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J R Connor

Publications and source records attributed to J R Connor.

At least 145 records · Page 8Linked to original sources
PubMed1987

Development of transferrin-positive oligodendrocytes in the rat central nervous system.

Transferrin is the second most abundant plasma protein and functions to transport iron. It is an essential constituent in culture media for virtually all cells. In a recent study, we reported that transferrin (Tf) is specifically located in oligodendrocytes in the rat nervous system. This investigation examines immunohistochemically the development of Tf in the cerebral cortex, corpus striatum, and spinal cord. Tf is first seen in oligodendrocytes in the spinal cord white matter at 5 days of age. The immunoreactivity is confined to the white matter in the periphery of the spinal cord between 5 and 8 days of age. By 10-12 days of age, the number of immunoreactive oligodendrocytes in the spinal cord white matter increases considerably, corresponding to the onset of myelination. Tf-positive oligodendrocytes are first found in the gray matter at 15 days of age. By 30 days of age, the number and distribution of Tf-positive oligodendrocytes in both the brain and spinal cord have reached the adult pattern. The results of this study demonstrate a spatial and temporal association between Tf development and myelinogenesis. This suggests that part of the process of differentiation of oligodendrocytes includes the accumulation of Tf, perhaps in order to support the metabolic demands associated with the production and maintenance of myelin.

Animals↗
PubMed1987

Glial fibrillary acidic protein immunohistochemistry of spinal cord astrocytes after induction of ischemia or anoxia in culture.

The effects of ischemia (removal of oxygen and glucose for 4 h) and anoxia (removal of oxygen alone) on astrocytes were studied in dissociated cultures of E14 spinal cord containing both neurons and astrocytes. In addition, a group of cultures was treated with a low Na+, low Ca2+, and high K+ medium during the 4-h ischemic period (ischemia-protected group), a process that protects neurons from ischemic damage under identical conditions. Astrocytes were examined immunohistochemically using glial fibrillary acidic protein (GFAI) antiserum 24 h after insult. Densitometry and statistical analysis (1-way analysis of variance [ANOVA], a priori; 2-tailed Tukey-t, a posteriori) of the digitized images of the somata and processes of astrocytes in the anti-GFAP reacted cultures showed significant differences between the groups; a significant increase (P less than 0.01) in the GFAP-positive reaction in the somata of ischemic astrocytes and a significant decrease (P less than 0.01) in the GFAP-positive reaction in the processes of ischemic, ischemia-protected, and anoxic astrocytes. There were no significant differences in the GFAP immunoreactivity of somata between control, ischemia-protected, and anoxic astrocytes or of processes from ischemic, ischemia-protected, and anoxic astrocytes. These data show that following ischemia cultured astrocytes increase somatic GFAP immunoreactivity compared to all other groups tested whereas the staining intensity for GFAP was decreased in the processes of all three experimental groups compared to controls. Ischemia protection resulted in the absence of the enhancement of somatic GFAP immunoreactivity. The relationship of the astrocytic response and the type of cellular stress is discussed.

Animals↗
PubMed1987

Receptor-mediated transcytosis of transferrin across the blood-brain barrier.

The perfusion of rat brain with 125I-transferrin resulted in a receptor-mediated uptake of transferrin into the endothelium of the blood-brain barrier followed by its detection in the brain. During a pulse-chase experiment, 125I-transferrin accumulated in the endothelial cells during the pulse, with a decrease of this intraendothelial radioactivity during the chase associated with a concomitant increase in the nonvascular elements of the brain. The receptor-mediated movement of transferrin across the blood-brain barrier suggests that the brain may derive its iron through the transcytosis of iron-loaded transferrin across the brain microvasculature. We discuss the likelihood that aluminum and other potentially toxic heavy metals, which also bind tightly to transferrin, may enter the brain by this pathway. We also discuss the possibility that other large molecules including neuroactive peptides and neurotrophic viruses may enter the brain through a similar receptor-mediated, vesicular transcytotic route.

Animals↗
PubMed1987

Regional variation in the levels of transferrin in the CNS of normal and myelin-deficient rats.

Transferrin (Tf), the iron mobilization protein, is synthesized mainly in the liver. Recently, both Tf and a mRNA for Tf have been demonstrated in oligodendrocytes in the rat brain. The present study used a biochemical assay for determining the levels of Tf in various brain regions of normal rats compared with the level of those obtained from rats with a genetic mutation characterized by an almost complete failure to develop myelin. In myelin-deficient (md) rats, no Tf-positive oligodendrocytes were seen immunohistochemically in the gray or white matter of the CNS. Quantitatively, levels of Tf throughout the CNS of the md rat were decreased to approximately 5% of the normal values despite a normal hepatic synthetic rate. In the normal rat brain, the cerebellum contained the highest concentration of Tf, followed by the pons, the cerebral cortex, and the caudate-putamen, with the latter two sites being similar. Regional variation in the amount of Tf was in general agreement with published reports on the variation of iron and Tf receptor levels in the CNS. Immunohistochemical examination with antiserum to galactocerebroside (a myelin-specific lipid) was used for extending biochemical reports that glycolipid-synthesizing enzymes are deficient in md rats. No immunostaining in the md rat was observed following immunoreaction for galactocerebroside, whereas white matter oligodendrocytes were intensely marked in the normal rat. Robust astrogliosis was present in both the gray and white matter of the md rats. It is not known at present whether the ability to accumulate Tf is necessary for oligodendrocytic survival or if Tf accumulation is more directly related to myelinogenesis.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1986

Somatostatin-like neurons are expressed in fetal neocortical homografts in adult rat spinal cord.

Fetal central nervous system homografts to adult spinal cord are considered a potential aid for recovery of function after paraplegia. This study utilizes somatostatin (SOM) immunohistochemistry to study the organization of an embryonic day 14 (E14) neocortical homograft into the spinal cord of an adult host over 6 postoperative months. Although the E14 homograft does not contain SOM-positive cells, SOM-reactive neurons are expressed by 30 days postimplantation and are still present in 6-month-old homografts. SOM-immunoreactive neurons are bitufted or multipolar and have dendrites that are confined to the graft. The homograft contains SOM-immunoreactive axons entering and/or exiting from lamina II in the host dorsal horn and SOM-positive homografted neurons send axons into the host ventral columns. These data show that the SOM peptide neocortical phenotype is preserved in homografts to spinal cord but there is anatomical host-homograft integration.

Animals↗
PubMed1986

The distribution of transferrin immunoreactivity in the rat central nervous system.

Recent studies have demonstrated receptors in the nervous system for transferrin, the iron binding and transport protein in the blood. This study using immunohistochemistry at the light and electron microscopic levels demonstrates that transferrin (Tf) is found predominantly in oligodendrocytes in both the gray and white matter of the cerebral cortex, cerebellum and spinal cord. Within the cerebral cortex, layer V has more Tf-labeled cells than the other cortical layers. In the spinal cord, lamina VII has the highest density of Tf-positive cells. Based on location, 3 types of oligodendrocytes can be described: perineuronal, interfascicular and perivascular. In addition to oligodendrocytes, endothelial cells and possibly some neuronal membranes of layer V pyramidal and anterior horn cells label with Tf antiserum. Ultrastructurally, Tf reaction product is homogeneously distributed throughout the perinuclear cytoplasm of both oligodendrocytes and endothelial cells. The importance of iron in motor and behavior function is well established although the mechanism of action of iron in the CNS is not well understood. The presence of Tf in oligodendrocytes implies that these neuroglia are involved in iron mobilization and storage in the CNS. Stored quantities of iron and the ability to mobilize the iron through stored transferrin may be the reason for the extreme dietary restrictions necessary to induce iron-deficient CNS disorders.

Animals↗
PubMed1986

Vasoactive intestinal polypeptide neurons in fetal cortical homografts to adult rat spinal cord.

Transplants of central nervous system to adult spinal cords are considered as potential aids in regeneration of the spinal cord and/or recovery of function after injury. The organization and development of the implant are important issues in seeking the potential for a transplant and host to become functionally integrated. This study uses embryonic cerebral cortex transplanted into the spinal cord of adult rats (T6) and examined the development and organization of the transplant with an antibody to vasoactive intestinal polypeptide (VIP). The cell bodies of VIP neurons are in the implants at 30 days postimplantation, but few of the somata have processes. By 45 days postimplantation, VIP neurons in the implant have dendrites and axons and are clearly recognizable as cortical bipolar cells which are not normally present in the thoracic spinal cord. These data show that neurons in embryonic cerebral cortical implants into the spinal cord elaborate the appropriate biochemical and morphological constituents in spite of the ectopic location. However, the cell processes develop at a slower than normal pace. Morphological interaction between the host spinal cord and the implant can be demonstrated possibly as early as 45 days postimplantation and clearly at 6 months following the implant. Thus, further examination of cerebral cortical implants as a potential aid in alleviation of paraplegia subsequent to spinal cord injury is warranted.

Animals↗
PubMed1985

Lyso(bis)phosphatidic acid: a novel source of arachidonic acid for oxidative metabolism by rabbit alveolar macrophages.

To identify the source of arachidonic acid utilized for eicosanoid production, rabbit alveolar macrophages were challenged with 1.0 microM 12-O-tetradecanoylphorbol-13-acetate (TPA) or 3.8 microM Ca+2 ionophore A23187 for 3 h. Upon stimulation with TPA, a loss of [3H]arachidonic acid from phosphatidylcholine, phosphatidylethanolamine, lyso(bis)phosphatidic acid, and phosphatidylserine/phosphatidylinositol was observed. Although calcium ionophore stimulated the liberation of arachidonate solely from phosphatidyl-ethanolamine and phosphatidylcholine, it proved to be a poor stimulus for macrophage-synthesis of eicosanoids. Our evidence suggests that degradation of phosphatidylinositol and lyso(bis)phosphatidic acid induced by TPA yields a source of arachidonate which is the preferred substrate for oxidative metabolism by the cyclooxygenase and lipoxygenase pathways.

Animals↗
PubMed1985

A demonstration of glial filament distribution in astrocytes isolated from rat cerebral cortex.

Astrocytes have been classically described based on morphological characteristics as either protoplasmic or fibrous. However, the appearance of astrocytes at the light microscopic level following immunoreaction with glial filament acidic protein antisera or Cajal's gold-chloride method is markedly different from the morphology of Golgi-impregnated or horseradish peroxidase-filled astrocytes. The present study combines immunohistochemistry using glial fibrillary acidic protein antisera and a cellular suspension of structurally intact astrocytes isolated from the rat cerebral cortex to demonstrate that the distribution of glial filaments is limited to major astrocytic processes. Because the sheet-like processes which decorate the major branches of protoplasmic astrocytes do not contain glial filaments, the entire protoplasmic astrocyte is not visible when viewed in situ in the gray matter of the cerebral cortex. Thus staining techniques that have a propensity for the glial filaments such as antisera to glial fibrillary acidic protein and the gold-chloride method provide only a skeletal outline of the major processes of the protoplasmic astrocyte. On the other hand, fibrous astrocytes which do not have feathery decorations on major processes are visible in the cerebral cortex in their structural entirety. The present investigation also offers additional evidence of the specificity of glial fibrillary acidic protein antisera for astrocytes.

Animals↗
PubMed1985

Comparison of herpes simplex virus type 1 DNA replication and virus production in murine bone marrow-derived and resident peritoneal macrophages.

The mechanism of resistance of murine macrophages (M phi) to infection by herpes simplex virus type 1 (HSV-1) was examined. Infection of bone marrow-derived M phi (BMDM phi) and resident peritoneal M phi (Res-M phi) was compared with infection of permissive Vero cells. In contrast to HSV-1 infection in Vero cells, no infectious virus was produced from either M phi cell type. However, marked cytopathic effect (c.p.e.) was evident in BMDM phi at 48 h post-infection, while there was no c.p.e. at any time post-infection in the Res-M phi. Cloned EcoRI subgenomic fragments representing the entire HSV-1 genome were used as probes in DNA :DNA hybridization experiments to determine the viral genome content in the infected cell types. In Res-M phi, HSV-1 DNA was present at early times post-infection but declined rapidly. In BMDM phi, the virus genome was always detected and increased with time after infection. The results suggest that Res-M phi restrict HSV-1 production at a point prior to viral DNA synthesis, whereas the block in HSV production in BMDM phi occurs at a later stage in the viral replicative cycle.

Animals↗
PubMed1984

Vasoactive intestinal polypeptide-immunoreactive neurons in rat visual cortex.

An antibody to vasoactive intestinal polypeptide (VIP) was used to examine the forms of VIP-positive neurons and the synapses made by VIP-positive axon terminals. Vasoactive intestinal polypeptide-positive cells are most common in layers II and III and the majority of them are typical bipolar neurons, with two primary dendrites which emanate from the upper and lower poles of the cell body. Their somata, which have only a few symmetric and asymmetric synapses, generally have a fusiform or "tear-drop" shape and contain nuclei with a vertically oriented cleft. The dendritic trees are arranged vertically and often extend through five cortical layers. The axons are thin and extend either from the soma or from one of the primary dendrites. The axons also follow a vertical trajectory. Other VIP-positive neurons are modified bipolar cells and a few of them are multipolar cells. The synapses formed by the VIP-positive axon terminals in the neuropil are symmetric in form, and although the synaptic clefts are narrow, the junctions are usually long and continuous, rather like those described for asymmetric synapses. Most of the VIP-positive axon terminals synpase with small dendritic shafts, but a few synapse with neuronal cell bodies. Since the majority of the VIP-positive neurons are bipolar cells it is concluded that these are the source of most of the VIP-positive axon terminals. If this is so, then the VIP-positive bipolar cells form symmetric synapses. This is in contrast to the observations of Peters and Kimerer (1981. J. Neurocytol. 10, 921-946) for the bipolar cells they examined in a Golgi-electron microscopic study had axon terminals forming asymmetric synapses. It is suggested that this disparity can be reconciled if it is assumed that the bipolar cell population consists of subgroups which have different biochemical characteristics and different synaptic relationships.

Animals↗
PubMed1983

Biochemical characteristics of dissociatively isolated aortic proteoglycans and their binding capacity to hyaluronic acid.

Proteoglycans were extracted from pigeon aortas with 4.0 M guanidine hydrochloride containing protease inhibitors to characterize the proteoglycan (PG) types, to examine and define their association with hyaluronic acid, and to compare pigeon aortic PG with human aortic PG isolated and characterized under similar conditions. Following chromatography of guanidine hydrochloride extracts on Sepharose CL-4B under dissociative conditions, two populations of PG were isolated. PG I, eluting at the column void volume, contained predominantly (83.2%) chondroitin sulfate whereas PG II, eluting at a Kav of 0.40, contained predominantly dermatan sulfate (54.7%). Following centrifugation, 76 and 63% of PG I and PG II, respectively, were located in the bottom two-fifths (p greater than 1.43 g/ml) of a CsCl gradient. Only PG I, predominantly chondroitin sulfate, was effective in associating with hyaluronic acid to form high molecular weight aggregates. The specific association was illustrated by removing endogenous arterial hyaluronic acid remaining in the preparation and demonstrating increasing formation of aggregate with increasing addition of human umbilical cord high molecular weight hyaluronic acid. The results of the study illustrate that artery PG of the pigeon are similar in distribution to those described for the human aorta and contain at least three types of PG, a chondroitin sulfate PG, a dermatan sulfate PG, and a polydisperse heparan sulfate PG. The chondroitin sulfate PG but not the dermatan sulfate PG are capable of forming high molecular weight aggregates with hyaluronic acid.

Animals↗
PubMed1982

A quantitative Golgi study in the occipital cortex of the pyramidal dendritic topology of old adult rats from social or isolated environments.

It has been previously established that the housing condition influences the appearance of the dendritic tree in young animals. The purpose of this investigation was to determine the extent of the influence that the housing condition exerts on morphometric studies involving old animals. Specifically, we found superficial pyramidal cells from the visual cortex of socially aged 20-month-old rats had more extensive oblique dendritic trees than neurons from isolated rats of the same age. The basal dendritic tree of neurons from socially reared rats was denser nearest layer IV while the basal dendritic tree of neurons from isolated rats appeared to shift away from layer IV. Our results indicate that the external environment is an independent variable and cortical dendritic morphology is a dependent variable in studies on old adult rats. Thus, the external environment should be considered in reporting results of aging studies on dendritic topology.

Aging↗
PubMed1982

A comparison of dendritic spine number and type on pyramidal neurons of the visual cortex of old adult rats from social or isolated environments.

The present study determined the effect of the housing condition experienced by old adult male rats on the appearance and number of dendritic spines. Specifically, 20-month-old rats were killed following 6 months of living in either a social environment (three to a cage) or living alone. The total number of dendritic spines per unit length was examined along segments of oblique, basal, and apical dendritic branches of pyramidal cells from layers II, III, Va, and Vb of the visual cortex. In addition to determining the total spine number, the spines were differentiated into two topographical categories: those with a lollipop configuration (type L) and those with a nubbin configuration (type N). Our results show that neither the total spine density nor the type L spine density were generally influenced by the two housing conditions. However, the density of type N spines was almost always greater on neurons from rats which had been living alone irrespective of the cortical layer or the dendritic segment counted. Some differences in total spine density and type L spine density were noted when neurons from the same environment but different cortical layers were compared, and these findings are discussed. However, the major focus of this paper was to extend our previous report of a selective increase in type N spines with age. We now show that in addition to increasing with age, type N spine density is also selectively increased by the condition of social deprivation.

Animals↗
PubMed1982

High molecular weight proteoglycans biosynthesized in culture by pigeon aortas.

The properties of aortic proteoglycans synthesized in vitro were examined to demonstrate synthesis of intact proteoglycans by aortic tissue in culture and to compare labeling and synthetic rates of two different populations of proteoglycan. Following 3, 6, or 9 h of incubation in medium containing [35S]sodium sulfate and [3H]serine, the tissue was extracted with 4.0 M guanidine hydrochloride containing protease inhibitors. Extracts were chromatographed on Sepharose CL-4B and subjected to buoyant density centrifugation under dissociative conditions. Radioactive precursors were incorporated into two major populations of aortic proteoglycan, one of high molecular weight eluting near the void volume of Sepharose CL-4B (Proteoglycan I) and one of lower molecular weight (Proteoglycan II) having a Kav of 0.40-0.44. The radioactively labeled proteoglycans were localized at densities 1.50-1.56 g/ml (Preparation 1) and 1.43-1.49 g/ml (Preparation 2) following CsCl buoyant density centrifugation. Both proteoglycan populations had increased incorporation of 35S and 3H over time. At all times the lower molecular weight proteoglycan had a higher specific activity (dpm 35S and 3H/micrograms hexuronic acid). At 3, 6, and 9 h, the specific activity of Proteoglycan II was 8.2-, 6.7- and 3.0-fold higher than Proteoglycan I using 35S and 13.0-, 8.1- and 2.7-fold higher using 3H, suggesting different synthetic rates for the two proteoglycans. The results illustrate synthesis of intact proteoglycans during short-term artery culture. The proteoglycan types have size and buoyant density characteristics as described for artery, but based upon changes in specific activity ratios, the two proteoglycan populations differ in rates of synthesis.

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