developmental Biology  (58)
  • Glutamate synapses  (2)
  • 1
    ISSN: 1432-2072
    Keywords: GM1 ; Haloperidol ; Glutamate synapses ; Perforated PSD ; Striatum ; Dopamine receptors
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Haloperidol, a typical antipsychotic drug, causes an increase in the mean percentage of synapses within the striatum containing a discontinuous, or perforated, postsynaptic density (PSD) following 1 month of treatment (Meshul et al. 1994). This effect is not observed with the atypical antipsychotic drug, clozapine, following subchronic administration (Meshul et al. 1992a). This morphological change is also associated with an increase in the density of dopamine D2 receptors. The synapses containing the perforated PSD are asymmetrical and the nerve terminals contain the neurotransmitter, glutamate, as demonstrated by immunocytochemistry. We have also shown that subchronic treatment with haloperidol (0.5 mg/kg per day, 30 days) results in a decrease in the density of glutamate immunoreactivity within asymmetric nerve terminals associated with perforated and non-perforated PSDs (Meshul and Tan 1994). This could be due to an increase in glutamate release, perhaps due to activation of corticostriatal synapses. Agnati et al. (1983a) reported that administration of GM1 ganglioside blocks the increase in dopamine D2 receptors following haloperidol treatment. GM1 has also been shown to attenuate the release of glutamate (Nicoletti et al. 1989). In order to determine if similar treatment with ganglioside could block the haloperidol-induced ultrastructural changes noted above, rats were coadministered GM1 (10 mg/kg per day) and haloperidol (0.5 mg/kg per day) for 30 days. We report that GM1 blocked the haloperidol-induced increase in striatal asymmetric synapses containing a perforated PSD, but had no effect on the increase in dopamine D2 receptors or the decrease in nerve terminal glutamate immunoreactivity. GM1, either alone or co-administered with haloperidol, also caused a small, but significant, increase in the density of all asymmetric synapses within the striatum. It is possible that the effect of GM1 in attenuating the haloperidol-induced change in glutamate synapses with perforated PSDs is primarily postsynaptic, since GM1 did not block the change in density of glutamate immunoreactivity within asymmetric nerve terminals.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2072
    Keywords: Haloperidol ; Vacuous chewing movements ; Glutamate synapses ; Perforated postsynaptic density ; Striatum ; Tardive dyskinesia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Long-term treatment with the typical antipsychotic drug, haloperidol, can lead to a sometimes irreversible motor disorder, tardive dyskinesia (TD). It has been hypothesized that increased release of glutamate due to prolonged neuroleptic drug treatment may result in an excitotoxic lesion in specific neuronal populations within the basal ganglia, leading to TD. We reported that treatment with haloperidol for 1 month results in an increase in the mean percentage of striatal asymmetric synapses containing a perforated postsynaptic density (PSD) and that these synapses are glutamatergic. Using quantitative immunocytochemistry, we found that depending on how long the animals had been off haloperidol following subchronic (30d) treatment, there was either a decrease (1 day off) or increase (3–4 days off) in the density of glutamate immunolabeling within the presynaptic terminals of synapses with perforated PSDs. Using a rat model for TD, animals in the current study were treated for 1 year with haloperidol and spontaneous oral dyskinesias (i.e. vacuous chewing movements, VCMs) were recorded. In these long-term treated animals we wanted to determine if there was a correlation between glutamate function, as measured by changes in synapses with perforated PSDs and the density of nerve terminal glutamate immunoreactivity, and VCM behavior. In drug treated rats which demonstrated either a high or low rate of VCMs, there was a significant increase in the mean percentage of asymmetric synapses in the dorsolateral striatum with perforated PSDs in both haloperidol-treated groups compared to vehicle-treated rats. There was a small but significant increase in the density of glutamate immunolabeling within striatal nerve terminals of the high VCM group compared to the low VCM group. There was, however, no difference in the density of glutamate immunolabeling between the high VCM group compared to the vehicle-treated animals. One reason for this lack of difference was partially due to a significant increase in nerve terminal area within the high VCM group compared to either the low VCM- or vehicle-treated groups. The larger nerve terminal size in the high VCM group may be due to a small but sustained increase in glutamate neurotransmitter release with the ability of the terminal to maintain its supply of glutamate, while the terminals in the low VCM group showed evidence of glutamate depletion. This finding would be consistent with the hypothesis that increased glutamatergic activity may be associated with TD.
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  • 3
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The morphology and development of junctional complexes between blastomeres of the preimplantation rabbit embryo were investigated using several approaches. Electron microscopic examination of embryos stained en bloc with uranyl acetate, and the study of junction permeability using horseradish peroxidase and lanthanum nitrate provided information on structure, intermembrane spacing and permeability of the junctional complexes. In addition, the freeze fracture technique was used with day 5 and day 6 blastocysts, since the large size of these embryos facilitated use of this method. These experiments showed that although rudimentary junctions were present between blastomeres of the early cleavage stages, effective tight junctions were not present until the blastocyst stage. Electron microscopic examination of thin sections revealed apical foci of membrane approximation or “fusion” between trophoblast cells by day 4. Freeze fracturing revealed a lattice of interconnecting ridges (on the A face) and grooves (on the B face) in the apical region between trophoblast cells of the day 5 blastocyst. This lattice formed a continuous band along the apical margin of each cell, and therefore constituted a zonula occludens. The zonula occludens of the day 5 blastocyst averaged 2-3 ridges per lattice, while day 6 blastocysts had lattices that averaged 5-6 ridges. Also seen in the freeze fracture replicas from the day 5 and day 6 blastocysts were local accumulations of intramembranous particles on the A face. These particles were often observed in aggregates similar to those of previously described gap junctions. It could not be determined whether these small regions of particles were true gap junctions or a possible primitive form of gap junction because the complementary pitted surfaces (B face pits) were not demonstrated.
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  • 4
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 199 (1981), S. 109-127 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Protein synthesis and secretion in mouse uterine glands during the peri-implantation period were studied, by both light and electron microscopic autoradiography, after the in vivo administration of tritiated leucine (3H-leucine) and proline (3H-proline). Light microscopic autoradiography revealed that the time course of synthesis and secretion of labeled proteins was constant during days four, five, and six of pregnancy. Labeled material could be detected in the glandular lumen by 45 minutes after administration and in higher concentrations by 90 minutes after administration.Analysis of electron microscopic autoradiographs from days five and six of pregnancy showed that high levels of activity were initially present over the rough endoplasmic reticulum and Golgi complexes and subsequently declined at the longer time intervals (45 and 90 minutes), while activity over the glandular lumen increased with time. The pathway of intracellular transport to the glandular lumen appeared to be via small cytoplasmic vesicles on both days five and six of pregnancy. Additional pathways for transport of the labeled protein to the glandular lumen appeared to be present in the form of the large vesicles on day five and granules on day six of pregnancy.Throughout the peri-implantation period, mouse uterine glands were active secretory structures in which the mode of secretion was similar to other exocrine cells. Thus, the uterine glands of the mouse must be considered a source of uterine fluid proteins at the time of implantation that may contribute to quantitative changes in these proteins.
    Additional Material: 25 Ill.
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A study of the uptake of exogenous proteins, peroxidase, ferritin, and myoglobin by rabbit blastomeres of different developmental stages was undertaken to determine some of the means by which these stages ingest protein. Exposure of embryos in preimplantation stages, ranging from fertilized ovum to late blastocyst, was carried out in vitro with selected in vivo controls. Blastomeres of early cleavage stages up to the morula show little uptake of peroxidase. However, the endocytosis of peroxidase greatly increases with the morula stages and continues at an elevated level through the blastocyst stages. The uptake of the tracer is initially accomplished via micropinocytotic vesicles and tubules and can have several subsequent fates. The tracer can pass into larger vacuoles and be transported into the cavity of the blastocyst, or can pass into multivesicular bodies where it is presumably degraded by the lysosomal system for cellular use. The use of myoglobin at selected blastocyst stages yielded results similar to those obtained with peroxidase. However, the response by the blastomeres to ferritin is different. Endocytosis of ferritin is scant at all preimplantation stages, even though the ferritin has no difficulty reaching the surface of the blastomeres. The experiment with mechanically denuded blastocysts indicated that ferritin did not adsorb to the cell surface.
    Additional Material: 1 Tab.
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  • 6
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: A glycoprotein coat is demonstrable on the free surface of both the blastocyst and uterine luminal epithelium of the mouse on day 4 and day 5 of normal pregnancy, and on day 7 of delayed implantation, using concanavalin A-peroxidase and ruthenium red. The coats are apparently negatively charged, as shown by their binding with colloidal thorium dioxide. The cell coat on uterine epithelium is appreciably thicker than that on the blastocyst. The information currently available is sufficient to suggest that simplistic mechanisms such as change in charge or total thickness cannot be the sole basis of initial adhesion, but that some localized reduction of the uterine surface coat accompanies adhesion. However, considerably more information is necessary concerning the nature of the surface coats before a more comprehensive understanding of the role of adhesion in implantation can be achieved.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The surface coat of syncytial trophoblast from term human placentas was studied using cytochemical methods (colloidal iron, alcian bluelanthanum nitrate, dialyzed iron) in coordination with tissue enzyme digestions (trypsin, neuraminidase) and sialic acid analyses. The presence of at least two highly acidic anionic components that contribute significantly to the surface negativity of trophoblast has been demonstrated. The first of these, sialic acid, was removed with neuraminidase. Tissue digestion with this glycosidase was accompanied by a decrease in trophoblast surface staining with colloidal iron, a decrease in tissue sialic acid, and an increase in the concentration of sialic acid in the incubating medium. Results from methylation experiments were consistent with the presence of sialic acid. The second anionic component(s) was identified by removal with trypsin of a glycocalyx constituent that stained with both colloidal iron and lanthanum. After trypsinization, tissue sialic acid levels were not significantly different from control values, and no detectable sialic acid was present in the incubating medium. The identity of this anionic component has not been established. Both sialic acid and nonsialic acid acidic components are distributed in higher density on membrane of microvilli than on intermicrovillous surface membrane. In addition, the sialic acid moieties appear to be clustered in the glycocalyx.
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  • 8
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 225 (1989), S. 329-340 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: The structure of trophoblast of the baboon blastocyst undergoes a number of maturational changes from the early blastocyst to the late blastocyst stage. The striking expansion of the blastocyst that occurs during the preimplan tation period is accompanied by the development of an extensive endocytic apparatus. Cationized ferritin labels coated depressions and vesicles near the apical cell surface, numerous uncoated tubules and larger apical vesicles, and multivesicular bodies within trophoblast cells. Basally and laterally the labeled components are primarily small uncoated vesicles and tubules. Small, discrete clusters of ferritin particles were seen within the basolateral compartment between trophoblast and its basal lamina and beneath trophoblast cells that do not have a basal lamina. The results indicate that ingested materials may be directed in two pathways, one involving breakdown within the lysosomal system and one involving transcytosis. The zona pellucida is a trilaminar structure consisting of a fibrillar outer layer that often contains spermatozoa, an intermediate zone, and an inner layer containing columns of dense zonal material. Loss of the zona occurs after expansion of the blastocyst and development of the endocytic organelles. During the late blastocyst stage, syncytial trophoblast differentiates at the margin of the polar trophoblast. Because blastocysts were flushed from the uterus, it could not be determined whether azonal blastocysts had been adherent to the uterine surface prior to collection.
    Additional Material: 16 Ill.
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  • 9
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 226 (1990), S. 237-248 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: During the blastocyst stage of development in the baboon, the inner cell mass changes from an irregular accumulation of cells within the cavity of the blastocyst to a disk at one side of the blastocyst and finally to a spherial mass of epiblast cells exhibiting a distinct polarity. The cells that will become the primitive endoderm are first seen as flattened but undifferentiated cells on the cavity side of the disk-shaped inner cell mass. After endoderm cells develop their typical cytological characteristics, they extend well beyond the inner cell mass to form parietal endoderm. A basal lamina develops associated with the epiblast cells and mural trophoblast, but not with either parietal or visceral endoderm. Cytological differentiation of inner cell mass cells includes increased numbers of polyribosomes and a change in mitochondria from long, convoluted structures to short, more typical shapes. Evidence that epiblast is polarized is seen by the late zonal blastocyst stage. Apical junctional complexes develop within the center of the epiblast. These junctions presage the development of the potential amniotic cavity. Large vacuoles containing cell debris, some of which contain nuclear fragments, are present at all stages. Extensive cell death occurs during growth of the blastocyst, but the pattern appears to be random and products of cell death are readily phagocytized by adjacent cells.
    Additional Material: 10 Ill.
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  • 10
    Electronic Resource
    Electronic Resource
    New York, NY [u.a.] : Wiley-Blackwell
    The @Anatomical Record 167 (1970), S. 231-251 
    ISSN: 0003-276X
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Medicine
    Notes: Cytological investigation of Hofbauer cells in various stages of gestation reveals that they are similar to normal macrophages except for unusually large cytoplasmic flanges and included vacuoles. The system of vacuoles is apparently the result of macropinocytotic activity. The individual vacuoles undergo asymmetrical collapse in regions adjacent to small juxtavacuolar tubules thought to be derived from the agranular endoplasmic reticulum. In addition, coated micropinocytotic vesicles are common. Hofbauer cells thus appear to be a type of macrophage with an unusual capacity for fluid ingestion. In younger placentas, Hofbauer cells are usually associated with extracellular compartments within the stroma. These compartments are relatively free of collagen fibrils and demonstrable ground substance and are clearly demarcated from the rest of the stroma by processes of fibroblasts. The abundance of these cells in early placentas, their location in the stroma, and evidence of their pinocytotic activity suggest that these cells may play a role in removal of proteins from interstitial fluid. Hofbauer-like cells were also studied in the guinea pig and the little brown bat. Of these two species, the Hofbauer-like cells of the bat more closely resemble human Hofbauer cells in that they show evidence of extensive macropinocytotic activity.
    Type of Medium: Electronic Resource
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