bluuebunny/crossref_metadata_2025 huggingface dataset:
Ontogeny of apomorphine‐induced stereotypy and its D1 and D2 receptor mediation in rats depleted of dopamine as neonates
Authors: Abrams Dalia R. , Bruno John P.
Published: January 2005

The ontogeny of apomorphine‐induced stereotypy in rats treated with 6‐OHDA (100 μg) or its vehicle on postnatal Day 3 was determined on Days 6, 21, or 60–90. Stereotypic sniffing and mouthing behavior were produced by apomorphine in control and DA‐depleted animals as early as Day 6. Animals depleted of DA as neonates exhibited supersensitivity to these behavioral effects from Day 6 into adulthood. The relative contributions of D1 and D2 receptor activation to apomorphine‐induced behaviors were determined by measuring the ability of specific D1 or D2 antagonists to block these effects in adults. Blockade of D1 receptors with SCH 23390 or D2 receptors with clebopride suppressed apomorphine‐induced stereotypy in both vehicle‐ and 6‐OHDA‐treated rats. However, adults depleted of DA as neonates were less sensitive to the DA antagonists than were control rats. These results demonstrate that apomorphine‐induced stereotypy is present as early as postnatal Day 6. Rats depleted of DA as neonates continue to exhibit these behaviors, even at lower doses of apomorphine than were necessary in control animals. Finally, coactivation of D1 and D2 receptors appears necessary for apomorphine‐induced stereotypy in both groups of rats. © 1992 Wiley & sons. Inc.
Thermogenesis during ultrasonic vocalization by rat pups isolated in a warm environment: A thermographic analysis
Authors: Blumberg Mark S. , Efimova Inna V. , Alberts Jeffrey R.
Published: January 2005

Ultrasonic vocalizations, emitted by rat pups when separated from their mother, littermates, and home cage, have been used as a measure of isolation distress. Recently, we demonstrated that cold exposure is the primary component of isolation that induces the vocalization. We were unable, however, to suppress all ultrasound production when transferring pups to a thermoneutral (35°C) environment.

Using an infrared thermography system that allows us to estimate noninvasively heat production by brown adipose tissue, we found that pups transferred from the home nest to a 35°C test chamber exhibited sizable levels of heat production while they were vocalizing. Moreover, both heat production and ultrasound emission decreased over the 15‐min test. Next, we used extreme care to minimize thermal, and therefore respiratory, stimulation of pups before, during, and after the transfer procedure. We found that such precautions prevented both heat production and ultrasound emission following transfer. These results idicate that infant rats' thermal sensitivities are far greater than previously suspected. © 1992 Wiley & sons. Inc.
Response of bonnet macaque dyads to an acute foraging task under different motivational conditions
Authors: Andrews Michael W. , Rosenblum Leonard A.
Published: January 2005

To explore behavioral patterns in bonnet macaque mother‐infant dyads under environmental challenge, the motivation of infants to contact their mothers during a 1‐hr foraging period was manipulated in two ways. First, sessions were given in which the infants were separated from their mothers for 3 hr prior to the foraging period. Second, sessions were given in which the infants were allowed access to food prior to the foraging period, thereby presumably reducing their motivation to separate from mother to seek food for themselves during the foraging period. Neither manipulation resulted in heightened conflict within the dyads. Separation of the infants prior to the foraging period did result, in general, in mothers forfeiting foraging task engagement to attend to their infants. The extent to which a mother exhibited this pattern correlated with her level of foraging effectiveness. © 1992 Wiley & sons. Inc.
Body scale and infant grip configurations
Authors: Newell K. M. , McDonald P. V. , Baillargeon Renee
Published: January 2005

This study examined whether hand/object size ratios define common boundaries to the grip configuration patterns of infants and adults. A group of 5‐ to 8‐month‐old infants and a group of adults engaged in a displacement grasping task with inverted cups that varied in size. The findings showed that infant and adult grip configurations varied systematically with object size: More digits were brought into the contact grip configurations with increasing object size. Furthermore, when object size was scaled to hand size, common dimensionless ratios defined the grasping patterns and transitions between grasping patterns in a similar manner for both adults and infants. Consistent with a dynamical view of the development of coordination, the strong role of body scale on the developmental prehensile coordination pattern was observed for a given set of task constraints. © 1993 John Wiley & Sons, Inc.
Development of manipulation in capuchin monkeys during the first 6 months
Authors: Adams‐Curtis L. E. , Fragaszy D. M.
Published: January 2005

This study describes the orderly changes in manipulation over the first 6 months in capuchin monkeys (Cebus apella). By 6 months of age, all the basic forms of manipulation seen in adults have appeared. Actions that occur frequently in the first 8 weeks are gentle and involve sustained visual orientation and aimed reaching. Later actions are more vigorous, and involve grasping. Large increases in the rate of activity are evident over the period of development studied. The increase from the first 8 weeks to the second may be due to (a) an increase in the amount of time spent alert and active, (b) a decrease in the amount of time spent in a ventral position, (c) improvements in postural control and stamina and (d) the onset of independent locomotion. Changes in form can be attributed primarily to postural factors and to neuromuscular development (precisely aimed and controlled movements appearing in the 5th and 6th months).© 1994 John Wiley & Sons, Inc.
Cardiorespiratory functioning of preterm infants: Stability and risk associations for measures of heart rate variability and oxygen saturation
Authors: Dipietro Janet A. , Caughy Margaret O'brien , Cusson Regina , Fox Nathan A.
Published: January 2005

Cardiorespiratory measures are used with increasing frequency to assess individual differences in development in full‐term and preterm infants, yet little information exists concerning the stability of these measures or their relations to each other. This study assessed three common cardiac measures (heart period, heart period variability, and vagal tone) and two measures of arterial oxygenation based on pulse oximetry (mean pulse oxygen saturation and variability) in a sample of 35 preterm infants. Data were collected on five occasions: on 3 consecutive days in the early neonatal period, at 34 weeks postconceptional age, and at discharge. Results indicate both short‐term and longer term stability for all cardiac measures. Oxygen saturation demonstrated only short‐term stability prior to 34 weeks. Mean heart period was positively associated with both measures of heart period variability at each assessment point, while mean oxygen saturation level was inversely related to oxygen saturation variability. In addition, significant associations between cardiorespiratory patterns and perinatal risk measures were found. It is concluded that these measures reflect stable characteristics of neuroregulatory function in preterm infants.© 1994 John Wiley & Sons, Inc.
Differing perspectives of evaluation
Authors: Chelimsky Eleanor
Published: January 2005

It seems that evaluation means many things to many people. If Congress continues to mandate Federal agency evaluation with the intention of establishing agency accountability while agencies are instead sponsoring evaluation in order to improve program management, the outlook for the mutual satisfaction of both sets of users is something less than promising.
Developing an evaluation plan for Public Law 94‐142
Authors: Kennedy Mary M.
Published: January 2005

The planning process used for developing an evaluation plan can clarify the questions to be asked, suggest the appropriate methodologies to use, and increase the value and use of the evaluation findings.
Naturalistic study of evaluation utilization
Authors: Alkin Marvin C.
Published: January 2005

Despite protestations about the lack of usefulness of evaluation, evaluation utilization does indeed occur. However, its forms as well as the forces which lead to utilization are complex. In this chapter, naturalistic research is suggested as an appropriate methodology for use in the study of utilization and some findings of initial research of this type are presented.
Communication theory and the utilization of evaluation
Authors: Newman Dianna L. , Brown Robert D. , Braskamp Larry A.
Published: January 2005

The evaluation reporting process can be viewed as analogous to a persuasive communication message. As such, it is possible to study the impact of different message contents and media on different audiences.
Social program evaluation: Six models
Authors: Doctors Samuel I. , Wokutch Richard E.
Published: January 2005

Misinterpretation of evaluation results can be avoided if evaluation models are analyzed for their treatment of values and style of empirical inquiry.
Ethical issues in the use of control groups
Authors: Conner Ross F.
Published: January 2005

Is it ethical to select clients at random for a beneficial social service, then deny the benefits to a control group for the sake of science?
Training evaluators of social experiments and social programs
Authors: Lewis Joseph H.
Published: January 2005

Administering research and overseeing evaluation researchers make evident the critical role that attitudes and outlook play in comparison to sheer technical skill.
Evaluation Research Society standards for program evaluation
Authors: Anderson Scarvia B. , Braskamp Larry A. , Cohen Wallace M. , Evans John W. , Gilmore Alan , Marvin Keith E. , Shipman Virginia C. , Vanecko James J. , Wooldridge Ronald J.
Published: January 2005

This chapter contains the ERS Standards, as adopted by the ERS Council.
Stakeholder influence in the evaluation of Cities‐in‐Schools
Authors: Stake Robert E.
Published: January 2005

Deliberately involving urban education stakeholders in the Cities‐in‐Schools evaluation study was expected to increase the utility of the findings, but things did not work out that way.
Toward the future of stakeholder approaches in evaluation
Authors: Weiss Carol H.
Published: January 2005

Analysis of the assumptions that underlie the stakeholder approach suggest that some claims are cogent and others are problematical.
Six evaluation issues that synthesis can resolve better than single studies
Authors: Light Richard J.
Published: January 2005

Syntheses of research studies identify important interactions that any one study rarely finds.
Randomized experiments in the federal courts
Authors: Lind E. Allan
Published: January 2005

This is an overview of recent experiments in the courts, and the factors that should be taken into account in conducting randomized tests in this setting.
Random assignment of chronically mentally ill. persons to hospital or community treatment
Authors: Test Mary Ann , Burke Suzanne Senn
Published: January 2005

This chapter discusses a series of experimental tests of alternative approaches to treating the chronically and potentially chronically ill.
The teaching of evaluation in health settings: University of Michigan
Authors: Wortman Paul M. , Yeaton William H.
Published: January 2005

This chapter views courses in evaluation research as integral parts of advanced degree training in public health. Three such courses are discussed.
Validity typologies and the logic and practice of quasi‐experimentation
Authors: Mark Melvin M.
Published: January 2005

Validity typologies can enhance our understanding of quasi‐experiments, but they can also serve as blinders. We can go beyond the primary concerns of validity typologies by studying causal process and by being explicit about the reasoning that underlies our inferences.
The politics of program evaluation
Authors: Chelimsky Eleanor
Published: January 2005

Evaluation must take into account both executive and legislative politics and their interactions. This implies an evaluation process that can be represented as a five‐part continuum, and requires numerous departures from past thinking about evaluation. The evaluator must assume a major share of the responsibility for translating policy questions into knowledge that is credible, timely, responsive, and usable.
Using evaluation in controversial settings: The client's perspective
Authors: Rogers Joy J.
Published: January 2005

Clients value the stabilizing force that evaluation can bring to settings troubled by conflicting value perspectives.
Federal evaluation in a legislative environment: Producing on a faster track
Authors: Chelimsky Eleanor
Published: January 2005

Evaluations must respond rapidly to legislative information needs. In certain cases, this implies the development of methods that can provide answers even more quickly than usual. Currently, GAO is testing three such methods: the evaluation synthesis, the use of extant data, and the evaluation planning review. All three methods rely heavily on past research, all place heavy time pressures on evaluators, and all are highly promising in terms of user satisfaction.
Getting the system to respond to evaluation findings
Authors: Mowbray Carol T.
Published: January 2005

Just as we expend effort to acquire resources to design and conduct effective evaluations, so should our energies be directed at ensuring that evaluations will be used. Suggestions for enhancing the use of evaluation studies are the major focus of this chapter.
Integrating evaluation into a program for increased utility and cost‐effectiveness
Authors: Patton Michael Quinn
Published: January 2005

The most useful and possibly the cheapest form of evaluation would yield results coinciding with ongoing management procedures. While this kind of evaluation may never be fully realized, it is possible to provide a continuous stream of evaluative data and analysis by introducing evaluation into project management at its inception. This chapter outlines such an approach.
Assessing social‐psychological classroom environments in program evaluation
Authors: Haertel Geneva D. , Walberg Herbert J.
Published: January 2005

Reliable, valid, and efficient paper‐and‐pencil measures of the social learning environment in classrooms are increasingly prominent in evaluations as both predictors and program outcomes.
Evaluation and the political appointee
Authors: Carlson Ronald H.
Published: January 2005

To meet the needs of politically appointed program managers, evaluators need to overcome organizational and evaluation‐related barriers.
Process dimensions in program evaluation
Authors: Oman Ray C.
Published: January 2005

This chapter presents a framework for examining the process dimensions of evaluation, arraying functional steps against several perspectives.
Evaluator as power broker: Issues in the Maghreb
Authors: Thompson Randal Joy
Published: January 2005

In certain milieus, outside foreign evaluators function most effectively behind the scenes by discerning critical stakeholder issues, assuming responsibility for the issues, and negotiating to get them formally accepted as the focus of the evaluation.
Evaluation and business issues: Tools for management decision making
Authors: Brandenburg Dale C.
Published: January 2005

Linking business issues and decision making to training evaluation activities determines the overall success of training efforts.
AIDS prevention: A public health psychology perspective
Authors: Rugg Deborah L.
Published: January 2005

To prevent HIV infection we must influence risky sexual and drug‐using practices, some of the most basic yet complex of human behaviors. No single discipline or one‐shot intervention is going to solve this problem; rather, a sustained, multidimensional, interdisciplinary effort with repeat exposures to a variety of well‐planned and targeted strategies is essential.
Using program theory to describe and measure program quality
Authors: Bickman Leonard , Peterson Keith A.
Published: January 2005

Measures of program quality can be derived using component program theory and consensus building with panels of experts.
A pattern‐matching approach to link program theory and evaluation data
Authors: Marquart Jules M.
Published: January 2005

A pattern‐matching approach provides a useful framework for developing and testing program theory.
Centralized versus decentralized coordination in the adult day health care evaluation study
Authors: Hedrick Susan C. , Sullivan Jean H. , Ehreth Jenifer L. , Rothman Margaret L. , Connis Richard T. , Erdly William W.
Published: January 2005

Decisions about the appropriate balance between centralized and decentralized staffing and responsibilities in multisite evaluations should be based on scientific, administrative, and political considerations.
Multisite evaluations of health care policies and programs
Authors: Freedman Jay A.
Published: January 2005

The health care arena has a number of unique features that generally facilitate and influence the conduct of multisite evaluations.
Using financial incentives to manage the solid waste stream
Authors: Spindler Charles J.
Published: January 2005

States can manage the solid waste stream in part by using financial incentives that encourage the beverage industry to undertake voluntary recycling programs. Two approaches, in particular, represent innovations in public‐private partnerships, or privatization: preemptive partnerships and compelled partnerships.
Analysis of investigative features of select evaluation studies
Authors: Fournier Deborah M.
Published: January 2005

Analysis of the nature and variations of investigative characteristics can shed new light on the improvement of evaluation theory and practice.
“I prayed real hard, so I know I'll get in”: Living with randomization
Authors: Lam Julie A. , Hartwell Stephanie Wilson , Jekel James F.
Published: January 2005

Some of the practical difficulties encountered when using an experimental design involving human subjects with multiple serious needs are outlined. Suggestions are given for dealing effectively with these difficulties, and the chapter provides further critical commentary.
Effects of randomization on a homeless services initiative: A comment
Authors: Johnston Paul , Swift Patrick
Published: January 2005

The use of experimental methods in a homeless service initiative confronted a variety of problems not reported by Lam, Jekel, and Hartwell. These include ethical and internal validity issues, organizational problems, effects on the research team itself, and the impact of research as a requirement for services on New Haven's public institutions.
What constitutes misuse?
Authors: Stevens Carla J. , Dial Micah
Published: January 2005

This introductory chapter offers a discussion of evaluation misuse, including ways in which evaluations and their results may be misused, by whom, and for what reasons.
Using cluster evaluation in the context of science education reform
Authors: Jenness Mark , Barley Zoe A.
Published: January 2005

Cluster evaluation is a collaborative method for evaluating the impact of a set of projects with similar goals and objectives. As the evaluation is constructed out of the shared visions, values, and directions of the cluster of projects, new roles and relationships for evaluators emerge.
Nervenkitt: Notes on the history of the concept of neuroglia
Authors: Somjen George G.
Published: January 2005

The evolution of concepts concerning the identity and the functions of neuroglia is traced. Some of the main ideas in the works of Virchow, Deiters, Golgi, Lenhossék, Lugaro, Ramón y Cajal, del Río‐Hortega, Achúcarro, Penfield, and others are highlighted.
Effect of benzodiazepines and pentobarbital on the GABA‐induced depolarization in cultured astrocytes
Authors: Backus Kurt Harald , Kettenmann Helmut , Schachner Melitta
Published: January 2005

We have previously shown that cultured astrocytes from neonatal rat cerebral cortex are depolarized by GABA. The underlying ionic mechanism, activation of a Cl−− conductance and responses to an agonist and antagonists were found to be similar to those of the neuronal GABAA receptor (Kettenmann et al.: Brain Research 404:1–9, 1987; Kettenmann and Schachner: Journal of Neuroscience 5:3295–3301, 1985). To characterize further the pharmacological properties of the GABA receptor we have tested the influence of pentobarbital and benzodiazepines on the GABA response. Pentobarbital potentiated and prolonged the GABA‐induced depolarization and enhanced the velocity of the depolarization. Agonists of the neuronal benzodiazepine receptor, flunitrazepam, diazepam, and midazolam, increased the GABA‐induced depolarization. As in neurons, an antagonist of the benzodiazepine receptor, Ro 15‐1788, blocked the flunitrazepam‐induced enhancement of the GABA response. In contrast to their effects on neurons, the inverse agonists Ro 22‐7497 and DMCM increased the GABA‐induced depolarization. The ligand of the putative peripheral benzodiazepine binding site, Ro 5‐4864, did not show consistent effects on the GABA response.

These studies confirm that cultured astrocytes express GABAA receptors. This receptor is similar to the neuronal GABAA receptor with regard to Cl−− conductance and its pharmacological responses to muscimol, bicuculline, picrotoxin, pentobarbital, and benzodiazepine agonists and an antagonist, but it is different in its responses to inverse agonists of the benzodiazepine site. The physiological role of the glial GABAA receptor is at present unknown.
Plasma membrane of cultured oligodendrocytes: III. Relatedness to myelin
Authors: Szuchet Sara , Polak Paul E. , Yim Sung Hye , Arvanitis Dimitrios
Published: January 2005

We have compared highly purified fractions of oligodendrocyte plasma membrane to myelin by one‐ and two dimensional gel electrophoresis and found them to be distinct. The major myelin proteins—proteolipid protein (PLP), DM‐20, and myelin basic protein (MBP), which dominate the sodium dodecyl sulfate polyacrylamide gel electrophoresis pattern of myelin–were minor components of the plasmalemma. However, 2′,3′, cyclic nucleotide phosphodiesterase (CNPase) and myelin‐associated glycoprotein (MAG) were represented equally in both membranes. Labeling the cells with various precursors followed by isolation of plasmalemma revealed that newly synthesized PLP, DM‐20, CNPase, and MAG were incorporated into the plasma membrane of “floating” oligodendrocytes (i.e., nonattached to substratum). This was not so with MBP. Nevertheless, scattered patches of MBP were localized on the plasma membrane of intact cells using the immunogold method at the electron microscopic level. The data are consistent with the notion that MBP is not a constituent of the plasma membrane of mature oligodendrocytes (the MBP patches on intact cells are likely remnants from past association with myelin) but is rapidly associated with the plasmalemma of myelinating oligodendrocytes (i.e., attached cells). It is suggested that phosphorylation of MBP provides the triggering signal for plasma membrane association. In order to analyze the minor proteins in myelin and compare them to the plasma membrane by two‐dimensional gel electrophoresis, myelin was extracted with chloroform:methanol to remove PLP, DM‐20, and MBP. Even in the absence of PLP, DM‐20, and MBP the pattern of extracted myelin still differed from that of plasmalemma indicating that their minor protein compositions were not the same. Myelin was characterized by a group of proteins that clustered at pI 5.5–6.5 and Mr 40,000–60,000 of which α‐tubulins, β‐tubulins, and actin are part: the plasmalemma had tubulins and actin but in different proportions. Our findings indicate that in addition to PLP, DM‐20, and MPB, myelin is also enriched relative to the plasmalemma in another group of proteins.
Astrocytes as eicosanoid‐producing cells
Authors: Murphy Sean , Pearce Brian , Jeremy James , Dandona Paresh
Published: January 2005

A variety of prostaglandins and leukotrienes, together with thromboxane and prostacyclin metabolites, can be detected in central nervous tissues and in cerebrospinal fluid. Defined cultures of astrocytes have revealed these cells to be a major source of eicosanoids. In common with other eicosanoid‐producing cells, agents such as calcium ionophores and phorbol esters are potent stimuli for promoting release. While in other tissues agonists for receptors linked to calcium mobilisation prompt eicosanoid release, this does not seem to be the case in astrocytes, though a range of such receptors are present. The notable exceptions to this observation are adenosine triphosphate and adenosine diphosphate, presumably acting through P2 purinergic receptors. Many cell types in the CNS are targets for eicosanoids, possessing receptors linked to adenylate cyclase or phospholipase C. An appreciation of the functional significance of activation of these receptors in just now begining. Eicosanoids have effects in the CNS that involve not only the vascular supply but also synaptic modulation and immune regulation.
Electrogenic Na+/HCO3−cotransport in neuroglia
Authors: Astion Michael L. , Orkand Richard K.
Published: January 2005

Membrane potential recording from glial cells in Necturus optic nerve in the presence of 2 mM Ba++, which was added to block the K+ conductance, gave the following results. (1) In HCO3−‐free, low‐Na+ solutions (11% of control; Na+ replaced with N‐methyl‐D‐glucamine), the hyperpolarizing effect of adding 10 mM HCO3− was reduced by approximately 80%.(2) 4‐acetamido‐4′‐isothiocynato‐stilbene‐2,2′‐disulfonic acid (SITS, 0.1 or 1 mM) reduced the effect of HCO3− by at least 50%.(3) In the presence of HCO3−, reduction of Na+ caused a depolarization which was much larger than that observed in nominally HCO3−‐free solutions. These observations indicate the presence in the glial membrane of an electrogenic Na+/HCO3− contransporter in which the stoichiometry of HCO3− to Na+ is greater than 1.
Pure astrocyte cultures derived from cells isolated from mature brain
Authors: Norton William T. , Farooq Muhammad , Chiu Fung‐Chow , Bottenstein Jane E.
Published: January 2005

Enriched preparations of oligodendrocytes, isolated either from adult bovine brain or from 30‐day‐old rat brain, eventually yield cultures in MEM‐15% calf serum that contain, in addition to oligodendrocytes, proliferating astrocytes and variable numbers of fibroblast‐like cells. If these cultures are switched to a serum‐free defined medium during the 1st week, mixed cultures containing only oligodendrocytes and astrocytes are obtained. Bovine cultures can be replated and purified by selective adhesion to yield cultures that are < 99% astrocytes; similar procedures were not successful with rat cultures. Cytoskeletal preparations of the purified astrocyte cultures from mature bovine brain contain both vimentin and glial fibrillary acidic protein (GFAP), but vimentin is by far the major intermediate filament protein. Thus, the intermediate filament composition of these astrocytes is similar to that of astrocytes in primary cultures obtained from neonatal rat brain. Immunofluorescent studies of these cultures at 24 hr in vitro show that there are no GFAP+ cells in cultures of either species; the bovine cultures contain < 95% GC+ cells; and the rat cultures contain 90% GC+ cells. After a few days in vitro flat cells appear that are vimentin+/GFAP–/GC–. In serum‐free medium these cells eventually become vimentin+/GFAP+. We propose that the astrocytes that grow in these cultures arise from a population of glial precursor cells, which are present even in adult brain and are isolated together with oligodendroglia, and that they do not derive from contaminating mature astrocytes. Thus, the astrocytes in our cultures may have the same origin as astrocytes grown in culture from dissociated neonatal brain.
Size and density of glial and neuronal cells within the cerebral neocortex of various insectivorian species
Authors: Stolzenburg Jens‐Uwe , Reichenbach Andreas , Neumann Michael
Published: January 2005

Morphometric measurements were done on frontal sections through the somatosensory neocortex of various insectivorian species. All measured parameters varied with the size of animals; there was a better correlation with the ventriculartopial brain wall thickness than with the brain weight. The following rules were evaluated: with increasing brain wall thickness, (1) lamina I becomes thinner; (2) the nuclei of both neuronal and glial cells become larger; (3) the volume density of neuronal cells decreases greatly; (4) the volume density of glial cells increases slightly; and (5) as a result, the glia:neuron index increases markedly. There was no equal number of neurons under a unit surface area in the cortices of any species studied. Developmental processes that might account for the above‐mentioned rules are discussed in this report.
Activation of polyphosphoinositide metabolism as a signal‐transducing system coupled to excitatory amino acid receptors in astroglial cells
Authors: Milani Daria , Facci Laura , Guidolin Diego , Leon Alberta , Skaper Stephen D.
Published: January 2005

Excitatory amino acids (EAA) are known to induce an increase in the breakdown of polyphosphoinositides (PI) in brain slices and in dispersed cultures of neurons. We have now used astroglia cultured from newborn rat cerebra to demonstrate that glutamate provokes, in [3H]inositol‐labeled cells, an accumulation of inositol phosphates in a time‐ and concentration‐dependent manner. The ED50 value for glutamate was 40 μM. Quisqualate, ibotenate, and kainate were also active, with their relative potencies in the order of quisqualate > ibotenate >> kainate. No effect was detected with N‐methyl‐D‐aspartate and quinolinic acid in the absence of Mg2+. The nonselective glutamate receptor antagonist γ‐D‐glutamylglycine fully inhibited glutamate agonist‐induced PI breakdown. A brief pretreatment of the astroglial cells with phorbol esters negated these effects of EAA receptor agonists, suggesting a feedback role for protein kinase C in phospholipase C action. Glutamate also elevated cytosolic free Ca2+ in Fura‐2‐loaded astroglial cells, as assessed by digital fluorescence imaging microscopy. Since a close metabolic partnership is known to exist between neurons and glia, these findings may have important functional consequences for neural cells in vivo.
Increase in glial intracellular K+ in drone retina caused by photostimulation but not mediated by an increase in extracellular K+
Authors: Coles Jonathan A. , Schneider‐Picard Gisela
Published: January 2005

The predominant glial cells of the drone retina (outer pigment cells) respond to an increase in extracellular [K+] (K0) by a net uptake of K+; thus, they contribute to bringing K0 back toward its baseline value. The authors report herein that there is also a different mechanism by which light stimulation of the retina causes an increase in intracellular free [K+] in the glial cells. In superfused retinal slices, after 5–10 minutes of continuous illumination at physiological intensities, extracellular [K+] often fell back to below its original level in the dark. This fall can be explained by increased activity of the Na/K pump in the photoreceptors and diffusion of K+ down their axons. Despite the absence of raised K0, K+‐selective microelectrodes in glial cells recorded a small increase in intracellular [K+] that was maintained for the duration of the illumination; i.e. A change occurred in the glia that was not mediated by an increase in K0. The increase in intracellular [K+] is not mediated by illumination of the screening pigment in the glia. Unless the increase is caused by illumination of some other, unknown, pigment in the glia, the results show that some unidentified signal (that is not K+) passes from the photoreceptors to the glia.
Inhibition of peroxisomal beta‐oxidation and brain development in rats
Authors: Van Den Branden Christiane , Dacremont Georges , Hooghe Robert , Roels Frank
Published: January 2005

Thioridazine, an inhibitor of peroxisomal beta‐oxidation, was administered orally to nursing rats during the period of maximal myelination in the pups (8–21 days postnatally). Under the experimental conditions, thioridazine causes accumulation of C24 and C26 fatty acids in pup brain lipids, an effect we consider to be a typical consequence of inhibited peroxisomal beta‐oxidation. In the corpus callosum of treated pups, the relationship between axon diameter and myelin sheath thickness is altered compared with matched controls. Thioridazine also induces undernourishment effects in 21 day‐old rats. Body and brain weight are severely reduced. Liver peroxisomes show a starvation‐type metabolism. Undernourishment is known to influence myelination in developing rat brain. However, known consequences of undernourishment, such as decreased myelin concentration in whole brain, decreased percentage of myelinated fibers, and decreased granule‐to‐Purkinje cell ratio are not present.
Orthogonal arrays of particles in plasma membranes of Müller cells in the guinea pig retina
Authors: Gotow Takahiro , Hashimoto Paulo H.
Published: January 2005

Plasma membranes of guinea pig Müller cells were examined with a freeze‐fracture technique to see how orthogonal arrays are distributed in the avascular retina. Examination of the portion approximately intermediate between the optic disc and equator of the eyeball showed that all end‐feet of Müller cells were provided with arrays. Orthogonal arrays were concentrated on vitreal end‐foot membranes, i.e., membranes that were covered by the basal lamina and contacted the vitreous body, called vitreal membranes here. The arrays were rarely observed in the portions of end‐feet that did not contact the vitreous body, called lateral membranes. The distribution density of arrays in the vitreal membranes was 122.5 ± 45.3/μm2, which was over 10 times higher than that (9.6 ± 9.6/μm2) in the lateral membranes. The arrays became numerous and extended in shape at the periphery of the vitreal membrane, characteristically aligned in rows at the border where vitreal met lateral membrane, but never intruded into the domain of lateral membrane. Some arrays were composed of loosely attached particles and/or rod‐like profiles. Sometimes rod‐like profiles, 9–13 nm wide and 20–50 nm long, called linear structures here, were isolated, and sometimes they appeared in rows. Ordinary intramembrane particles (IMPs) were significantly smaller and less numerous in vitreal than in lateral membranes. IMPs larger than 9 nm in diameter were significantly fewer in the vitreal membranes, which suggests that they have been consumed to form the arrays. Although the distribution of orthogonal arrays is similar to that of K+ channels (Newman: J. Neurosci., 7:2423–2432, 1987), we consider the array an unlikely candidate for the ion channel, because its subunit particles do not protrude onto either the inner or outer surface of the membrane (Gotow and Hashimoto: J. Neurocytol., 17:399–413, 1988). Judging from their unique alignment in rows where the membrane is bent and vitreal and lateral membranes meet, the arrays may contribute to some membrane stability, resisting the physical tension at the interface with mesenchymal tissue.
Müller (glial) cells but not astrocytes in the retina of the goldfish possess orthogonal arrays of particles
Authors: der Emde Karin Berg‐Von , Wolburg Hartwig
Published: January 2005

Müller cells as the main glial component of the retina were investigated in the goldfish by means of ultrathin sections and freeze‐fracture replicas. In the optic nerve head, they were directly compared with astrocytes. Whereas astrocytic endfeet bordering the vitreous body can easily be identified by their dense bundles of intermediate filaments, scarce membranous organelles, paravitreous caveolae, and lateral desmosomes, Müller cell endfeet reveal a looser arrangement of intermediate filaments, a characteristic pattern of triangularly shaped endoplasmic reticulum, large and pale mitochondria, and, if at all, very few desmosome‐like junctions. The paravitreous membranes at the cytoplasmic face are covered by a fuzzy coat, which is less marked in astrocytic endfeet. Caveolae are lacking. Considering the freeze‐fracture architecture of the membranes of both glial cell types, the Müller cells reveal orthogonal arrays of particles (OAP), which were predominantly located opposite to the inner limiting membrane; their density (109 ± 33 OAP/μm2) decreases abruptly with the loss of the contact between membrane and vitreous body. In contrast, astrocytes of the optic nerve head in the retina do not show any OAP in their membranes at all and are interconnected by tight junctions and desmosomes. The hypothesis suggesting that OAP might be correlated with K+ channels involved in the spatial buffering of the extracellular space is reconsidered with comparative reference to recent electrophysiological data. Further, the heterogeneity of Müller cell and astrocyte membrane equipment with OAP in the goldfish is briefly discussed.
Glutamine synthetase modulation in astrocyte cultures of different mouse brain areas
Authors: Khelil M. , Rolland B. , Fages C. , Tardy M.
Published: January 2005

Astroglial cells from mouse cerebral hemispheres, cerebellum, olfactory bulbs, and medulla oblongata were grown in the presence of either hormones (hydrocortisone, insulin) or cell second messengers (dBcAMP, dBcGMP). Glutamine synthetase (GS) specific activity, GS protein level, and GS translation were investigated under the effect of these factors. Hydrocortisone produced a simultaneous increase in GS translation, GS level, and activity. This increase was observed in the astrocytes cultured from the four brain areas but at a variable magnitude depending on the area. The hydrocortisone effect appeared at the transcriptional level. Inversely, insulin decreased both the GS activity and the in vitro translated GS. This effect was seen only in the olfactory bulbs and the medulla. DBcAMP increased the GS biological activity only in the cerebral hemisphere cultures. It raised, however, the level of translated GS and GS protein in astrocytes from all the areas, suggesting a post‐translational effect for intracellular cAMP. DBcGMP only affected GS in the astrocytes from cerebral hemispheres and the medulla modulating either the GS transcription or the messenger RNA stability.

These results suggest specific regulation for GS expression, depending on the brain area from which the cells were dissociated or on the astroglial cell population present in these cultures affecting either the transcription, the mRNA stability, or the biological activity of the protein.
Myelination requirements of central nervous system glia in vitro: Statistical validation of differences between glia from adult and immature mice
Authors: Stanhope Gail B. , Billings‐Gagliardi Susan , Wolf Merrill K.
Published: January 2005

Gila from adult optic nerve, like those from immature nerve, have been shown to colonize and myelinate cerebellar axons in combined cultures. Preliminary experiments suggested, however, that the glia from adults might require the added nutrients and/or chemical signals present in a serum and embryo extract containing medium to produce myelin, whereas glia from immature animals could form myelin in a chemically defined medium described by Hendelman et al. (1985). This observation demanded rigorous confirmation, since it depended on the meaning of a negative result (the absence of myelin), which could produced by many factors other than the composition of the medium in this complex culture system. Here we report an extensive series of experiments, with controls for all other factors, that provide unquestonable statistical validation of the additional myelination requirements of the glia from adult nerves. The cultures can now be used to identify these required substances, which may be limiting factors for central nervous system myelin regeneration in situ.
Proliferation and differentiation of a transfected schwann cell line is altered by an artificial basement membrane
Authors: Yoshino Jun E. , Neuberger Timothy J. , Cornbrooks Carson J. , Tennekoon Gihan I. , Eng Larry F. , Devries George H.
Published: January 2005

Rapidly dividing transfected Schwann cells were grown on MatrigelTM, a reconstituted basement membrane gel. Matrigel decreased the proliferation of the cells by 75% when compared to sister cultures that were grown on an untreated plastic substrate. Some transfected cells plated onto a Matrigel substrate formed colonies similar to that observed when the cells were plated on a plastic substrate. Additionally, many cells on Matrigel assembled themselves into fascicles projecting away from the colonies. These fascicles were composed of transfected Schwann cells that had assumed a bipolar appearance reminiscent of quiescent secondary Schwann cells in culture. Transfected cells grown on Matrigel contained approximately 10‐fold less glial fibrillary acidic protein when compared to sister cultures grown on an untreated plastic substrate. By indirect immunofluorescence laminin immunoreactivity appeared as globules within the cytoplasm of the cells which were cultured on a plastic substrate. However, cells that were grown on the Matrigel substrate appear to organize laminin in a linear array around themselves. These results demonstrate that the presence of an artificial basement membrane alters the morphology, rate of proliferation, and state of differentiation of a transfected Schwann cell line.
The excitatory neurotransmitter glutamate causes filopodia formation in cultured hippocampal astrocytes
Authors: Cornell‐Bell Ann H. , Thomas Prem G. , Smith Stephen J.
Published: January 2005

Can neurons induce surrounding glia to provide a more favorable microenvironment? Synapses and nerve growth cones have been shown to release neurotransmitters (Hume et al. Nature 1983;305:632–634; Kater et al. Trends Neurosci. 1988;11:315–321; Young and Poo Nature 1983;305:634–637) providing a possible mechanism for this type of control. The excitatory neurotransmitter glutamate induces an increase in the number of filopodia on the surface of astrocytes cultured from the neonatal rat hippocampus. This seems to be associated with a receptor‐mediated event that is activated to a lesser degree by the quisqualate and kainate, but not NMDA receptors. In addition, time‐lapse video recordings have revealed a rapid extension of filopodia from the apical margins of cells treated with glutamate. The apical margins of glutamate‐treated cells studied with electron microscopy contained dense cortical actin networks that are devoid of microtubules. Coated pits are often seen to invaginate from the the apical membrane in the vicinity of filopodia. A receptor‐binding step may be followed by a rapid reorganization of cortical actin resulting in actin‐containing filopodia. This process may be mediated by inositol lipid hydrolysis. Pyramidal neurons settled on glial cultures induced filopodia to form around the entire margin of growth cones and neurite tips suggesting that these events might occur in situ.
Astrocytic reactions in spinal gray matter following sciatic axotomy
Authors: Gilmore Shirley Ann , Sims Terry J. , Leiting Jane E.
Published: January 2005

Astrocytic responses following unilateral sciatic nerve axotomy were examined in the spinal gray matter. Using an antiserum to glial fibrillary acidic protein (GFAP), immunoreactive astrocytes were studied in both dorsal and ventral gray matter at intervals from 2 days through 34 days post‐axotomy. In all axotomized animals, increased numbers of strongly immunoreactive astrocytes were present in the gray matter ipsilateral to the surgery. Such astrocytes were absent from the contralateral intact side and from gray matter bilaterally in adjacent spinal segments not involved in formation of the sciatic nerve. These GFAP‐positive astrocytes occurred not only in association with large motor neurons in the ventral gray matter but also in association with central processes of dorsal root ganglion neurons in the dorsal gray matter. The response was quite rapid, being discernible both dorsally and ventrally as early as the second post‐operative day. This increased GFAP immunoreactivity persisted throughout the entire observation period, with the perikarya of large ventral motor neurons appearing to become surrounded or encapsulated by the immunoreactive processes. A further alteration noted at the longest post‐operative intervals was the presence in the ventral gray matter of astrocytes appearing to be binucleate. The data obtained indicate that the astrocytic response is not related solely to reactions in motor neurons and, furthermore, the rapidity with which it develops in the dorsal gray matter suggests that its induction is not dependent upon transganglionic degeneration, which others have reported to occur weeks after peripheral nerve injury.
Substance P modulation of the membrane potential of the Schwann cell of the squid giant nerve fibre
Authors: Evans Peter D. , Reale Vincenzina , Merzon Rosa Maria , Villegas Jorge
Published: January 2005

Substance P produced a dose‐dependent, logn‐lasting hyperpolarization of the membrane of the Schwann cells of the giant nerve fibre of the tropical squid. A survey of the effectiveness of a range of other naturally occurring tachykinin agonists suggested that the receptors present on the squid Schwann cell belong to the subtype SP‐P or NK1, for which substance P is the preferred agonist. A survey of the effectiveness of a range of substance P fragments indicated that the direct hyperpolarizing effects of the substance P molecule were mediated by peptides with an intact amidated C‐terminal. However, a second subset of receptors that can be activated by N‐terminal fragments and analogues lacking an amidated C‐terminal was also present in this preparation. The non‐subtype‐specific antagonist D‐Arg1, D‐Trp7,9, Leu11 substance P (spantide) was a potent blocker of the effects of substance P in this preparation. Activation of the substance P receptors did not interact with the effects induced by activation of either the nicotinic cholinergic receptors or octopaminergic receptors present in this preparation. However, it did potentiate the effects of activation of the receptors for vasoactive intenstinal peptide (VIP), either in response to bath application of the peptide or due to their activation by the release of an endogenous VIP‐like peptide after stimulation of the giant axon.