bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dopaminergic and gabaergic interneurons of the olfactory bulb are derived from the neonatal subventricular zone
Authors: Betarbet Ranjita , Zigova Tanja , Bakay Roy A.E. , Luskin Marla B. 
Published: July 2002

AbstractEarlier studies in our laboratory have demonstrated that a discrete region of the anterior part of the neonatal subventricular zone (SVZa) contains exclusively neuronal progenitor cells. The descendants of the SVZa progenitor cells are destined for the granule cell and glomerular layers of the olfactory bulb, where they differentiate into granule and periglomerular cells, the interneurons of the olfactory bulb, respectively. In the present set of experiments we examined the neurotransmitter phenotype of the SVZa‐derived cells. In order to label SVZa‐derived cells, the cell proliferation marker bromodeoxyuridine (BrdU) was injected into the SVZa of postnatal day 2 (P2) rats. After 3 weeks, by which time most of the SVZ‐aderived cells have migrated to their final destination in the bulb, the animals were perfused and their brains processed for immunohistochemistry. To identify the neurotransmitter phenotype of the SVZa‐derived cells, sagittal sections of the forebrain, including the olfactory bulb, were double‐labeled with an antibody to BrdU in conjunction with an antibody to γ‐amino‐butyric acid (GABA) or tyrosine hydroxylase (TH), the rate limiting enzyme in the synthesis of dopamine. Using simultaneous indirect immunofluorescence to detect the presence of single‐ and double‐labeled cells, we found that 59% and 51% of the BrdU‐positive cells were immunoreactive for GABA in the granule cell and glomerular layers, respectively. In addition, 10% of the BrdU‐positive periglomerular cells were immunoreactive for TH. The presence of double‐labeled (BrdU‐positive/GABA‐positive and BrdU‐positive/TH‐positive) cells in the olfactory bulb, demonstrates that the SVZa is a source of the GABAergic and dopaminergic interneurons of the olfactory bulb during postnatal development.
Muscarinic and purinergic Ca2+ mobilizations in the neural retina of early embryonic chick
Authors: Sakaki Yoko , Fukuda Yutaka , Yamashita Masayuki 
Published: July 2002

AbstractAcetylcholine and adenosine triphosphate (ATP) raise intracellular Ca2+ concentration via muscarinic receptors and P2U purinoceptors by releasing Ca2+ from intracellular Ca2+ stores in the neural retina of early embryonic chick. The signal transduction mechanisms for the muscarinic and purinergic Ca2+ responses with fura‐2 fluorescence measurements were studied. Li+ (1 mM), which inhibits phosphatidylinositol metabolism, enhanced both the Ca2+ rises to carbamylcholine (CCh, 30 μM), a muscarinic agonist, and ATP (200 μM). Thapsigargin (250 nM), an inhibitor of Ca2+‐ATPase of inositol trisphosphate (IP3)‐sensitive Ca2+ stores, abolished both the Ca2+ rises to CCh (100 μM) and ATP (500 μM). U‐73122 (2 μM), an inhibitor of phospholipase Cb, suppressed the Ca2+ rise to ATP (500 μM), but its analog U‐73343 (2 μM) did not suppress it. In contrast, both U‐73122 and U‐73343 suppressed the Ca2+ rise to CCh (100 μM). Pertussis toxin (250 ng/ml) suppressed the ATP‐induced Ca2+ rise at least partly, whereas no inhibition was observed on the CCh‐induced Ca2+ rise. Cross‐talk occurred between the muscarinic and purinergic Ca2+ mobilizations but they were not occlusive. This study suggests that the muscarinic and purinergic Ca2+ mobilizations utilize IP3‐sensitive Ca2+ stores, but different signal transduction pathways are involved in between the muscarinic and purinergic Ca2+ responses.
Effect of experimental hyperphenylalaninemia on the postnatal rat brain
Authors: Ushakova Alina A. , Gubkina Helena A. , Kachur Victoria A. , Lepekhin Eugene A. 
Published: July 2002

AbstractThe molecular mechanism of the disturbance to brain development caused by phenylketonuria remains mostly unknown. We have studied three molecular markers that reflect the development of neurons, glia and the extracellular matrix of the postnatal rat brain in an animal model of hyperphenylalaninemia, in order to elucidate the possible mechanism by which increased phenylalanine influences brain development. The contents of NCAM, GFAP and hyaluronate‐binding activity were compared in cerebellum and telencephalon of normal rats and those subjected to high phenylalanine. No statistically significant changeswere found in telencephalon when experimental animals were compared to controls. In the hyperphenylalaninemic cerebellum, the developmental dynamic of NCAM content (represented by two peaks at about postnatal days 5 and 22 during normal development) is dramatically altered. The GFAP content in the cerebellum of treated rats exceeded those in controls significantly during late developmental stages (postnatal days 28–35). Hyaluronate‐binding activity in the extracellular protein fraction from treated rat cerebellum was increased compared to normal rat at the early stages of development only (postnatal day 7). These results suggest that high serum phenylalanine may lead to permanent brain dysfunction through a disturbance of a wide range of developmental events.
Morphological evidence for supporting cell to hair cell conversion in the mammalian utricular macula
Authors: Li Lin , Forge Andrew 
Published: July 2002

AbstractThe possible origin of the immature hair cells that appear in the utricular maculae of guinea pigs following gentamicin‐induced hair cell death was investigated. Guinea pigs were continuously infused with bromodeoxyuridine, to label proliferating cells and their progeny, for 2 weeks after inducing damage to the inner ear on one side with gentamicin. The opposite ear in each animal served as control. Serial sections were cut through the entire utricular maculae of both ears of each animal and the number of labelled cells in the epithelium and underlying connective tissue was counted. Label was present in cells in the sensory epithelium in the utricles from the drug exposed ears but not in the controls. The nuclei of cells in the underlying connective tissue were also labelled in both ears. Some of the labelled nuclei in the epithelium were at the level normally occupied by hair cells, but most were at the level of supporting cell nuclei. However, the total number of labelled nuclei in the sensory epithelium was small; the maximum was 12 in one animal. The number of labelled nuclei in the connective tissue of the treated ears was significantly greater than the number in the untreated ear. This confirms that cell proliferation is stimulated in the mature mammalian utricular macula after hair cell loss, but the extent to which it occurs appears to be insufficient to explain the recovery in hair cell numbers which is observed. Detailed thin section studies of the utricular maculae of gentamicin‐treated animals over a prolonged post‐treatment period were also performed. In utricles which had suffered damage, there were cells which, like supporting cells but unlike hair cells, were resting on basement membrane, but which possessed at their apical ends organized bundles of microvilli similar to immature hair cell stereocilia. Other cells with more obvious stereocilia remained in contact with the basement membrane via and a small foot process. In still other cells, where a stereociliary bundle was obvious and almost mature in appearance, there was a foot process extending towards the basement membrane but not quite in contact, suggesting it had just detached. All these cells were contacted by nerve endings and specialization of the membranes were apparent at the site of cell‐neurone contact. The morphological characteristics of these cells are consistent with phenotypic conversion of supporting cells into hair cells and this may account for some of the hair cell production in the mature mammalian vestibular sensory epithelia after hair cell death.
Viral‐mediated gene transfer in the cochlea
Authors: Weiss Melissa A. , Frisancho Juan C. , Roessler Blake J. , Raphael Yehoash 
Published: July 2002

AbstractGene transfer is an exciting new tool in medical therapy and scientific investigation, but only very recently has it begun to be developed in the auditory system. This paper describes in vivo and ex vivo experiments using an adenoviral vector (Ad. RSVntlacZ), which is a replication‐deficient virus based on a human adenoviral (serotype 5) genomic backbone. The in vivo experiments demonstrate successful gene transfer into multiple types of cochlear cells. We observed a relatively efficient transduction, several weeks of sustained transgene expression and an absence of major lethal cytotoxicity in spiral ganglion and epithelial cells of the cochlea in adult animals. The ex vivo experiments were performed using fibroblasts transduced in vitro with Ad. RSVntlacZ. Two weeks after inoculation of the fibroblasts into the perilymph, we observed transplanted fibroblasts, which were adherent to the lining of the perilymphatic spaces, and were expressing the lacZ transgene. We speculate that, as the genetic basis of degenerative cochlear diseases is characterized on a mutational level, transgene expression will allow us to test hypotheses regarding the effects of specific genes on cochlear cell biology. Gene transfer will not only increase our understanding of the pathophysiology of hearing loss, but also may provide gene therapy for disease.
Time course of nerve‐fiber regeneration in the noise‐damaged mammalian cochlea
Authors: Lawner Brian E. , Harding Gary W. , Bohne Barbara A. 
Published: July 2002

AbstractThe time course of events which are essential for nerve‐fiber regeneration in the mammalian cochlea was determined using a group of chinchillas that had been exposed for 3.5 hr to an octave band of noise with a center frequency of 4 kHz and a sound pressure level of 108 dB. The animals recovered from 40 min (0 days) to 100 days at which times their inner ears were fixed and the organs of Corti prepared for phase‐contrast and bright‐field microscopy as plastic‐embedded flat preparations. Selected areas identified in the flat preparations were semi‐thick and thin sectioned at radial or tangential angles for examination by bright‐field and transmission electron microscopy. The following time‐ordered events appeared critical for nerve‐fiber regeneration: (1) The area of the basilar membrane in which regeneration had a possibility of occurring showed signs of severe injury. Outer hair cells degenerated first followed by outer pillars, inner pillars, inner hair cells and other supporting cells; (2) Myelinated nerve fibers in the osseous spiral lamina became fragmented, starting at the distal ends of the fibers. This degeneration gradually extended back to Rosenthal's canal; (3) Fibrous processes, originating from Schwann‐like cells in the osseous spiral lamina, extended laterally on the basilar membrane; (4) Schwann cells lined up medial to the habenulae perforata in the areas of severest damage, apparently ready to migrate through the habenulae onto the basilar membrane; (5) Schwann‐cell nuclei appeared on the basilar membrane beneath the developing layer of squamous epithelium which was in the process of replacing the degenerated portion of the organ of Corti; (6) Regenerated nerve fibers with thin myelin sheaths or a simple investment of Schwann cell cytoplasm appeared in areas of total loss of the organ of Corti; and (7) The myelin sheaths on the regenerated nerve fibers gradually became thicker.
Cholinergic immunolesions by 192IgG‐saporin—a useful tool to simulate pathogenic aspects of alzheimer's disease
Authors: Roßner Steffen 
Published: July 2002

AbstractAlzheimer's disease, the most common cause of senile dementia, is characterized by intracellular formation of neurofibrillary tangles, extracellular deposits of beta amyloid as well as cerebrovascular amyloid accumulation and a profound loss of cholinergic neurons within the nucleus basalis Meynert with alterations in cortical neurotransmitter receptor densities. The use of the cholinergic immunotoxin 192IgG‐saporin allows for the first time study of the impact of cortical cholinergic deafferentation on cortical neurotransmission, learning, and memory without direct effects on other neuronal sytems. This model also allows the elucidation of contributions of cholinergic mechanisms to the establishment of other pathological features of Alzheimer's disease. The findings discussed here demonstrate that cholinergic immunolesions by 192IgG‐saporin induce highly specific, permanent cortical cholinergic hypoactivity and alterations in cortical neurotransmitter densities comparable to those described for Alzheimer's disease. The induced cortical cholinergic deficit also leads to cortical/hippocampal neurotrophin accumulation and reduced amyloid precursor protein (APP) secretion, possibly reflecting the lack of stimulation of postsynaptic M1/M3 muscarinic receptors coupled to protein kinase C. This immunolesion model should prove useful to test therapeutic strategies based on stimulation of cortical cholinergic neurotransmission or amelioration of pathogenic aspects of cholinergic degeneration in the basal forebrain. Application of the model to animal species that can developβ‐amyloid plaques could provide information about the contribution of cholinergic function to amyloidogenic APP processing.
Prenatal stress: consequences of glucocorticoids on hippocampal development and function
Authors: Takahashi Lorey K. 
Published: July 2002

AbstractPrenatally stressed offspring exhibit a variety of physiological and behavioral alterations. This paper highlights those alterations associated with prenatal stress‐induced elevations in glucocorticoid secretion. Three major alterations are identified that may be produced by glucocorticoid‐induced actions on the developing hippocampus. Changes include reductions in steroid receptors that bind endogenous glucocorticoids, enhanced secretion of stress hormones and increased reactivity or emotionality in stressful situations. Some of these alterations may be ameliorated by early postnatal environmental manipulations such as adoption and handling procedures. These latter results suggest that prenatal stress‐induced effects of glucocorticoids extend into the early postnatal period to produce long‐term hippocampal and behavioral alterations. Support for this hypothesis is based on studies demonstrating that the hippocampus undergoes considerable maturational changes during the early postnatal period such as establishing the regional distribution of corticosteroid receptor densities and development of hippocampal dentate gyrus cells as well as cholinergic systems. Hippocampal corticosteroid receptors are involved in the regulation of glucocorticoid negative feedback and hippocampal dentate gyrus and cholinergic development are influenced by endogenous glucocorticoids and are implicated in the development of defensive or stress‐induced behavior. The developing hippocampus appears especially vulnerable to alterations induced by prenatal stress‐induced elevations in glucocorticoids that continue to produce their effects throughout the early postnatal period.
Quantitative study of plasticity in the auditory nuclei of chick under conditions of prenatal sound attenuation and overstimulation with species specific and music sound stimuli
Authors: Wadhwa Shashi , Anand Phalguni , Bhowmick Deepika 
Published: July 2002

AbstractMorphological effects of prenatal sound attenuation and sound overstimulation by species specific and music sounds on the brainstem auditory nuclei of chick have been evaluated quantitatively. Changes in length, volume, neuron number, size of neuronal nuclei and glial numbers of second and third order auditory nuclei, n. magnocellularis (NM) and n. laminaris (NL), were determined from thionine‐stained serial sections of control and experimental groups on posthatch day 1 using stereological methods.Significant increase in volume of both auditory nuclei attributable to increase in length of nucleus, number and size of neurons, number of glia as well as neuropil was observed in response to both species specific and music overstimulation given during the critical period of development. The enhanced development of auditory nuclei in response to enriched environment prenatally indicates a positive effect of activity on neurons which may have clinical implications in addition to providing explanation for preference to auditory cues in the postnatal life.Reduction in neuron number with a small increase in proportion of cell nuclei of large size as well as an increase in glial numbers was seen in both NM and NL of the prenatally sound attenuated chicks. The increase in size of some neuronal nuclei may probably be evidence of enhanced synthesis of proteins involved in cell death or an attempt at recovery.The dissociated response of neurons and glia under sound attenuated and auditory stimulated conditions suggests that they are independently regulated by activity‐dependent signals with glia also being under influence of other signals for a role in removal of dead cell debris.
Increased SPARC expression promotes U87 glioblastoma invasion in vitro
Authors: Golembieski W.A. , Ge S. , Nelson K. , Mikkelsen T. , Rempel S.A. 
Published: July 2002

AbstractOur recent studies have focused on identifying invasion‐promoting genes that are expressed early in brain tumor progression. We identified and characterized SPARC (secreted protein acidic and rich in cysteine) as a potential candidate. To determine whether increased SPARC expression functionally promotes brain tumor invasion, SPARC was transfected into U87MG glioblastoma cells using the tetracycline‐off gene expression system. The parental cell line (U87MG), the parental transactivator‐transfected clone (U87T2) and three selected U87T2–SPARC‐transfected clones (A2bi, A2b2 and C2a4) were characterized for endogenous and transfected SPARC expression. In comparison to the parental or U87T2 cell lines, the SPARC‐transfected clones demonstrated: (1) morphological changes, (2) increased SPARC transcript and protein abundances that were down‐regulated by the tetracycline analog doxycycline, (3) perinuclear localization of the transfected SPARC (consistent with reported localization of SPARC in normal cells in culture) and (4) altered adhesion and increased invasion as assessed by the spheroid confrontation assay. These data indicate that increased SPARC expression contributes to U87 glioblastoma tumor invasion in vitro and that these cell lines will serve as useful reagents to investigate the mechanism(s) by which SPARC promotes this phenotype in vitro and in vivo.
Matrix metalloproteinases and their biological function in human gliomas
Authors: Chintala Shravan K. , Tonn Jorg C. , Rao Jasti S. 
Published: July 2002

AbstractGliomas, a type of devastating primary brain tumors, are distinct from other solid, nonneural primary neoplasms, in that they display extensive infiltrative invasive behavior but seldom metastasize to distant organs. This invasiveness into the surrounding normal brain tissue makes gliomas a major challenge for clinical intervention. Total surgical resection of gliomas is not possible, and recurrence of tumor growth is common; mean survival time is 8–12 months. Although substantial progress has been made recently toward understanding the behavior of gliomas, the mechanisms that facilitate invasion are still poorly documented. Clues to the invasion process have been ascertained through clarification of the key roles played by the extracellular matrix (ECM), cell‐adhesion molecules and matrix degrading proteases. Serine proteases and metalloproteinases have been implicated in glioma tumor cell‐invasion. Matrix metalloproteinases (MMPs) in particular can degrade almost all known ECM components and seem to play important roles in mediating glioblastoma tumor cell invasion. This review focuses on recent developments concerning the role of MMPs in the invasiveness of human gliomas.
Social separation in infant Cebus apella: patterns of behavioral and cortisol response
Authors: Byrne Gayle , Suomi Stephen J. 
Published: July 2002

Abstract34 infant tufted capuchins (Cebus apella) were separated from their social groups for a 2‐hour period and videotaped in isolation at the ages of 6 months and 1 year. Baseline and 2‐hour blood samples were measured for levels of serum cortisol. Compared to homecage baseline levels, passivity, locomotion and vocalizations increased during separation, while self‐directed behavior and environmental exploration decreased. Both behavioral and cortisol responses to separation showed individual stability over the 6 month period, although both responses were somewhat attenuated at the later age. There was little correlation between cortisol and behavior during separations. Females vocalized more than did males during separations and showed greater cortisol increases at 6 months of age. The pattern of behavioral response seen in the 2 hours following separation appeared to be more passive than the typical 'protest' response described in many nonhuman primates, and may reflect either the physical circumstances of the separation or a characteristic of species with relaxed social bonds and considerable allomothering available to infants.
Retrovirus producer cells encoding antisense VEGF prolong survival of rats with intracranial GS9L gliomas
Authors: Sasaki M. , Wizigmann‐Voos S. , Risau W. , Plate K.H. 
Published: July 2002

AbstractWith increasing size tumors are continually dependent on a functional blood vessel system to guarantee the supply with oxygen and nutrients. Vascular endothelial growth factor (VEGF) is a key mediator not only of developmental but also of hypoxia‐mediated and tumor‐induced angiogenesis. Gene therapy using antisense VEGF with the aim to inhibit tumor angiogenesis may be a successful strategy for the treatment of highly vascular and invasive malignant gliomas. We investigated whether retrovirus producer cells encoding antisense VEGF can be used for in vivo gene transfer. The full length mouse VEGF164 cDNA was cloned in a sense and antisense direction into the retroviral expression vector pLEN. pLEN–VEGF (sense) and pLEN–FGEV (antisense) expression vectors were used to transfect the packaging cell line GP+E86 and to establish ecotropic virus producer cell lines. GP+E86:LEN–FGEV (#5) cells showed high expression of antisense VEGF mRNA, whereas GP+E86:LEN–VEGF (#8) showed high expression of sense VEGF mRNA and active VEGF protein. Co‐implantation of GS‐9L cells with retrovirus producing cells containing the antisense VEGF construct into the brains of syngeneic rats showed a statistically significant inhibition of tumor growth and prolongation of survival time, while co‐implantation of retrovirus producer cells containing the sense VEGF expression vector resulted in an increasing tumor growth and reduced survival time of the rats compared to control animals. Histological analysis of the tumors co‐implanted with GP+E86:LEN–FGEV (#5) cells showed the suppression of angiogenesis, high degree of necrosis and no evidence of a significant immune response. Expression of antisense VEGF mRNA in these tumors was confirmed by in situ hybridization analysis. This is the first report demonstrating the potential utility of virus producer cells as in vivo gene transfer vehicles for antisense VEGF gene therapy of malignant gliomas.