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PubMed1975

Scanning electron microscopy of a second type of supraependymal cell in the monkey third ventricle.

The third ventricle of monkeys has been examined with the scanning electron microscope (SEM). Two populations of supraependymal (SE) cells were distinguished on the basis of morphology and location. One type has been previously reported (Coates, '72, '73a,b,c). Another, type 2 SE cell, is now described. Type 2 SE cells were found in the third ventricle of both sexes and in all age groups although the numbers varied highly from animal to animal. The most common site for type 2 SE cells was the floor and transition zone of the third ventricle. Visualized with SEM, these cells had variable morphology, but may be characterized by a small cell body, few non-branching processes some of which were flared and surface features such as ruffled membranes. Type 2 SE cells most likely correspond to Kolmer or epiplexus cells originally described in association with the choroid plexus. As such, they are probably phagocytes.

Animals↗
PubMed1984

From bone lining cell to osteocyte--an SEM study.

We describe the SEM appearance of the rat endosteal bone lining cell ( BLC ) population, and the sequence of morphological changes of these cells as they self-incorporate into unmineralized bone matrix (osteoid), establish intercellular connections, and construct lacunae. The osteoblast/nascent osteocyte series was progressively unsheathed by gentle digestion of the osteoid with 0.25% collagenase. The osteoblasts which leave the polygonally packed BLC compartment rapidly develop numerous complexly branched processes that contact the processes elaborated by previous generations of maturing and mature osteocytes. As osteoblasts mature and approach the mineralization front, they appear to lose processes. The mature cells begin to form osteocyte lacunae by depositing an asymmetric perimeter of woven collagen fibrils, such that as the cells roof-over, the lacunae appear as pocketlike constructions. The collagen fibrils on the perilacunar matrix are oriented in a tangential or circular pattern, while those in the more distal matrix are arranged in a parallel pattern. With the completion of a lacuna, its wall appears to mineralize quickly, for lacunae could be recognized only when they are forming.

Animals↗
PubMed1982

A Golgi and ultrastructural study of the monkey globus pallidus.

Golgi preparations reveal that the most frequent type of pallidal neuron (principal cell), which has been recognized in all previous reports, is large (20-50 microns), fusiform, with dendrites up to 700 microns long. Large neurons of globular shape are less frequently impregnated. The morphology of dendrites varies considerably within the same neuron. Some exhibit numerous spines and protrusions and are seen to terminate in elaborate arborizations. A small interneuron (12 microns), with relatively short dendrites, up to 150 microns, and a short sparsely branching axon is observed less frequently. At least two types of afferent axons are present. A small-diameter fiber from the neostriatum enters the pallidum in bundles and gives rise to numerous thin branching processes with varicosities about 1 micron in size. The axon collaterals are oriented orthogonal to the main axon and parallel to the dendrites of principal cells. A large-caliber fiber with clusters of 2-3 microns swellings can also be seen in close proximity to large pallidal dendrites. Ultrastructurally, principal cell dendrites (trunks, spines, and protrusions) are totally covered by synapsing axon terminals. In contrast, some small dentrites, presumed to belong to interneurons, form very few synapses. At least six categories of profiles containing vesicles are observed. One group has cytologic features of dendrites and participates in serial and triadic synapses with other profiles in the pallidal neuropil. Results suggest that the synaptic organization of the globus pallidus may be viewed as a repetitive, geometric arrangement of striatal and other afferent axons ensheathing and synapsing with the dendrites of principal cells. This pattern is interrupted by the presence of presynaptic dendrites, probably belonging to interneurons, which participate in complex synaptic arrangements.

Afferent Pathways↗
PubMed1986

Immunocytochemical localization of luteinizing hormone-releasing hormone (LHRH) pathways in the sheep brain during anestrus and the mid-luteal phase of the estrous cycle.

The luteinizing hormone-releasing hormone (LHRH) system of the sheep brain was examined by light microscopic immunocytochemistry with thick, unembedded sections. We compared the distribution and morphology of LHRH cells and their fibers in intact and ovariectomized anestrous ewes, and in breeding season ewes during the mid-luteal phase of their estrous cycle. In all animals, a majority of LHRH neurons were found in the medial preoptic area adjacent to the organum vasculosum of the lamina terminalis. These cells formed a continuum rostrally with immunoreactive neurons in the diagonal band of Broca and medial septum and caudally with cells in the ventrolateral anterior hypothalamus and lateral hypothalamus. Relatively few cells (1-2%) were seen in the arcuate nucleus or its vicinity. Preoptic LHRH neurons project to the tubero-infundibular sulcus of the median eminence by at least two routes: a major ventrolateral projection above the optic tract in the anterior and lateral hypothalamus, and a less prominent periventricular pathway along the third ventricle. LHRH fibers were also observed in a number of extrahypothalamic regions, including the medial amygdala and the accessory olfactory bulb. Immunoreactive LHRH neurons in the sheep exhibited a complex light microscopic morphology unlike that seen in LHRH cells of any other species to date. LHRH cells with extensive, branching processes were frequently found in clusters with close somatic appositions between neighboring cells. Multiple thin protuberances emanated from the soma of many immunoreactive neurons. Immunoreactive fibers with beaded varicosities often were intimately associated with both cell bodies and their dendritic processes. Morphometric analyses revealed that preoptic LHRH neurons in three of four mid-luteal phase ewes had a shorter total dendritic length than those neurons in either intact or ovariectomized anestrous ewes, but this difference between breeding season and anestrous ewes was not statistically significant. Evidence for possible seasonal and/or steroid-induced alterations in the morphology of LHRH neurons must be documented by further studies, including immunocytochemical observations at an ultrastructural level.

Animals↗
PubMed1988

Anatomy of the adrenergic system in the medulla oblongata of the tree shrew: PNMT immunoreactive structures within the nucleus tractus solitarii.

The adrenergic system in the medulla oblongata of tree shrews was investigated by immunocytochemistry with an antibody against phenylethanolamine-N-methyltransferase. Two groups of adrenergic cells, which are equivalent to those of other species, were detected: Group C1 in the ventrolateral medulla and group C2 in the dorsomedial medulla. Adrenergic cells in C1 are located around the lateral reticular nucleus or between its subdivisions. They are mostly multipolar with branched processes. In group C2, some immunoreactive cell bodies smaller than those in C1 and many nerve terminals are found in the motor nucleus of the vagus, but most of the adrenergic cells and fibers are observed in the nucleus tractus solitarii. The cytoarchitecture of this nucleus resembles that described before for the rhesus monkey. In contrast to the rat, the subnucleus gelatinosus, which according to other authors receives cardiac and gastric afferents, is a prominent structure in immunocytochemically as well as conventionally stained sections. Adrenergic cell bodies and their fibers form a ring around this nucleus, but no immunoreactive structures are found within it. In the dorsomedial part of the nucleus tractus solitarii, adrenergic neurons are accumulated. They are often located in close proximity to blood vessels. Elongated immunoreactive neurons in the medial subdivision of the nucleus also seem to project in the direction of the dorsal area. Our data give new information about the adrenergic system in the medulla oblongata, especially in the nucleus tractus solitarii of the tree shrew, a species that provides a useful model of a small primate brain.

Animals↗
PubMed1990

Structure of the olfactory bulb of the hedgehog (Erinaceus europaeus): a Golgi study of the intrinsic organization of the superficial layers.

The intrinsic organization of the mitral cell, external plexiform, and glomerular layers of the main olfactory bulb of the insectivore hedgehog were studied with the Golgi method. This study completes our previous description of the cell types in the granule cell layer in the same subject (López-Mascaraque et al., J. Comp. Neurol. 253:135-152, '86). In the present contribution the morphology of mitral, internal, and middle tufted cells is described with particular interest in the formation and arrangement of glomerular tufts by the primary dendrites, and the disposition of the secondary dendrites. Three types of intrinsic cells were found in the external plexiform layer: Van Gehuchten cells, satellite cells, and horizontal cells. All these cells display unusual patterns of branching processes that were difficult to classify as dendritic or axonal. The close relationship between some processes of the satellite cells with the mitral or tufted cell dendrites is noted, suggesting that these cells may be inhibitory in nature. The external tufted cells are described, and several aspects pertaining to their morphology were considered in order to distinguish them from periglomerular cells and from the remaining tufted cells. External tufted and periglomerular cells appear to be intrinsic neurons, having axons distributed in the periglomerular region, most probably devoted to relating different olfactory glomeruli. The arrangement of glomeruli in the glomerular layer and distinctive characteristics with respect to other mammals were considered from a comparative point of view.

Animals↗
PubMed1995

Acutely isolated and cultured cells from the electrosensory lateral line lobe of a gymnotiform teleost.

The present study established the morphological and immunocytochemical criteria necessary to identify neuronal and nonneuronal cells after dissociating select regions of the medullary electrosensory lateral line lobe of adult weakly electric fish (Apteronotus leptorhynchus). Cells dissociated from the pyramidal cell body layers of the centromedial and lateral segments exhibited similar characteristics in the acutely dissociated preparation and up to 14 days in culture. Basilar and nonbasilar pyramidal cells were tentatively identified according to a bipolar or monopolar process extension, and polymorphic cells by the extension of three or more processes and positive immunoreactivity for gamma-aminobutyric acid. Nonneuronal cells were identified by the pattern of process arborization and positive immunolabel for gamma-aminobutyric acid or glial fibrillary acidic protein. Neuronal cells increased in total number over the first 4 days and could appear for the first time on any day in culture. Individual pyramidal cells could maintain their morphology from the time of dissociation and over several days in culture. Pyramidal cell processes were phenotypically similar to apical and basal dendrites found in situ but were reduced in size and in the degree of process branching. These results indicate that dissociated adult apteronotid neurons can maintain a morphology sufficiently similar to that found in situ as to allow tentative identification, opening up a wide range of possibilities for studying the electrophysiological and regenerative properties of electrosensory neurons.

Animals↗
PubMed1994

In vivo staining of oligodendroglia in the rabbit retina.

We have discovered that a strongly fluorescent dye, sulforhodamine 101, when injected intravitreally in vivo, very effectively stains a class of star-shaped cells in the innermost layers of the rabbit retina. The cells were strictly confined to the region containing medullated fibers and emitted dichotomously branching processes that ended up running some distance along the myelinated fibers. In favorable cases they could be seen to ensheath the fibers in a tube-like fashion. No other retinal cells were stained. Shortly (hours) after the injection, the stain appeared in the cell cytoplasm, but it later became progressively more localized to intracellular granules. Most of the dye had disappeared after 2 days. Oligodendrocytes and astrocytes are the only cells known to be confined to the region of the medullated fibers in the rabbit retina, and hence the sulforhodamine 101-stained cells should be one of these two types. Sulforhodamine 101-stained cells were indistinguishable from oligodendrocytes identified by 2',3'-cyclic nucleotide phosphodiesterase (CNP) immunohistochemistry, and sequential staining showed them to be the same. Sulforhodamine 101-stained cells were microinjected with lucifer yellow after lightly fixing rabbit retinas with formaldehyde and were found to be indistinguishable from oligodendrocytes. Glial fibrillary acidic protein staining for astrocytes showed fiber bundles that to some extent were similar to the bundles stained by sulforhodamine 101, but at the level of individual fibers, it was impossible to establish any concordance. Sulforhodamine 101 thus appears to stain oligodendrocytes rather than astrocytes in the rabbit retina. A related dye, rhodamine 123, also stained rabbit oligodendrocytes, but with poor contrast because many other cells and structures were also stained.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Epidermal growth factor responsiveness of a new human neuroblastoma cell line.

A human neuroblastoma cell line, CA-2E, has been established from a bone-marrow aspirate of a 16-month-old boy with progressive disease. The karyotype and antigen phenotype of the cells correspond to those of a neuroblastoma. This cell line grows well in liquid cultures supplemented with 5% fetal calf serum; conversely, colony formation in semi-solid medium by cells from early passages is dependent upon exogenous EGF. With time in continuous culture, the cloning efficiency in the absence of EGF increases, but the line remains sensitive to EGF, as evidenced by an enhancement of the number and size of colonies. A relative dependence upon EGF in liquid cultures has also been clearly demonstrated by limiting the concentration of serum. Long-term (over 2 weeks) treatment with EGF results in a decreased rate of proliferation, a decreased proportion of clonogenic cells, and the appearance of flat, epithelial-type cells. In some experiments, EGF also has a remarkable effect in inducing neurite outgrowth and process branching. Our results suggest that EGF may have both proliferation- and differentiation-inducing effects on this neuroblastoma cell line. We have also shown that EGF induces increased proliferation in 7 out of 8 other human neuroblastoma cell lines. Functional response of neuroblastoma cells to EGF appears to be a general phenomenon which may be related to a block in the normal maturation pathway of the neural crest cells from which this tumor originates.

Animals↗
PubMed1982

A stochastic model of self-renewal and commitment to differentiation of the primitive hemopoietic stem cells in culture.

We recently identified a murine hemopoietic stem cell colony which consists of undifferentiated (blast) cells and appears to be more primitive than CFU-GEMM in the stem cell hierarchy. The progenitors for the colony which we termed "stem cell colony" possess an extensive self-renewal capacity and the ability to generate many secondary multipotential hemopoietic colonies in culture. We replated a total of 68 stem cell colonies from cultures of murine spleen cells and analyzed the number of stem cell--and granulocyte(neutrophil)-erythrocyte-macrophage-megakaryocyte (GEMM) colony-forming cells in individual stem cell colonies. Of the 68 stem cell colonies, 35 contained progenitors (abbreviated as "S"-cells) for stem cell colonies. The distributions of S-cells and CFU-GEMM in individual stem cell colonies were extremely heterogeneous. Neither the frequency distributions of S-cells nor CFU-GEMM in stem cell colonies could be fitted well by Poisson distribution. Rather, the frequency distribution of the s-cells could be approximated by a geometric distribution and that of CFU-GEMM by an exponential distribution, both of which are variates of the gamma distribution. Our observations are in agreement with those on the distributions of CFU-S in individual spleen colonies and provided support for a stochastic model for stem cell self-renewal and commitment in culture. Application of the theory of the branching process to the distribution of S-cells revealed a distributional parameter "p" of 0.589 which is also in agreement with the earlier report on the p value for reproduction of CFU-S.

Animals↗
PubMed1994

Neuroepithelial endocrine and nervous system in the respiratory tract of Cynops pyrrhogaster with special reference to the distribution of nitric oxide synthase and serotonin.

The respiratory tract of urodeles harbours an intramural nerve network comprising an innervated system of neuroepithelial endocrine (NEE) cells. However, striking differences have been noted between phylogenetically closely related species. Zamboni- or formaldehyde-fixed whole-mount preparations and sections of the saclike lungs of a Japanese salamander, Cynops salamander, Cynops pyrrhogaster, have been investigated for the immunocytochemical detection of nitric oxide synthase (NOS), serotonin (5-HT), VIP, somatostatin, calcitonin, and bombesin; for the enzyme-cytochemical demonstration of NADPH diaphorase (NADPHd); and for formaldehyde-induced fluorescence. In addition, the ultrastructural morphology has been examined by using glutaraldehyde/osmium tetroxide fixed lung tissues. Ovoid 5-HT-immunoreactive (IR) NEE cells occur singly or grouped in the ciliomucous epithelium of the trachea and lungs of Cynops, and a few somatostatin-, calcitonin-, and bombesin-like IR NEE cells are also observed. These cells exhibit a characteristic neuroendocrine morphology as seen with the electron microscope. In addition, large numbers of 5-HT-IR interstitial cells, with round to oval cell bodies and two or three long, slender, sometimes branching processes, are located preferentially along large blood vessels in the connective tissue capsule of the lung and trachea. Immunoelectronmicroscopy shows that 5-HT is localized over large dense granules in the cell bodies and processes of these interstitial cells. NOS-like immunoreactivity occurs in a nerve plexus composed of thick nerve bundles and nerve cells, and in a fine varicose nerve network that originates at least partly from intrapulmonary NOS-containing nerve cells. VIP-like immunoreactivity appears to be colocalized with NOS in the latter network. All NOS-positive nerve fibres in the lungs of Cynops pyrrhogaster and Ambystoma mexicanum stain for NADPHd. It is concluded that the pulmonary NEE cells observed in Cynops pyrrhogaster are similar to those described in other vertebrate species and that the 5-HT-IR interstitial cells resemble mast cells. In addition, nitric oxide is likely to be a bioactive substance involved in nonadrenergic, noncholinergic inhibitory neurotransmission in the pulmonary nervous system of urodeles, where it may be colocalized with VIP.

Amino Acid Oxidoreductases↗
PubMedDate not supplied

Myelin basic protein and transferrin characterize different subpopulations of oligodendrocytes in rat primary glial cultures.

The iron transport glycoprotein, transferrin (Tf), localizes exclusively in oligodendrocytes in brain tissue sections. Previously, we showed that Tf is also expressed in oligodendrocytes in primary cultures established from newborn rat brains. Its developmental appearance precedes that of galactocerebroside (GC). In this study, Tf expression in primary brain cell cultures was investigated over a 4-week period in relation to GC and myelin basic protein (MBP), respectively, early and late markers of oligodendrocyte development. From 9 days in vitro and thereafter, all Tf+ cells were also found to be GC+. With increasing age the number of Tf+ cells decreased while the number of MBP+ cells increased. However, less than 10% of oligodendrocytes co-expressed Tf and MBP at any age. MBP+ cells were largely found in cell clusters which increased in size and number with age in culture. Interestingly, Tf+ cells were located around the clusters of MBP+ cells which displayed elaborate branched processes. The transient expression of Tf in oligodendrocytes which become MBP+, suggests a role for Tf in the early stages of myelinogenesis. The results also demonstrate the existence of three phenotypically distinct populations of oligodendrocytes. A new model of developmental and functional subpopulations of oligodendrocytes is proposed.

Animals↗
PubMed1995

Morphological and molecular response of the MOCH-1 oligodendrocyte cell line to serum and interferon-gamma: possible implications for demyelinating disorders.

The regional loss of oligodendrocytes is thought to be an important pathological event in a variety of demyelinating diseases of the central nervous system (CNS). Various components of serum, which are normally excluded from the CNS by the blood-brain barrier, have been implicated as mediators of demyelinating disorders. We have examined the effects of high concentrations of serum (10% fetal bovine serum, FBS), as well as the cytokine interferon-gamma (IFN-gamma), on an oligodendrocyte cell line, MOCH-1 cells. These cells changed from phase-bright, small round cells with multiple thin, branched processes in 1% FBS medium to flat, fibroblast-like cells with large cell bodies when cultured in 10% FBS medium or 1% FBS medium containing IFN-gamma. These morphological changes were accompanied by a large increase in expression of the astrocyte marker, glial fibrillary acidic protein (GFAP), as detected by Northern and Western blot analyses. In addition, Northern blot and fluorescence-activated cell sorting analyses revealed that IFN-gamma induced a very large increase in major histocompatibility complex (MHC) class I expression in MOCH-1 cells. MHC class II mRNA induction by IFN-gamma was also seen. In contrast, 10% FBS did not elevate either MHC class I or class II mRNA levels in MOCH-1 cells. The morphological and molecular effects of 10% FBS and IFN-gamma were reversible. We suggest that the response of MOCH-1 cells to high concentrations of serum and IFN-gamma may reflect an important in vivo response to oligodendrocytes to perturbations that occur in demyelinating disorders.

Animals↗
PubMed2000

Population extinction and quasi-stationary behavior in stochastic density-dependent structured models.

Density-independent and density-dependent, stochastic and deterministic, discrete-time, structured models are formulated, analysed and numerically simulated. A special case of the deterministic, density-independent, structured model is the well-known Leslie age-structured model. The stochastic, density-independent model is a multitype branching process. A review of linear, density-independent models is given first, then nonlinear, density-dependent models are discussed. In the linear, density-independent structured models, transitions between states are independent of time and state. Population extinction is determined by the dominant eigenvalue lambda of the transition matrix. If lambda < or = 1, then extinction occurs with probability one in the stochastic and deterministic models. However, if lambda > 1, then the deterministic model has exponential growth, but in the stochastic model there is a positive probability of extinction which depends on the fixed point of the system of probability generating functions. The linear, density-independent, stochastic model is generalized to a nonlinear, density-dependent one. The dependence on state is in terms of a weighted total population size. It is shown for small initial population sizes that the density-dependent, stochastic model can be approximated by the density-independent, stochastic model and thus, the extinction behavior exhibited by the linear model occurs in the nonlinear model. In the deterministic models there is a unique stable equilibrium. Given the population does not go extinct, it is shown that the stochastic model has a quasi-stationary distribution with mean close to the stable equilibrium, provided the population size is sufficiently large. For small values of the population size, complete extinction can be observed in the simulations. However, the persistence time increases rapidly with the population size.

Age Factors↗
PubMed1997

Altered immunoreactivity for glial fibrillary acidic protein in astrocytes within 1 h after cervical spinal cord injury.

One hour after a C2 spinal cord hemisection, there are changes in astrocyte morphology and increased glial fibrillary acidic protein immunoreactivity (GFAP IR) near the site of the lesion. Astrocytes adjacent to the lesion display thick, richly branched processes within 1/2 segment rostral and caudal to the level of hemisection. Astrocytes are also enlarged and immunoreactive in gray matter regions of the spinal cord as far caudal as C4 and rostrally to C1. Sham-operated controls, undergoing a laminectomy and durotomy at C2, but not spinal cord hemisection, also exhibit a strong astroglial reaction within 1 h from C1 to C4. However, controls undergoing only a C2 laminectomy do not demonstrate alterations in GFAP IR compared to non-operated controls. The results of this investigation suggest that spinal cord astrocytes are extremely sensitive to both major as well as minor alterations of their microenvironment. Rapid changes in astroglial morphology, as detected by altered GFAP IR, may play a role in changes in neuronal function following spinal cord injury.

Animals↗
PubMed1994

Role of sex steroids on the survival, neuritic outgrowth of neurons, and dopamine neurons in cultured preoptic area and hypothalamus.

Morphological sex differences in some discrete brain regions are thought to be developed by the influence of circulating androgen during the perinatal period. In order to know whether the effect of androgen is a direct one, cells derived from neonatal rat preoptic area (POA) and/or hypothalamus were cultured in a serum-free medium, and the effects on survival, process growth of neurons, and dopaminergic function were examined. When the POA cells were exposed to testosterone (T), neuronal survival was greater than the controls, and the frequency distribution of total process length and the number of process branchings were significantly deviated from the controls. Estradiol-17 beta (E2) and 5 alpha-dihydrotestosterone had less significant effects on these parameters than T. Moreover, the addition of T increased the dopamine (DA) contents of cells and medium DA in the hypothalamic culture. E2 also greatly increased DA content of the medium. These steroids failed to alter the DA levels in the POA cell cultures. These results generally conform to the notion of previous investigators that T has direct effects on the expansion of dendritic elements of the POA and the development of sex difference in the hypothalamic DA neurons, although the effect of T after conversion to E2 cannot be excluded.

Animals↗
PubMed1993

Somatic mutation, monoclonality and stochastic models of stem cell organization in the intestinal crypt.

Among highly proliferating tissues the intestinal tissue is of particular interest. Techniques are available that permit an insight into how intestinal crypts as the basic macroscopic tissue unit are regenerated from a small population of self-maintaining stem cells. However, neither the precise number of these stem cells nor their properties are known. We have recently suggested a model of stem cell organization which explains the life cycle of murine intestinal crypts, their birth (by crypt fission) and extinction rates, as well as their size distribution on a quantitative basis (Loeffler & Grossman, 1991). The model assumptions involve two stochastic branching processes, one for the growth of several independent indistinguishable stem cells and a second for a threshold dependent crypt fission process. New data have now become available challenging the above concept. They relate to the conversion of crypts to monoclonal phenotypic expression after mutagenic events, presumably taking place in single stem cells. A detailed analysis of these data is shown here utilizing a more elaborate version of the above model. The new data are consistent with this model within the range of parameters predicted previously. We conclude that the cellular regeneration of intestinal crypts can be explained on the basis of several indistinguishable stem cells which can replace each other.

Animals↗
PubMed1994

Simple stochastic theory of stem cell differentiation is not simultaneously consistent with crypt extinction probability and the expansion of mutated clones.

It is shown that a simple Galton-Watson branching process model of the stem-cell pool in intestinal crypts is not simultaneously consistent with observations of the dynamics of replacement of normal by mutant crypt stem cells and other observations which put limits on the probability of crypt loss through extinction of all stem cells. This is because the limits on extinction probability forces the probability that a stem-cell division yields only non-stem cells to be small, but such a small probability makes it unlikely that a mutant stem-cell clone would expand while the normal stem-cell clones decay (it is more likely that both normal and mutant clones persist). It is suggested that the fundamental assumptions of independence and constancy of stem-cell behavior are flawed.

Cell Differentiation↗