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D A Steindler

Publications and source records attributed to D A Steindler.

At least 37 records · Page 2Linked to original sources
PubMed1995

Cell and molecular analysis of the developing and adult mouse subventricular zone of the cerebral hemispheres.

The subventricular zone (SVZ) of the lateral ventricle remains mitotically active in the adult mammalian central nervous system (CNS). Recent studies have suggested that this region may contain neuronal precursors (neural stem cells) in adult rodents. A variety of neuronal and glial markers as well as three extracellular matrix (ECM) markers were examined with the hope of understanding factors that may affect the growth and migration of neurons from this region throughout development and in the adult. This study has characterized the subventricular zone of late embryonic, postnatal, and adult mice using several neuronal markers [TuJ1, nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d), neuron-specific enolase (NSE)], glial markers [RC-2, vimentin, glial fibrillary acidic protein (GFAP), galactocerebroside (Gal-C)], ECM markers [tenascin-C (TN-C), chondroitin sulfate, a chondroitin sulfate proteoglycan termed dermatan sulfate-dependent proteoglycan-1 (DSD-1-PG)], stem-cell marker (nestin), and proliferation-specific marker [bromodeoxyuridine (BrdU)]. TuJ1+ and nestin+ cells (neurons and stem cells, respectively) persist in the region into adulthood, although the numbers of these cells become more sparse as the animal develops, and they appear to be immature compared to the cells in surrounding forebrain structures (e.g., not expressing NSE and having few, if any, processes). Likewise, NADPH-d+ cells are found in and around the SVZ during early postnatal development but become more sparse in the proliferative zone through maturity, and, by adulthood, only a few labeled cells can be found at the border between the SVZ and surrounding forebrain structures (e.g., the striatum), and even smaller numbers of positive cells can be found within the adult SVZ proper. BrdU labeling also seems to decrease significantly after the first postnatal week, but it still persists in the SVZ of adult animals. The disappearance of RC-2+ (radial) glia during postnatal development and the persistence of glial-derived ECM molecules such as tenascin and chondroitin sulfate proteoglycans (as well as other "boundary" molecules) in the adult SVZ may be associated with a persistence of immaturity, cell death, and a lack of cell emigration from the SVZ in the adult.

Aging↗
PubMed1995

DNA end labeling (TUNEL) in Huntington's disease and other neuropathological conditions.

Deoxyribonucleic acid of cells undergoing apoptosis is cleaved by a calcium-dependent endonuclease into oligonucleosomal-sized fragments. These fragments can be labeled using the enzyme terminal deoxynucleotidyl transferase so that the cells can be visualized immunohistochemically. Few investigators have evaluated this method in disease processes of the human central nervous system. The Tdt-mediated dUTP-biotin nick end labeling (TUNEL) technique has been investigated in preliminary studies of a variety of pathologic conditions of the human brain (e.g., gliomas, traumatic brain injury, Parkinson's disease, Parkinson's-Alzheimer's complex, multisystem atrophy, striatonigral degeneration). We focus, however, on Huntington's disease (HD) because of the availability of well-characterized pathological stages for study, and also because of the neurodegenerative diseases studied to date, only Huntington's disease revealed significant and consistent labeling with this method. This implies a possibly unique nature to the mechanism of cell death in Huntington's disease compared to the other neurodegenerative diseases studied. TUNEL+ neurons were found in Grade 1-4 HD neostriatum, while labeled astrocytes were found predominantly in the Grade 1 and 2 cases studied to date. TUNEL+ cells were also found in glioblastoma multiforme and traumatic brain injury. We conclude that while there appear to be several limitations associated with this technique, it may be useful for identifying both apoptosis and necrosis in certain neuropathological conditions.

Brain Injuries↗
PubMed1995

Focal brain injury and upregulation of a developmentally regulated extracellular matrix protein.

Tenascin is an extracellular matrix glycoprotein expressed during both normal development and neoplastic growth in both neural and nonneural tissues. During development of the central nervous system (CNS), tenascin is synthesized by glial cells, in particular by immature astrocytes, and is concentrated in transient boundaries around emerging groups of functionally distinct neurons. In the mature CNS, only low levels of the glycoprotein can be detected. The present study demonstrates that following trauma to the adult human cerebral cortex, discrete populations of reactive astrocytes upregulate their expression of tenascin and dramatically increase their transcription of the tenascin gene. The enhanced expression of tenascin may be involved in CNS wound healing, and may also affect neurite growth within and around a brain lesion.

Adult↗
PubMed1995

Tenascin knockout mice: barrels, boundary molecules, and glial scars.

In light of a previous report suggesting that the brains of tenascin-deficient animals are grossly normal, we have studied the somatosensory cortical barrel field and injured cerebral cortex in postnatal homozygous tenascin knockout, heterozygote, and normal wild-type mice. Nissl staining, cytochrome oxidase, and Dil axonal tracing of thalamocortical axonal projections to the somatosensory cortex, all reveal the formation of normal barrels in the first postnatal week in homozygous knockout mice that cannot be distinguished from heterozygote or normal wild-type barrels. In addition to confirming the absence of tenascin in knockout animals, and reporting apparently reduced levels of the glycoprotein in barrel boundaries of heterozygote animals using well-characterized antibodies and immunocytochemistry, we also studied the DSD-1-PG proteoglycan, another developmentally regulated molecule known to be associated with transient glial/glycoconjugate boundaries that surround developing barrels; DSD-1-PG was also found to be expressed in barrel boundaries in apparently normal time frames in tenascin knockout mice. Peanut agglutinin (PNA) binding of galactosyl-containing glycoconjugates also revealed barrel boundaries in all three genotypes. We also examined the expression of tenascin-R, a paralog of tenascin-C (referred to here simply as tenascin). As previously reported, tenascin-R is prominently expressed in subcortical white matter, and we found it was not expressed in the barrel boundaries in any of the genotypes. Thus, the absence of tenascin does not result in a compensatory expression of tenascin-R in the barrel boundaries. Finally, we studied wounds of the cerebral cortex in the late postnatal mouse. The astroglial scar formed, for the most part, in the same time course and spatial distribution in the wild-type and tenascin knockout mice. However, there may be some differences in the extent of gliosis between the knockout and the wild type that warrant further study. Roles for boundary molecules like tenascin during brain pattern formation and injury are reconsidered in light of these findings on barrel development and cortical lesions in tenascin-deficient mice.

Animals↗
PubMed1994

Cells on the edge: boundary astrocytes and neurons.

The caudate-putamen nucleus (neostriatum) is organized as a mosaic of two compartments that during development are cordoned off by astrocytes and associated glycoconjugates. There are complex interactions between these boundary astrocytes and neurons during pattern formation in the neostriatal mosaic, with distinct classes of neurons (such as NADPH-d/NOS cells) residing within boundary as well as nonboundary sites. An hypothesis is presented that implicates glial cells, different classes of neurons, synaptic activity, and neurotoxicity in the shaping of normal cytoarchitectonic and connectional arrangements in the neostriatum. Within such a scenario, special glial cells and neurons are on the edge between compartments, living and dying.

Aging↗
PubMed1993

The complex nature of interactive neuroregeneration-related molecules.

We review the growing list of molecules that may be involved in wound healing in the central nervous system (CNS). It is known that many of these molecules are present during normal development and neoplastic growth in both neural and nonneural tissues, often in areas where pattern formation or tissue remodeling is evident; however, their functional roles are often quite elusive. In order to understand the changes that occur in and around a brain wound, we review proposed functions of neuroregeneration-related molecules in in vitro and in vivo preparations, as well as note their expression in other healing tissues including skin. A hypothesis that wound healing events in the CNS supersede neuritic growth around a lesion is presented. In contrast to the classical view of failed regeneration, there may be significant amounts of circuit reorganization that occur following injury, and such plasticity may be further enhanced by manipulating the molecular environment around a brain wound and in synaptically related structures.

Animals↗
PubMed1992

Enhanced expression of the developmentally regulated extracellular matrix molecule tenascin following adult brain injury.

Tenascin is an extracellular matrix molecule synthesized and released by young astrocytes during embryonic and early postnatal development of the nervous system, and it is concentrated in boundaries around emerging functional neuronal units. In the adult nervous system, tenascin can be detected only in very low levels. Distinct spatial and temporal distributions of tenascin during developmental events suggest a role in the guidance and/or segregation of neurons and their processes within incipient functional patterns. We show here, using in situ hybridization and immunocytochemistry, that stab wounds of the adult mouse cerebellar and cerebral cortices result in an enhanced expression of tenascin in a discrete region around the lesion site that is associated with a subset of glial fibrillary acidic protein-positive astrocytes. Tenascin up-regulation in the lesioned adult brain may be directly involved in failed regeneration or indirectly involved through its interactions with other glycoconjugates that either inhibit or facilitate neurite growth.

Age Factors↗
PubMed1992

Afferent-boundary interactions in the developing neostriatal mosaic.

The caudate-putamen (neostriatum) of the mammalian basal ganglia is composed of two neurochemically distinct compartments termed patch (island, striosome) and matrix that overall contribute to a mosaic organization. In the present study, the distribution of the developmentally regulated extracellular matrix molecule tenascin, as well as several other neural cell adhesion molecules, was examined in the neostriatal mosaic of the early postnatal mouse and compared with tyrosine hydroxylase distribution following partial destruction of the dopaminergic nigrostriatal projection. During normal neostriatal development, tenascin is most dense within the matrix compartment and highly concentrated in boundaries around patches. This pattern is apparent on embryonic day 18, and for the most part disappears by postnatal day 12. Tenascin immunoreactivity is altered in the neostriatum following lesions of the nigrostriatal pathway in the first postnatal week revealed by an overall reduced expression of this molecule and a marked reduction in tenascin staining of boundaries at the interface of tyrosine hydroxylase-rich patch and tyrosine hydroxylase-poor matrix compartments. When compared to tyrosine hydroxylase immunoreactivity, other cell adhesion molecules tested failed to show altered intensities and patterns of immunoreactivity within the neostriatum after similar lesions. Reduced levels of tenascin in the lesioned neostriatum, in register with altered levels of tyrosine hydroxylase immunostaining of dopaminergic inputs, suggests that axons may affect the expression of particular recognition molecules in their target structures. The fact that boundaries are malleable can be related to afferent-induced plastic events in the differentiation of cellular elements in the developing nigrostriatal system.

Animals↗
PubMed1991

Boundaries and wounds, glia and glycoconjugates. Cellular and molecular analyses of developmental partitions and adult brain lesions.

During brain development, transient partitions of glia and glycoconjugates (glycoproteins, glycolipids, and glycosaminoglycans) surround forming functional units (e.g., nuclear divisions, whisker-related barrels, and neostriatal striosomes). These partitions, which we think of as boundaries, consist of dense aggregates of glial fibrillary acidic protein (GFAP)-positive radial glia, young astrocytes and their processes, and developmentally regulated glycoconjugates (e.g., J1/tenascin and the 473 proteoglycan) that can be thought of as recognition molecules present on membranes or perhaps within the extracellular matrix. When functional patterns have formed and appear to be stabilized, these boundaries are no longer detectable. Lesions of the developing brain show the existence of a more global astrocytic distribution suggestive of biochemically distinct subsets of astrocytes that reside within boundary versus nonboundary positions. Lesions of the adult brain, in addition to showing gliosis, reveal a reexpression of some of the same macromolecules present in transient brain boundaries during development. It is postulated that developmental boundaries and wounds in the adult brain possess some of the same inhibitory and possibly alluring molecular substrates for neuritic expansion.

Aging↗
PubMed1990

Molecular and cellular characterization of the glial roof plate of the spinal cord and optic tectum: a possible role for a proteoglycan in the development of an axon barrier.

Certain types of glial structures, located at strategic positions along axon pathways, may provide the mechanical and/or chemical elements for the construction of barriers which can grossly direct the elongation of axons during development. The roof plate, a putative axon barrier, is located along the dorsal midline of the developing spinal cord and may be important for the guidance of the commissural and dorsal column axons. We examined the roof plate to determine the developmental morphology of the region and to determine which molecules were correlated with the barrier function when axons were growing nearby. Light and electron microscopic observations of the roof plate revealed that this glial domain undergoes a dramatic change in shape from a "wedge" with large extracellular spaces between the cell apices at E12.5 to a thin, dense septum with reduced extracellular space at E15.5. Immunocytochemical techniques demonstrated that highly sialylated neural cell adhesion molecule (N-CAM), the carbohydrate recognized by L2 monoclonal antibody, cholinesterase, stage-specific embryonic antigen 1, and a ligand that binds tetragonolobus purpureas agglutinin are expressed by the roof plate. These molecules, however, were also found in other regions of the spinal cord which are permissive or attractive to axon growth. A molecule which is unique to the roof plate when axons grow close to, but do not cross, the dorsal midline is a glycosaminoglycan (GAG), keratan sulfate. Keratan sulfate is also present in the tectal midline and in other noninnervated regions such as the outer epidermis and developing cartilage. Our data suggest that keratan sulfate, alone or in combination with other molecules expressed by the roof plate, may be responsible, in part, for the inhibition of axon elongation through the roof plate in the embryonic spinal cord.

Animals↗
PubMed1990

Boundaries during normal and abnormal brain development: in vivo and in vitro studies of glia and glycoconjugates.

This paper focuses on transient boundaries of glia and glycoconjugates during development of the mouse central nervous system (CNS). Lectin-bound glycoconjugates, glial fibrillary acidic protein, and the J1/tenascin glycoprotein are distributed coextensively within boundaries around developing substructural arrangements (e.g., developing nuclei, and at a finer level, somatosensory cortical "barrels" related to individual facial vibrissae) throughout the CNS during pattern formation events. Electron microscopy has shown that the J1/tenascin glycoprotein, for example, is present in immature astrocytes, on glial and neuronal plasma membranes, and within the pericellular space that could be extracellular matrix (ECM). The findings presented on the expression of this well-characterized ECM molecule suggest that previously described glial and glycoconjugate boundaries reported by our group are in part composed of specific recognition molecules. The J1/tenascin glycoprotein, a chondroitin sulfate-containing antigen termed the 473 proteoglycan, and the adhesion molecule on glia are expressed within discrete boundary regions and associated axonal pathways. There, they may sculpture fine aspects of functional cytoarchitectonic arrangements and help guide axons to specific targets. The expression and developmental regulation of glycoproteins such as J1/tenascin may thus be integral events during pattern formation and synaptogenesis in the CNS. The presence of abnormal glial arrangements and glycoconjugate boundaries in the cortices of the genetic mutant mouse reeler, and findings on plasticity of boundaries following various perturbations, suggest that boundary expression is controlled by both genetic and epigenetic factors. Some future directions for studying developmental boundaries, including use of cultured explants for in vitro "bioassays," are also discussed.

Aging↗
PubMed1989

Critical period-dependent alterations of the transient body image in the rodent cerebral cortex.

The present study demonstrates that the boundary patterns of cell surface-associated molecules detected with lectins in the barrel cortex of neonatal rodents are altered, as are the boundary patterns of cortical glia, following perturbation of large vibrissae in the contralateral mystacial face pad. The alterations in the transiently expressed molecular patterns of lectin-receptors provide data that are consistent with the idea that the periphery plays a prominent role in the establishment of functional cytoarchitecture in the developing cortex. The data are also consistent, however, with the notion that factors intrinsic to the cerebrum, such as the immature cortical glial cells, are of considerable importance in this respect and a direct or indirect interaction of thalamocortical afferents with glial cells in the somatosensory cortex of the neonate are indicated. It is suggested therefore that a critical period in early barrel development, a time in which the cortical neuronal architecture is malleable in response to altered afferent input, is directly related to the presence of these cellular and molecular boundaries. The transient barrel boundaries, it is argued, are the morphological and molecular substrates that form the physical basis of the critical period.

Afferent Pathways↗
PubMed1989

Two types of locus coeruleus neurons born on different embryonic days in the mouse.

Retrograde axonal tracing studies were performed in combination with tritiated thymidine cell birthday analyses in order to determine whether or not any hodologicotemporal gradients exist in neuron genesis within the murine locus coeruleus. Following injections of retrograde tracers within the forebrain or cerebellum in mice exposed in utero to the radiolabeled nucleoside on embryonic days 9-11 (E9-11), combined histochemical and autoradiographic preparations revealed: 1) Locus coeruleus neurons that give rise to long distance axonal projections to the cortices are born exclusively on E9 (other studies indicate that these cells are noradrenergic); and 2) Locus coeruleus cells born on E10 and E11 are a class of smaller cells which were never observed to project to distant structures. The transmitters of these apparent local circuit neurons have not yet been determined, but gamma aminobutyric acid is one possible candidate. These findings support the interpretation that monoaminergic neurons tend to arise earlier during development than non-monoaminergic neurons within the locus coeruleus, and that distinctly different connectional arrangements exist for these monoaminergic and non-monoaminergic cells.

Animals↗
PubMed1989

Boundaries defined by adhesion molecules during development of the cerebral cortex: the J1/tenascin glycoprotein in the mouse somatosensory cortical barrel field.

The distribution of the 200/220 KDa J1 glycoprotein (J1-200/220), within the developing vibrissae-related barrel field of the mouse somatosensory cortex, was studied by immunocytochemistry using a monoclonal antibody. J1-200/220, a member of the L2/HNK-1 family of adhesion molecules, also appears to be the mouse homologue of tenascin. J1/tenascin-positive barrel-like structures are visible in the somatosensory cortex between 24 and 48 hr after birth, with the molecule present in prospective barrel boundaries. Immunoelectronmicroscopy reveals labeling that is associated with glial and neuronal plasma membranes, as well as glial end-feet on blood vessels. A possible major source of J1/tenascin expression at this time is astrocyte precursor cells and radial glia. In the putative astrocyte precursor cells, immunolabeling was observed within organelles including the Golgi apparatus. At P6-7 J1/tenascin is most prevalent within prospective interbarrel septae. J1/tenascin-positive barrel boundaries are barely visible on P9 and not observed on P16. The findings indicate that J1/tenascin represents a major component of previously described "hidden" boundaries that we have seen during development using other methodologies. The expression of adhesion molecule-rich boundaries during the critical stages of barrel field formation indicates roles for such molecules during specific cerebral cortical pattern formation events.

Animals↗
PubMed1988

Glycoconjugate boundaries during early postnatal development of the neostriatal mosaic.

The dispositions of galactosyl-containing glycoconjugates were studied during postnatal development of the caudate putamen in mice. The binding of the lectin peanut agglutinin, which has an affinity for galactosyl B-1,3 N-acetylgalactosamine residues, was compared to acetylcholinesterase staining and tyrosine hydroxylase immunoreactivity in the immature and adult neostriatum. The binding of peanut agglutinin conjugated to horseradish peroxidase, in sections that were processed for peroxidase histochemistry, was extremely pronounced in the neostriatum through the first postnatal week and constituted ringlike or polygonally shaped structures, which, overall, produced a variegated mosaic. These structures consist of outer rims of dense lectin-associated reaction product surrounding lightly labeled centers. Lectin delineations of the neostriatal mosaic are no longer visible in the second postnatal week. When adjacent sections were processed for lectin binding or acetylcholinesterase histochemistry, the dense lectin binding sites represented borders of acetylcholinesterase-rich and -poor zones. The distribution of dense patches of tyrosine hydroxylase immunoreactive fibers and terminals also coincides with the acetylcholinesterase-rich zones during the same times, and thus the glycoconjugate-delineated boundaries can also be directly compared with the distribution of nigrostriatal dopaminergic projections. The findings presented here represent the first demonstration of a probe that recognizes apparent borders of neostriatal compartments during a limited period of development. They are consistent with previous observations made on transient glycoconjugate "hidden boundaries" during development of other central nervous system structures, including the somatosensory cortical barrel field, and thalamic and brainstem nuclei (Cooper and Steindler, '86a,b; Steindler and Cooper, in press). In those studies, glia were shown to be the major source of glycoconjugate-associated patterns, and thus, glia and glycoconjugates that they synthesize during pattern formation events may be involved in the formation and stabilization of neurochemically distinct components of the neostriatal mosaic.

Acetylcholinesterase↗
PubMed1987

Glial and glycoconjugate boundaries during postnatal development of the central nervous system.

The localization of glycosylated molecules and glia has been studied during early postnatal development in the mouse central nervous system (CNS) using autoradiographic detection of radiolabeled fucose incorporation, and in sections processed either for histochemistry or immunocytochemistry following binding of labeled lectins or an antibody to glial fibrillary acidic protein. Radiolabeled sugar incorporation, lectin binding of glycoconjugates, and glial labeling all reveal borders between nuclei within the diencephalon, midbrain, and brainstem through the first postnatal week. Glycoconjugate and glial boundaries exist throughout the CNS during pattern formation events, and they also are seen in relation to fine aspects of developing functional organization within individual structures (e.g. segmentation associated with the representation of mystacial vibrissae within the brainstem trigeminal complex). The observation that each of the probes employed in this study fails to label boundary organization during later postnatal times suggests that the distribution and chemistry of the glial/glycoconjugate network are dynamic, and they change in accordance with distinct maturational states of the nervous system.

Animals↗
PubMed1987

Abnormal glial and glycoconjugate dispositions in the somatosensory cortical barrel field of the early postnatal reeler mutant mouse.

During early postnatal development in reeler mutant mice, lectin binding delineates prospective abnormal barrels as they will appear in the adult mutant somatosensory cortex. Glial fibers also may be more condensed within fascicles in developing reeler barrels. These fibers also appear to be misaligned, coursing predominantly in the tangential plane within the abnormal reeler barrel sides as opposed to having a radial orientation as seen in normal mouse barrels. The thalamic barreloid complex, however, reveals a disposition of glycoconjugates that is completely normal in reeler. Thus, there are anomalies in glia and associated glycoconjugates during mainly cortical development in the reeler mutant mouse that might be related to the primary action of the abnormal gene.

Animals↗