bluuebunny/crossref_metadata_2025_split huggingface dataset:
Constitutive overexpression of the basic helix‐loop‐helix Nex1/MATH‐2 transcription factor promotes neuronal differentiation of PC12 cells and neurite regeneration
Authors: Uittenbogaard Martine , Chiaramello Anne 
Published: August 2002

AbstractElucidation of the intricate transcriptional pathways leading to neural differentiation and the establishment of neuronal identity is critical to the understanding and design of therapeutic approaches. Among the important players, the basic helix‐loop‐helix (bHLH) transcription factors have been found to be pivotal regulators of neurogenesis. In this study, we investigate the role of the bHLH differentiation factor Nex1/MATH‐2 in conjunction with the nerve growth factor (NGF) signaling pathway using the rat phenochromocytoma PC12 cell line. We report that the expression of Nex1 protein is induced after 5 hr of NGF treatment and reaches maximal levels at 24 hr, when very few PC12 cells have begun extending neurites and ceased cell division. Furthermore, our study demonstrates that Nex1 has the ability to trigger neuronal differentiation of PC12 cells in the absence of neurotrophic factor. We show that Nex1 plays an important role in neurite outgrowth and has the capacity to regenerate neurite outgrowth in the absence of NGF. These results are corroborated by the fact that Nex1 targets a repertoire of distinct types of genes associated with neuronal differentiation, such as GAP‐43, βIII‐tubulin, and NeuroD. In addition, our findings show that Nex1 up‐regulates the expression of the mitotic inhibitor p21WAF1, thus linking neuronal differentiation to cell cycle withdrawal. Finally, our studies show that overexpression of a Nex1 mutant has the ability to block the execution of NGF‐induced differentiation program, suggesting that Nex1 may be an important effector of the NGF signaling pathway. © 2002 Wiley‐Liss, Inc.
Inhibition by R(+) or S(–) pramipexole of caspase activation and cell death induced by methylpyridinium ion or beta amyloid peptide in SH‐SY5Y neuroblastoma
Authors: Abramova Nicole A. , Cassarino David S. , Khan Shaharyar M. , Painter Terry W. , Bennett James P. 
Published: August 2002

AbstractCell models of neurodegenerative diseases (NDD) can involve expression of mutant nuclear genes associated with Mendelian forms of the diseases or effects of toxins believed to replicate essential disease features. Death produced by exposing neural cells to methylpyridinium ion (MPP+) or neurotoxic beta amyloid (BA) peptides is frequently used to study features of the sporadic, most prevalent forms of Parkinson's disease (PD) and Alzheimer's disease (AD), respectively. We examined in replicating SH‐SY5Y human neuroblastoma cells the release of cytochrome C into cytoplasm, activation of caspases 9 and 3, and loss of calcein retention as markers of the “mitochondrial” pathway of cell death. Exposure to 5 mM MPP+, which induces apoptotic cell death within 18–24 hr, released cytochrome C within 4 hr, activated caspases 9 and 3, and reduced calcein accumulation. BA 25–35 peptide produced more rapid and greater elevations of caspase 3 activity; no effects were observed with the nontoxic BA 35–25 reverse sequence. The dependence on mitochondrial transition pore (MTP) activity of MPP+‐induced caspase activations was demonstrated by preincubation with bongkreckic acid, which blocked elevations of caspases 9 and 3. Stereoisomers of pramipexole (PPX), a free radical scavenger and inhibitor of MTP opening, inhibited caspase activation (MPP+ and BA) and restored calcein accumulation (MPP+). Our results demonstrate that MPP+ and BA can induce cell death through MTP‐dependent activation of caspase cascades. PPX stereoisomers interfere with activation of these cell death pathways and may be useful clinically as neuroprotectants in PD and AD and related diseases. © 2002 Wiley‐Liss, Inc.
Gene transfer into the central nervous system in vivo using a recombinanat lentivirus vector
Authors: Lai Zhennan , Brady Roscoe O. 
Published: August 2002

AbstractGene transfer vectors derived from human immunodeficiency virus (HIV‐1) efficiently transduce nondividing cells and may provide for the delivery of their gene products to discrete regions of the brain. We investigated whether stable gene transduction can be achieved in cells of the central nervous system (CNS) in vivo by a potent lentivirus vector. The herpes simplex virus type 1 protein VP22 has been known to facilitate intercellular protein transport and thereby provides an opportunity to increase the effectiveness of therapeutic genes by enhancing the delivery of their protein products. We developed a lentiviral vector construct expressing enhanced green fluorescent protein (EGFP) fused at its N‐terminus to the herpes simplex virus VP22. In order to determine expression of the fusion protein in specific cells such as neurons in the CNS, a neuron‐specific promoter was also placed into the construct. The viral vectors were injected directly into the striatum and hippocampus of mouse brains. We found that the lentivirus vector efficiently and stably transduced nondividing cells in the CNS with transgene expression for over 3 months. We also show that the delivery of VP22‐EGFP fusion protein encoded by the lentivirus was effectively transported between neuronal cells via axons in vivo. Doubly labeled experiments revealed that our lentiviral vector is capable of delivering gene products to neurons and astrocytes in CNS. The data also demonstrate that up to 90% of the CNS cells transduced by our lentiviral vector under the control of the neuronal promoter are neurons. Published 2002 Wiley‐Liss, Inc.
Differential effects of glucocorticoids and gonadal steroids on glutathione levels in neuronal and glial cell systems
Authors: Schmidt A.J. , Krieg J.‐C. , Vedder H. 
Published: August 2002

AbstractThe aim of the present study was to investigate the short‐ and long‐term effects of glucocorticoids [corticosterone (CORT), dexamethasone (DEX), 6‐methylprednisolone (6‐MP)] and gonadal steroids [17β‐estradiol (E2), progesterone (PROG), testosterone (TEST)] on the levels of the antioxidant glutathione (GSH) in different cell systems of the CNS (neuronal hippocampal HT22 cells, primary hippocampal and neocortical brain cells, and C6 glioma cells). In HT22 cells, steroids exerted mainly long‐term effects. Significant increases of GSH levels were detectable after a 24 hr treatment with 10−7 M of DEX (122% ± 5%), 6‐MP (208% ± 32%), E2 (134% ± 10%), and TEST (155% ± 17%). A significant decrease occurred after incubation with PROG for 24 hr (79% ± 9%). In primary hippocampal cultures, a 24 hr treatment with DEX (140% ± 8%), E2 (123% ± 6%), and PROG (118% ± 5%) led to significant increases of the GSH levels, whereas, in neocortical primary cultures, only an incubation with E2 increased GSH (149% ± 8%). In C6 cells, hormone treatment led to both significant short‐term (1 hr: CORT 114% ± 5%, DEX 90% ± 3%, E2 88% ± 3%; 3 hr: DEX 115% ± 5%, E2 122% ± 6%, TEST 78% ± 4%) and significant long‐term (24 hr: CORT 74% ± 4%, 6‐MP 84% ± 5%, E2 115% ± 6%, PROG 91% ± 4%, TEST 116% ± 5%) effects. In summary, we were able to demonstrate differential effects of steroids on GSH levels in different cellular CNS models, showing an important influence of steroids and especially E2 on antioxidative cellular functions in neuronal and glial cells. © 2002 Wiley‐Liss, Inc.
Role of HuD and other RNA‐binding proteins in neural development and plasticity
Authors: Perrone‐Bizzozero Nora , Bolognani Federico 
Published: August 2002

AbstractTranscription factors have traditionally been viewed as the main determinants of gene expression. Yet, in recent years it has become apparent that RNA‐binding proteins also play a critical role in determining the levels of expression of a large number of genes. Once mRNAs are transcribed, RNA‐binding proteins can control all subsequent steps in their function, from alternative splicing and translation to mRNA transport and stability. In the nervous system, a large number of genes are regulated post‐transcriptionally via the interaction of their mRNAs with specific RNA‐binding proteins. This type of regulation is particularly important in the control of the temporal and spatial pattern of gene expression during neural development. This review will discuss the function of the embryonic lethal abnormal vision (ELAV)/Hu family of nervous system‐specific RNA‐binding proteins, with a special emphasis on HuD, a member of this family that controls GAP‐43 mRNA stability and expression. In addition, we will present recent findings on other neural RNA‐binding proteins: the ribonucleoprotein K homology (KH)‐domain proteins, Fragile X mental retardation protein (FMRP), quakinguiable protein (QKI), and Nova‐1. Together with the ELAV/Hu family, these proteins are essential for proper neural development and in some cases for plasticity in the mature brain. The biological significance of these proteins is evident not only by their evolutionary conservation but also by the magnitude of problems arising from autoimmune reactions against them or from mutations affecting their expression or function. © 2002 Wiley‐Liss, Inc.
Identification of Gas6, a putative ligand for Sky and Axl receptor tyrosine kinases, as a novel neurotrophic factor for hippocampal neurons
Authors: Funakoshi Hiroshi , Yonemasu Tomoko , Nakano Toru , Matumoto Kunio , Nakamura Toshikazu 
Published: August 2002

AbstractSky (also known as “Tyro3” and “Rse”) is a member of the Axl/Sky/Mer receptor tyrosine kinase family and has two immunoglobulin‐like repeats and two fibronectin type III‐like repeats in the extracellular domain. Gas6 is a ligand for all members of the Axl family, each of which (Axl, Sky, and c‐Mer) has different affinities to Gas6. Physiological functions of Sky and Gas6 in the nervous system are not well understood, despite their importance, which is suggested by Sky structural features and its predominant expression in the brain. We found in the RNase protection assays that gas6 and sky mRNAs are expressed in the adult rat hippocampus and are similarly regulated during development. Expression levels were low during embryonic stages but gradually increased during development and reached the highest level in adulthood. Sky, but not Axl, immunoreactivity was observed in the adult hippocampus. Recombinant rat Gas6 attenuated hippocampal neuronal cell death that was caused by serum starvation in vitro, indicating that Gas6 is a novel neurotrophic factor for hippocampal neurons. Gas6 showed regulated expression in the sciatic nerve after nerve transection. Therefore, Sky and Gas6 have neurotrophic roles in the nervous system. © 2002 Wiley‐Liss, Inc.
Hypothermia and thiopentone sodium: Individual and combined neuroprotective effects on cortical cultures exposed to prolonged hypoxic episodes
Authors: Varathan Sriranganathan , Shibuta Satoshi , Shimizu Tomoaki , Varathan Vidya , Mashimo Takashi 
Published: August 2002

AbstractBecause there are many conflicting reports on cerebroprotective effects of hypothermia and barbiturates, we examined the degree of neuroprotection at defined temperatures (normothermia, 37°C; mild hypothermia, 32°C; deep hypothermia, 22°C; and profound hypothermia, 17°C) and various concentrations (low, 4 μM; moderate, 40 μM; and high, 400 μM) of thiopentone sodium (TPS), alone and in combination in cortical cultures exposed to prolonged hypoxia (24–48 hr). The survival rate of embryonic day (E)16 Wistar rat cortical neurons was evaluated on photomicrographs before and after experiments. During the 24‐hr hypoxic period, the survival rate of neurons was maximal with combinations of mild hypothermia with 40 μM (91.6 ± 0.7%) and 400 μM TPS (90.8 ± 0.7%) or deep hypothermia combined with all concentrations of TPS (4 μM, 90.6 ± 1.0%; 40 μM, 91.4 ± 0.8%; 400 μM, 91.8 ± 1.2%). During 48 hr hypoxia, the highest survival rate was seen with the combination of deep hypothermia and either 40 μM (90.9 ± 0.6%) or 400 μM (91.1 ± 1.4%) TPS. In the presence of profound hypothermia in combination with all concentrations of TPS, the survival rate was significantly reduced (P< 0.01) compared to combined application of either mild or deep hypothermia with TPS. In summary, maximal neuroprotection was attained with hypothermia and TPS in combination rather than applied individually, during prolonged hypoxic episodes (24– 48 hr). During a 24‐hr hypoxic period, both mild and deep hypothermia combined with a clinically relevant concentration of TPS (40 μM) offered the highest neuroprotection. Only deep hypothermia provided maximal neuroprotection when combined with 40 μM TPS, during 48‐hr hypoxia. Combination of profound hypothermia and TPS did not confer considerable neuroprotection during long lasting hypoxia. © 2002 Wiley‐Liss, Inc.
Δ9‐tetrahydrocannabinol increases endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons: Involvement of CB1 receptors
Authors: Tomasini Maria Cristina , Ferraro Luca , Bebe Berta Wonjie , Tanganelli Sergio , Cassano Tommaso , Cuomo Vincenzo , Antonelli Tiziana 
Published: August 2002

AbstractThe effects of the principal psychoactive component of marijuana, Δ9‐tetrahydrocannabinol (Δ9‐THC), on endogenous extracellular glutamate levels in primary cultures of rat cerebral cortex neurons were investigated. Locally applied Δ9‐THC (0.03, 3, 300, and 1,000 nM) concentration‐dependently increased basal extracellular glutamate levels (+18% ± 11%, +54% ± 10%, +90% ± 14%, +149% ± 33% vs. basal). The facilitatory effects of Δ9‐THC (3 and 300 nM) on cortical glutamate were fully counteracted in the presence of the selective CB1 receptor antagonist SR141716A (10 nM) and by replacement of the normal Krebs‐Ringer bicarbonate buffer with a low‐Ca2+ (0.2 mM) medium. Δ9‐THC application also induced an enhancement in K+‐evoked glutamate levels. These findings suggest that an increase in cortical glutamatergic transmission mediated by local CB1 receptor activation may underlie some of the psychoactive and behavioral effects of acute marijuana consumption. © 2002 Wiley‐Liss, Inc.
Hippocampal brain‐derived neurotrophic factor gene regulation by exercise and the medial septum
Authors: Berchtold Nicole C. , Kesslak J. Patrick , Cotman Carl W. 
Published: August 2002

AbstractBrain‐derived neurotrophic factor (BDNF) enhances synaptic plasticity and neuron function. We have reported that voluntary exercise increases BDNF mRNA levels in the hippocampus; however, mechanisms underlying this regulation have not been defined. We hypothesized that medial septal cholinergic and/or gamma amino butyric acid (GABA)ergic neurons, which provide a major input to the hippocampus, may regulate the baseline gene expression and exercise‐dependent gene upregulation of this neurotrophin. Focal lesions were produced by medial septal infusion of the saporin‐linked immunotoxins 192‐IgG‐saporin or OX7‐saporin. 192‐IgG‐saporin produced a selective and complete loss of medial septal cholinergic neurons with no accompanying GABA loss. Baseline BDNF mRNA was reduced in the hippocampus of sedentary animals, but exercise‐induced gene upregulation was not impaired, despite complete loss of septo‐hippocampal cholinergic afferents. OX7‐saporin produced a graded lesion of the medial septum characterized by predominant GABA neuron loss with less reduction in the number of cholinergic cells. OX7‐saporin lesion reduced baseline hippocampal BDNF mRNA and attenuated exercise‐induced gene upregulation, in a dose‐dependent manner. These results suggest that combined loss of septal GABAergic and cholinergic input to the hippocampus may be important for exercise‐dependent BDNF gene regulation, while cholinergic activity on its own is not sufficient. These results are discussed in relation to their implications for aging and Alzheimer's disease. © 2002 Wiley‐Liss, Inc.
Altered apolipoprotein D expression in the brain of patients with Alzheimer disease
Authors: Belloir Bénédicte , Kövari Enikö , Surini‐Demiri Maria , Savioz Armand 
Published: August 2002

AbstractThe etiology of late‐onset Alzheimer disease is poorly understood. Predisposing factors such as the apolipoprotein E4 allele, as well as protective factors (e.g., antioxidants) have been proposed to play a role in the disease's process. A search for predisposing factors contributing to sporadic late‐onset Alzheimer disease was initiated using the differential display technique. RNA expression profiles of the entorhinal cortex and the cerebellum of Alzheimer‐diseased and normal patients were compared. The entorhinal cortex is the first brain region to accumulate neurofibrillary tangles during disease progression, whereas the cerebellum is spared. In the Alzheimer cases of this study, one signal showing preferential expression in the entorhinal cortex corresponded to the apolipoprotein D gene. This preferential expression might be genuine at the RNA level as suggested by the in situ hybridization method used. In addition, immunohistochemical experiments showed higher percentages of Apolipoprotein D reactive pyramidal neurons in the entorhinal cortex and region 1 of Ammon's horn in diseased patients. This increase correlated with the number of neurofibrillary tangles in Alzheimer as well as in normal patients. Colocalization of Apolipoprotein D proteins and neurofibrillary tangles in the same neuron was rare. Thus, these results suggest that in Alzheimer disease and aging, apolipoprotein D gene expression is increased in stressed cortical neurons before they possibly accumulate neurofibrillary tangles. J. Neurosci. Res. 64:61–69, 2001. © 2001 Wiley‐Liss, Inc.
Conduction of impulses by axons regenerated in a Schwann cell graft in the transected adult rat thoracic spinal cord
Authors: Pinzon Alberto , Calancie Blair , Oudega Martin , Noga Brian R. 
Published: August 2002

AbstractCentral nervous system axons regenerate into a Schwann cell implant placed in the transected thoracic spinal cord of an adult rat. The present study was designed to test whether these regenerated axons are capable of conducting action potentials. Following the transection and removal of a 4‐ to 5‐mm segment of the thoracic spinal cord (T8–T9), a polymer guidance channel filled with a mixture of adult rat Schwann cells and Matrigel was grafted into a 4‐ to 5‐mm‐long gap in the transected thoracic spinal cord. The two cut ends of the spinal cord were eased into the guidance channel openings. Transected control animals received a channel containing Matrigel only. Three months after implantation, electrophysiological studies were performed. Tungsten microelectrodes were used for monopolar stimulation of regenerated axons within the Schwann cell graft. Glass microelectrodes were used to record responses in the spinal cord rostral to the stimulation site. Evoked responses to electrical stimulation of the axon cable were found in two out of nine Schwann cell‐grafted animals. These responses had approximate latencies in the range of those of myelinated axons. No responses were seen in any of the Matrigel‐grafted animals. Histological analysis revealed that the two cases that showed evoked potentials had the largest number of myelinated axons present in the cable. This study demonstrates that axons regenerating through Schwann cell grafts in the complete transected spinal cord can produce measurable evoked responses following electrical stimulation. J. Neurosci. Res. 64:533–541, 2001. © 2001 Wiley‐Liss, Inc.
Identification of living oligodendrocyte developmental stages by fractal analysis of cell morphology
Authors: Bernard Frédéric , Bossu Jean‐Louis , Gaillard Stéphane 
Published: August 2002

AbstractThe Mandelbrot's fractal dimension (D), a measure of shape complexity, has been used to quantify the complex morphology of living cells. Previous studies on glial cells have shown that as cells increase in morphological complexity, their “D” value increases, suggesting that “D” could be used to estimate their stage of differentiation. In the present study the box‐counting method was used to calculate the “D” values of rat cerebellar oligodendrocytes during their differentiation in primary culture. These values were correlated with the immunoreactivity of cells to antigenic markers commonly used for assessing their stages of differentiation: A2B5, O4 and anti‐galactocerebroside (Gal‐C). Our results show that changes of the fractal dimension during differentiation follow the well known pattern of markers expression by these cells. These results demonstrate that A2B5‐, O4‐, and Gal‐C‐expressing oligodendrocytes can be confidently estimated from their respective fractal dimension values. Based on this immunocytochemical calibration, the calculation of “D” allows an easy and fast determination of the developmental stage of living (unstained) oligodendrocytes before the study of their physiological characteristics. Using this method we precisely identified living oligodendrocyte progenitors and early pro‐oligodendrocytes expressing voltage‐activated sodium currents that is a common characteristic of these two immature developmental stages (Sontheimer et al. [1989b] Neuron 2:1135–1145). J. Neurosci. Res. 65:439–445, 2001. © 2001 Wiley‐Liss, Inc.
Type of employment, work–family conflict and well‐being: a comparative study
Authors: Parasuraman Saroj , Simmers Claire A. 
Published: August 2002

AbstractThe study examined the impact of work and family role characteristics on work–family conflict, and indicators of psychological well being among self‐employed and organizationally employed women and men. Results show that employment type and gender have independent main effects on several of the study variables. Self‐employed persons enjoy greater autonomy and schedule flexibility at work, and report higher levels of job involvement and job satisfaction than those employed in organizations. However, they also experience higher levels of work–family conflict, and lower family satisfaction than organizational employees. The findings suggest that there are trade‐offs between the costs and benefits of self‐employment, and that business ownership is not a panacea for balancing work and family role responsibilties. Directions for future research are discussed. Copyright © 2001 John Wiley & Sons, Ltd.
Job insecurity and crossover of burnout in married couples
Authors: Westman Mina , Etzion Dalia , Danon Esti 
Published: August 2002

AbstractWe investigated crossover of burnout between spouses in 98 married couples in an organization undergoing downsizing. Burnout was found to be associated with feelings of job insecurity, self‐control and social undermining. Using SEM, findings supported the crossover of burnout from husbands to wives and the impact of burnout on undermining behavior. They also supported the research hypothesis of a direct relationship between job insecurity and burnout among husbands but not among wives. Sense of control was found to have a negative impact on burnout and on the spouse's undermining behavior and a positive impact on the spouse's sense of control. Copyright © 2001 John Wiley & Sons, Ltd.
The interactive effects of procedural justice and exchange ideology on supervisor‐rated commitment
Authors: Witt L. A. , Kacmar K. Michele , Andrews Martha C. 
Published: August 2002

AbstractMatched data collected from 143 employees and their immediate supervisors of a private sector organization indicated that employee perceptions of procedural justice were only related to supervisor‐rated affective commitment among employees with a strong exchange ideology. That is, individuals motivated by a fair exchange exhibited fewer affective commitment behaviors when they viewed the environment as unfair than when they perceived it to be fair. Individuals comparatively indifferent to a fair exchange did not alter their affective commitment behaviors regardless of the level of perceived environmental fairness. These results illustrate the importance of considering individual differences in exchange ideology when attempting to alter the work environment for the purpose of increasing commitment. Implications for research and management practice are presented. Copyright © 2001 John Wiley & Sons, Ltd.