Histopathologic Approaches to Chemical Toxicity Using Primary Cultures of Dissociated Neural Cells Grown in Chamber Slides

Bolon, Brad; Dorman, David C.; Bonnefoi, M.; Randall, Holly W.; Morgan, Kevin T.

doi:10.1177/019262339302100506

Cited by 15 publications

(9 citation statements)

References 15 publications

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“…The antimitotic agents AraC, FdU, and camptothecin were assayed for their abilities to decrease glial contamination in dissociated CST neuron cultures. Although a low concentration of FdU was moderately effective for decreasing glial contamination (data not shown), addition of all of the antimitotics generally decreased cell number, regardless of cell type, as has been previously reported (Bolon et al, 1993; Besirli et al, 2003). Because these antimitotic agents appeared to exert deleterious effects on neuronal survival and outgrowth, they were not included in further experiments (Supp.…”

Section: Resultssupporting

confidence: 81%

Corticospinal neurons respond differentially to neurotrophins and myelin‐associated glycoprotein in vitro

Richter

Roskams

2009

J of Neuroscience Research

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Elucidating the mechanisms that regulate the survival and outgrowth of corticospinal tract (CST) neurons and other CNS tracts will be a key component in developing novel approaches for the treatment of central nervous system (CNS) disorders, including stroke, spinal cord injury (SCI), and motor neuron disease (MND). However, the in vivo complexities of these diseases make a systematic evaluation of potential therapeutics that directly affect corticospinal regeneration or survival very challenging. Here, we use Thy1.2 transgenic mice expressing yellow fluorescent protein (YFP) in postnatal day 8 (P8) corticospinal neurons, as a source of CST neurons that have already established synapses in the spinal cord, to assess factors that influence neurite outgrowth and survival of axotomized CST neurons. After culture, YFP-positive corticospinal neurons represent an enriched neuronal population over other glia and interneurons, survive, and extend processes over time. YFP-positive CST neurons also continue to express the corticospinal markers CTIP2 and Otx1. CST neurons display different degrees of axon extension, dendritic branch length and elaboration, and neurite elongation in response to neurotrophin-3 and ciliary neurotrophic factor, and an inhibitory outgrowth response when cultured on myelin-associated glycoprotein. Some CST neurons are lost with extended culture, which provides a baseline from which we can also assess factors that enhance CST neuron survival. This assay thus allows us to assess independent aspects of CST axonal and dendritic outgrowth kinetics, which allows for the rapid and sensitive investigation of new therapies to address corticospinal neuron outgrowth in the context of CNS injury and neurodegenerative disorders.

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Section: Resultssupporting

confidence: 81%

Corticospinal neurons respond differentially to neurotrophins and myelin‐associated glycoprotein in vitro

Richter

Roskams

2009

J of Neuroscience Research

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“…Activation of JNK and p38 as well as subsequent induction of apoptosis may also contribute to the neurotoxicity of other environmental toxicants. It has become increasingly clear that many toxicants exert their toxic effects by inducing apoptosis (Bolon et al, 1993;Alison and Sarraf, 1995;Bulleit and Cui, 1998). For example, other heavy metals, including lead, mercury, and lithium, all induce neuronal apoptosis (D'Mello et al, 1994;Kunimoto, 1994;Sarafian et al, 1994;Oberto et al, 1996).…”

Section: Discussionmentioning

confidence: 99%

Arsenite-Induced Apoptosis in Cortical Neurons Is Mediated by c-Jun N-Terminal Protein Kinase 3 and p38 Mitogen-Activated Protein Kinase

2000

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c-Jun N-terminal protein kinase (JNK) and p38 mitogenactivated protein kinase are activated by stress and are implicated in regulation of apoptosis in several tissues. However, their contribution to stress-induced apoptosis in CNS neurons is not well defined. Here we investigated the role of JNK and p38 in cortical neuron apoptosis caused by sodium arsenite treatment. Sodium arsenite is an environmental toxicant that causes developmental defects in the CNS. Treatment of cortical neurons with sodium arsenite activated p38 and JNK3 but not JNK1 or JNK2. It also induced c-Jun phosphorylation. Furthermore, sodium arsenite induced cortical neuron apoptosis. This apoptosis was attenuated by SB203580, an inhibitor of p38, and by CEP-1347, an inhibitor of JNK activation. Expression of dominant-interfering mutants of the JNK or p38 pathways inhibited apoptosis induced by arsenite, whereas expression of constitutive active mutants for either pathway induced apoptosis. Moreover, the caspase inhibitor zVAD-fluoromethylketone as well as expression of bcl-2 or bcl-xL inhibited cortical neuron apoptosis induced by arsenite or by constitutive activation of JNK or p38. These data indicate that both JNK and p38 contribute to arsenite-induced apoptosis in primary CNS neurons, and this apoptosis requires the bcl-2-caspase pathway. This is the first evidence that a specific JNK isoform is differentially activated by stress and contributes to neuronal apoptosis.

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“…Thus the mechanism of malformations observed in various parts of fetal body is not well known. It was reported that injection of Ara-C to pregnant mice induced increased apoptosis of neuroepithelial cells in the fetal telencephalon 9 and Ara-C caused apoptosis in many different cell culture models [10][11][12] . However, due to the lack of reports regarding fetal cell apoptosis induced by transplacental exposure of Ara-C, little is known about the mechanism of fetotoxic effect of Ara-C including its relationship with cytotoxicity, i.e.…”

Section: Introductionmentioning

confidence: 99%

1-.BETA.-D-Arabinofuranosylcytosine (Ara-C)-induced Apoptosis in the Rat Fetal Tissues and Placenta

et al. 2003

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1-β-D-Arabinofuranosylcytosine (Ara-C), a cytidine analogue, inhibits DNA synthesis and is used for the treatment of myelogenous leukemia. On the other hand, it is also known that Ara-C has a teratogenic effect. In the present study, pregnant rats were treated with 250 mg/kg of Ara-C on day 13 of gestation, and fetal tissues and placentae were collected from 3 to 48 hours after treatment to examine the sequential histopathological changes induced by prenatal Ara-C treatment. The weights of fetuses and placentae and the thickness of the placental labyrinth zone were significantly reduced at 48 hours after treatment. In the fetal tissues such as central nervous system and mesenchymes and in the placental labyrinth zone, the number of pyknotic cells stained positively by the TUNEL method increased markedly after treatment with Ara-C. In most fetal tissues, the number began to increase from 3 to 6 hours and peaked at 9 to 12 hours after treatment. In the placental labyrinth zone, the number peaked at 6 hours after treatment. Electron microscopical features of the pyknotic cells consisted with the ultrastructural characteristics of apoptotic cells. In various fetal organs and placentae, abnormal induction of apoptosis is suggested to induce growth inhibition and have a certain relation to the malformations. Moreover, abnormal induction of apoptosis would have a deep connection with the cytotoxic effect of Ara-C which may affect proliferative cells in fetuses and placentae developing rapidly. (J Toxicol Pathol 2003; 16: 223-229)

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Histopathologic Approaches to Chemical Toxicity Using Primary Cultures of Dissociated Neural Cells Grown in Chamber Slides

Cited by 15 publications

References 15 publications

Corticospinal neurons respond differentially to neurotrophins and myelin‐associated glycoprotein in vitro

Corticospinal neurons respond differentially to neurotrophins and myelin‐associated glycoprotein in vitro

Arsenite-Induced Apoptosis in Cortical Neurons Is Mediated by c-Jun N-Terminal Protein Kinase 3 and p38 Mitogen-Activated Protein Kinase

1-.BETA.-D-Arabinofuranosylcytosine (Ara-C)-induced Apoptosis in the Rat Fetal Tissues and Placenta

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