PubMed Health⌕ Search

Biomedical subjects

R S Nowakowski

Publications and source records attributed to R S Nowakowski.

17 recordsLinked to original sources
PubMed1992

Cytoarchitectonic abnormalities in hippocampal formation and cerebellum of dreher mutant mouse.

The laminated structures in the hippocampal formation and cerebellum of homozygous dreher mice were compared to their littermates and to C57BL/6J mice in Nissl- and myelin-stained preparations. In the dreher dentate gyrus, ectopic granule cells were situated in the molecular layer, and frequently there was either partial or complete absence of the infrapyramidal limb of the granule cell layer. In the dreher hippocampus, the cells of the pyramidal cell layer in area CA3 formed widely dispersed arrangements, and there were ectopically situated pyramidal cells in the stratum radiatum and stratum oriens. In the dreher cerebellum, 3 abnormal patterns were observed: (1) disruptions of foliation with normal cytoarchitectonic structure, (2) foliation with a mixture of normal laminated structure and abnormal laminated structure, and (3) almost complete absence of the cerebellum. In abnormal folia exhibiting the second or third pattern, islands consisting of agglomerations of both granule cells and Purkinje cells or just granule cells were observed. The neuronal heterotopias and cytoarchitectonic disorganization observed in the present study are apparently secondary to disruption of cell proliferation and neuronal migration produced directly or indirectly by the dreher mutation. In addition, the fact that the phenotypic abnormalities in homozygous dreher mice produces different abnormal morphologies in different specimens may be useful for analyzing the development of the hippocampal formation and cerebellum.

Animals↗
PubMed1992

Competitive interactions during dendritic growth: a simple stochastic growth algorithm.

A simple growth algorithm is presented that deals with one feature of dendritic growth, the distance between branches. The fundamental assumption of our growth algorithm is that the lengths of dendritic segments are determined by the branching characteristics of the growing neurite. Realistic-appearing dendritic trees are produced by computer simulations in which it is assumed that: (1) growth of individual neurons occurs only at the tips of each growing neurite; (2) the growing neurite can either branch (as a bifurcation) or continue to elongate; (3) events at any one growing tip do not affect the events at any other growing tip; and (4) the probability of branching is a function only of the distance grown either from the cell body (if branching has not occurred) or from the previous branch point. An analytic solution of a differential equation based on these same assumptions produces a distribution of dendritic segment lengths that accurately fits an experimentally determined distribution of dendritic segment lengths of reconstructed neurons, accounting for about 89% of the sample variance. Our analysis indicates that, immediately following branching, the temporary suppression of further branching during dendritic growth may be an important mechanism for regulating the distance between branches.

Algorithms↗
PubMed1992

BUdR as an S-phase marker for quantitative studies of cytokinetic behaviour in the murine cerebral ventricular zone.

BUdR incorporation into replicating DNA, detected immunohistochemically, is used as an S-phase marker in the proliferative cell populations of the cerebral wall of the mouse embryo on the 14th gestational day (E14). The analysis initiates a series of studies concerned with the cytokinetic behaviour and cell output of proliferative populations involved in neocortical histogenesis. On E14 there are two periventricular proliferative zones in the cerebral wall. These are the ventricular and subventricular zones. The ventricular zone is a pseudostratified epithelium. DNA replication occurs with the cell nucleus in the outer zone of the epithelium and mitoses at the ventricular surface. Prior applications of BUdR for studies of cytogenesis in the CNS have been extended in two principal ways: (1) basic fuchsin was used as counterstain for BUdR-negative nuclei and (2) labelling indices were determined separately in strata or bins, 10 microns in height, through the full depth of the ventricular zone and overlying cerebral wall. It was established that a single injection of 50 micrograms g-1 into the pregnant dam was associated with labelling of 100% of nuclei in S-phase over an interval extending from 15 min to at least 2.0 h after injection. The zone where nuclei are undergoing S-phase (S-phase zone) extends through the outer four bins of the ventricular zone. The method has high quantitative reproducibility with an SE for labelling indices in bins within the S-phase zone less than 10% of the average values. Evidence is provided that BUdR incorporation is initiated with the nucleus in the outer aspect of the S-phase zone. The efficiency of incorporation of the marker is reduced as nuclei near the end of DNA replication and move to the inner aspect of the S-phase zone.

Animals↗
PubMed1991

Abnormalities of foliation and neuronal position in the cerebellum of NZB/BINJ mouse.

To analyze developmental abnormalities related to neural migration in the NZB/BINJ mouse, the pattern of cerebellar foliation and neural position were compared with that of a normal mouse (C57BL/6J). Three abnormalities of cerebellar foliation--(1) lobe isolated from other cerebellar lobes, (2) lobes imbalanced in relative amounts or ratio of granular cell layer and molecular layer, (3) lobes in which some Purkinje cells and the molecular layer was embedded in the granular cell layer--were observed in NZB/BINJ mice. These morphological abnormalities were not limited to a specific lobe. On the other hand, abnormalities of neural position were observed in both granule and Purkinje cells. The pattern of ectopically-situated granule cells, in general, could be divided into 3 types: (1) large cell clusters extending from granular cell layer to the pia mater or middle part of the molecular layer, (2) clusters of various sizes scattered within the white matter and (3) clusters formed by combination of granule cells extending from two opposed granular cell layers to the molecular layer. The pattern of ectopically-situated Purkinje cells could be divided into 4 types: (1) ectopia of a group of cells from one part of the Purkinje cell layer, (2) ectopia of a single Purkinje cell observed in the molecular layer, (3) single Purkinje cell scattered within the white matter accompanied by clusters of ectopic granule cells and (4) ectopic Purkinje cells embedded in the granular cell layer. The abnormalities in position of both granule cells and Purkinje cells was not limited to a particular cerebellar lobe.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Glial cell differentiation in neuron-free and neuron-rich regions. I. Selective appearance of S-100 protein in radial glial cells of the hippocampal fimbria in human fetuses.

The proliferative cells of the developing hippocampal fiber tract fimbria have only the potential for gliogenesis; thus the developing fimbria provides an ideal model for the study of the development and differentiation of its constituent glial cells. In the first stage of development, the fimbrial primordium can be distinguished morphologically, and during the second stage, the fimbria becomes a well-defined fiber tract. In the third stage, a divergent immunocytochemical staining pattern clearly demarcates the neuron-free fimbria from the hippocampus, where a mixed neuro- and gliogenesis occurs. The distinct expression of S-100 protein in radial glial cells is restricted to the fimbria. During the final stage of development, the ventricular lining of the fimbria will mature into an ependyma. It is suggested that the S-100-positive radial glial cells of the fimbria, which probably retain their proliferative capacity, represent a homogeneous population of precursor cells that will give rise to the glial cells of the adult fimbria. The appearance of S-100 in the fimbrial radial glial cells seems to occur coincidentally with the establishment of hippocampal commissural connections. The S-100-positive radial glial cells of the fimbria may guide and segregate populations of growing axons by providing physical and chemical cues. Thus, S-100 protein per se seems to be intimately involved in modulation and regulation of axonal growth and patterning.

Axons↗
PubMed1991

Glial cell differentiation in neuron-free and neuron-rich regions. II. Early appearance of S-100 protein positive astrocytes in human fetal hippocampus.

The development of the human fetal hippocampus and dentate gyrus has been studied immunocytochemically. The first glial cells to appear are vimentin-positive radial glial cells. A gradual transition from vimentin to glial fibrillary acidic protein (GFAP) reactivity in the radial glial cells occurs at week 8. The GFAP-positive radial glial cells transform into astrocytes from week 14. A population of small S-100-positive somata which morphologically and spatially are distinct from GFAP-positive radial glial cells and their transformed progeny, are found as early as week 9.5 in the hippocampus during the period of peak neurogenesis. The well-defined immunoreactivity of the morphologically homogenous cell subpopulation for S-100 protein, which has been used as an astrocytic marker in the adult hippocampus, indicates that astrocytes may differentiate at very early gestational ages in human fetuses. The S-100-positive astrocytes are thought to be derived from ventricular zone cells, which at the time of their appearance do not express any of the applied astrocytic markers (S-100, GFAP, vimentin). It is suggested that the S-100-positive astrocytic cell population interacts with the first incoming projection fibers, so modulating the pattern of connectivity.

Astrocytes↗
PubMed1991

Left out axons make men right: a hypothesis for the origin of handedness and functional asymmetry.

The origin and underlying mechanisms of hand preference are still unresolved, despite extensive research and discussion. Numerous possibilities have been considered, including genetic and hormonal factors, brain insult and learning. We suggest here that naturally occurring loss of axons of the corpus callosum (either symmetric or asymmetric, with or without neuron death) may be one mechanism underlying the embryological development of hand preference and hemispheric anatomical and functional asymmetries in males. We note supporting evidence for this hypothesis from a report of increased prevalence of left-handedness in children born prematurely at the gestational age prior to the likely onset of axon loss. The practical implications of this hypothesis for clinical management in neonatal intensive care units are discussed. It is suggested that the course of loss of callosal axons may have a genetic component which is associated with a sex-related influence and which is modifiable by prenatal and early postnatal events.

Axons↗
PubMed1991

Effect of prenatal exposure to ethanol on the cell cycle kinetics and growth fraction in the proliferative zones of fetal rat cerebral cortex.

Prenatal exposure to ethanol produces profound changes in the number of neurons in the mature cortex. These changes in neuronal number may reflect ethanol-induced disturbances in early developmental processes, that is in the proliferation of neuronal precursors. Hence, the present study examined the effect of ethanol on cell proliferation in the two neocortical proliferative zones, the ventricular zone (VZ) and subventricular zone (SZ). From gestational day 5 to 21, pregnant rats were fed an ethanol diet (6.7% v/v), pair-fed an isocaloric control diet, or fed chow and water. Pregnant rats were given a series of one to nine injections of bromodeoxyuridine (BrdU). After immunohistochemical processing, the ratio of cells in each proliferative zone that were labeled with BrdU to the total population was determined. The portion of the population that was cycling (growth fraction), the total length of the cell cycle, and the length of the S-phase of the cell cycle were calculated for VZ and SZ cells. Exposure to moderate levels of ethanol has markedly different effects upon the two neocortical proliferative zones. In the VZ, the length of the total cell cycle was significantly greater in ethanol-treated rats than in controls; however, the growth fraction and the length of the S-phase were unaffected by ethanol. In contrast, in the SZ, the growth fraction was significantly greater in ethanol-treated rats, but ethanol had no effect on the length of the total cell cycle or of the S-phase. These differences may underlie the ethanol-induced abnormalities in neuronal generation.

Animals↗
PubMed1990

Heterozygote effects in dreher mice.

The dreher mutation (gene symbol: dr) is an autosomal recessive mutation located on chromosome 1 of the mouse. Homozygous dreher mice (dr/dr) are ataxic, have a white belly spot, a short-tail, inner ear and skeletal malformations, and a variety of CNS abnormalities. Recently in our dreher colony (the drsst-J allele on a B6C3Fe background), we noticed mice with one or more white belly spots typical of drsst-J/drsst-J mice but which were non-ataxic and had a normal tail length; wild-type mice (+/+) of the same genetic background do not have simialr belly spots. Results of three breeding experiments indicate that a new mutation had not occurred, but rather that the spotted, non-ataxic mice are heterozygous dreher mice (drsst-J/+). Histological examination showed that drsst-J/+ mice have abnormalities in the hippocampal formation that are qualitatively similar to those found in drsst-J/drsst-J mice. Most frequently there is an increase in the number of pyramidal cells in CA3 and a marked thickening of the pyramidal cell layer. In contrast to dreher homozygotes the cerebellum appears to have a normal foliation pattern and no discernible laminar abnormalities. Thus, both breeding experiments and histological examination indicate that drsst-J is semidominant. We speculate that drsst-J is a "loss of function" mutation, but, in any event, the presence of phenotypic abnormalities in drsst-J/+ mice may be useful in identifying the primary developmental defect in dreher mice.

Animals↗
PubMed1989

Bromodeoxyuridine immunohistochemical determination of the lengths of the cell cycle and the DNA-synthetic phase for an anatomically defined population.

A cumulative labelling protocol using 5-bromo-2'-deoxyuridine (BUdR) was followed to determine: (1) the growth fraction (i.e., the proportion of cells that comprise the proliferating population), (2) the length of the cell cycle, and (3) the length of the DNA-synthetic phase (S-phase) for proliferative cells in the dentate gyrus of the mouse. On postnatal day 20 (P20), C57BL/6J mice were injected with BUdR at two hour intervals for a total period of 12 hours. Animals were sacrificed at selected intervals, and the brains were processed for immunohistochemistry using a monoclonal antibody directed against single-stranded DNA containing BUdR. The numbers of BUdR-labelled and unlabelled cells in sections through the hilus of the dentate gyrus were counted. The number of BUdR-labelled cells increased linearly from an initial value of about 12% of the total number of cells to a maximum value of just over 24% of the total. These findings indicate that, at P20, a maximum of 24.2 +/- 1.2% of the cells in the dentate hilus are part of the proliferating population. The calculated length of the cell cycle of the cells comprising the intrahilar proliferative zone was estimated to be 16.1 +/- 0.8 h. The length of the S-phase was estimated at 8.0 +/- 0.4 h. In addition, mathematical analysis, using one and two population models, indicates that over 90% of the proliferating cells in the dentate hilus at this age comprise a single population at least in terms of the lengths of the cell cycle and the S-phase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Use of bromodeoxyuridine-immunohistochemistry to examine the proliferation, migration and time of origin of cells in the central nervous system.

The use of an exogenously administered thymidine analog, 5-bromo-2'-deoxyuridine (BrdU), for studies of the proliferation, migration and time of origin of cells in the cerebral cortex was investigated and compared with [3H]thymidine [( 3H]dT) autoradiography. Pregnant rats or mice were injected with BrdU and/or [3H]dT and processed by standard immunohistochemical techniques using a primary antibody directed against BrdU in single-stranded DNA, autoradiographic methods, or both. In animals that survived only 1 h after the injection, BrdU-positive cells were distributed in the proliferative zones throughout the central nervous system (CNS). In animals killed 1-3 days after the BrdU injection, intensely immunoreactive cells were in the superficial cortical plate and less intensely labeled cells were scattered throughout the deep cortical plate, the intermediate zone, and the germinal zones. In adult animals, 60 days or more after an injection of BrdU on GD 19, BrdU-positive cells were located in layer II/III of neocortex, the hippocampal pyramidal layer, and the granule layer of the dentate gyrus. In the double-labeling studies, the distribution of BrdU-immunoreactive cells was identical to that of autoradiographically labeled cells, and all autoradiographically labeled neurons were BrdU positive. Thus, BrdU immunohistochemistry is suitable for developmental studies of the CNS; moreover, it provides several advantages over [3H]dT autoradiography.

Animals↗
PubMed1987

Genetic factors and the measurement of exploratory activity.

The progenitor strains C57BL/6 and BALB/c and the seven recombinant inbred strains derived from them were used to examine the genetic relationship between two measures of activity and hippocampal lamination defect (Hld). Fifty-three mice (Mus musculus), 9 from each of the progenitor strains and 5 from each recombinant inbred strain, were tested for 16 min in a device which permitted both unobstructed traverse of the length of a runaway and contact with objects which were aligned alongside the runway. The C57BL/6 mice produced significantly more locomotor (runway traversal) activity, whereas the BALB/c showed significantly greater amounts of investigatory (object contact) activity. This reversal of relative position in the distribution of scores was not present for the recombinant strains. There was no dichotomous separation of recombinant strains for either measure. Examination of activity in terms of four consecutive 4-min periods indicates differences among the strains with respect to changes during the test session. The strains may be dichotomized with respect to decrement in activity within the 16-min session, but these groups do not correspond with those reported by others. The inference of a single genetic determinant for activity measured either as locomotor or investigatory responses is not supported by these data, nor is there any apparent relationship between activity and Hld. The critical influence of genetic-environment interactions in determining behavior and the effect of the selection of measurement techniques upon interpretation of data are emphasized by these data.

Animals↗
PubMed1987

Basic concepts of CNS development.

Some basic principles of the development of the central nervous system (CNS) are reviewed and their implications for both normal and abnormal behavioral development are discussed. The goals of this review are: to provide a set of concepts to aid in the understanding of the variety of complex processes occurring during CNS development, to illustrate how these concepts contribute to our knowledge of the normal anatomy of the adult brain, and to delineate how modifications of normal developmental processes by traumatic injury, by environmental or experiential influences, or by genetic variations may lead to modifications in the resultant structure and function of the adult CNS.

Brain↗
PubMed1985

Dendritic arbors and dendritic excrescences of abnormally positioned neurons in area CA3c of mice carrying the mutation "hippocampal lamination defect".

BALB/cJ and BALB/cByJ mice are homozygous for the autosomal gene "hippocampal lamination defect" (provisional gene symbol: Hld) which produces an abnormality in the lamination of the pyramidal cell layer of area CA3c of the hippocampus such that early-generated neurons are superficial and late-generated neurons are deep. Other inbred strains of mice are wild-type (+/+) at the Hld locus and do not have this inversion in cell position in area CA3c. The Golgi method was used to analyze the dendritic arbors of the abnormally positioned pyramidal cells and to compare the distribution of dendritic excrescences (i.e., the termination sites of the mossy fibers) in +/+ and Hld/Hld mice. It was found that in +/+ mice the late-generated pyramidal cells (whose cell bodies are positioned just below the suprapyramidal mossy fiber layer) have one set of dendritic excrescences on their apical dendrites as they extend through the suprapyramidal mossy fiber layer and a second set on their basal dendrites as they pass through the infrapyramidal mossy fiber layer. In contrast, in Hld/Hld mice the late-generated pyramidal cells (whose cell bodies are abnormally positioned just below the intrapyramidal mossy fiber layer) have two sets of dendritic excrescences on their apical dendrites, as they pass through the intrapyramidal and suprapyramidal mossy fiber layers, and none on their basal dendrites. In addition, in the vicinity of the apparent point of contact of the intrapyramidal mossy fibers, the apical dendrites of some of the abnormally positioned pyramidal cells have several fine-caliber branches.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1979

The mode of migration of neurons to the hippocampus: a Golgi and electron microscopic analysis in foetal rhesus monkey.

The mode of neuron migration from the site of their origin in the ventricular zone to area CA1 of the hippocampus was analysed with Golgi and electron microscopic methods during the first half of gestation in the foetal rhesus monkey. In the inner portion of the intermediate zone, the migrating cells have a bipolar form with one, or oaccasionally two, leading processes which do not reach the ammonic plate and with a single trailing process which usually ends within the intermediate zone. Both the nucleus and the cytoplasm of the migrating cells are relatively electron-dense and the latter contains organelles typical of young neurons as described in other brain regions. Analysis of electron micrographs from serial sections reveals that the length of the somata and of the leading and trailing processes of the migrating neurons is apposed to fascicles of radially oriented, electron-lucent, microtubule-filled fibres which are ultrastructurally similar to the radial glial fibres of the neocortex and to the Bergmann glial fibres of the cerebellum. The close (20 nm) apposition between the membranes of the migrating cell and the radial fibre is maintained even in areas where the fibres bend or curve tortuously. Migrating neurons situated at progressively more superficial levels of the intermediate zone become progressively more differentiated and complex. Thus, in the outer portion of the intermediate zone, the migrating cells acquire several additional cytoplasmic processes and occasionally a long thin axon-like process which courses into the incipient alveus. These cells have somewhat larger somata and less electron-dense nuclei and cytoplasm than the migrating neurons still situated in the inner part of the intermediate zone. Cells close to the ammonic plate usually have one to three cytoplasmic processes that enter the ammonic plate and terminate near their presumed final position. Migrating neurons situated at the lower border of the ammonic plate have a single large apical process which intermingles with neurons already in their final position and which sometimes traverses the ammonic plate. The apposition of the migrating neurons to the radial glial processes becomes less explicit as the cell soma enters the ammonic plate, reflecting the more complex three-dimensional intercellular relationships. However, the present analysis indicates that during the middle and late stages of neuronal migration to the hippocampus radial glial fibres may guide postmitotic young neurons across the intermediate zone to the ammonic plate in the same way that they guide neurons migrating to the superficial and middle layers of the neocortical plate.

Animals↗