Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027819 (neuroblastoma)
 27,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present experiments were aimed to determine the extent to which differentiated neuroblastoma cells may serve as a donor source for neural transplantation studies. Rodent-derived C1300 and human-derived LA-N-2 cells stained positively for choline acetyltransferase in vitro whether left untreated or rendered amitotic with mitomycin C/bromodeoxyuridine (Brdu) treatment. The two cell lines in both mitotic and differentiated states were subsequently transplanted into the hippocampus of rats that had previously undergone posterodorsal medial septal lesions. The undifferentiated cells continued to proliferate and formed large masses in the host brain within 7 days after implantation. When differentiated with mitomycin C/Brdu, the cells were autoradiographically visualized in large numbers 7 days following transplantation. Fewer cells were observed at the 30 and 120 test intervals. At the later time points the C1300 cells were found primarily within the host parenchyma while the LA-N-2 cells were found predominantly in the subependymal region below the hippocampus. These differentiated cells were also able to attenuate the cognitive dysfunction produced by medial septal lesions. However, an exact neurochemical mechanism cannot presently be ascribed to this effect since the cells failed to stain for choline acetyltransferase in vivo. At no time did differentiated cell grafts appear to revert to a neoplastic state nor was a significant immunological response observed. These findings, in concordance with other studies by our group, suggest that neuroblastoma cell lines may prove to be a practical source of donor tissue for neural transplants.
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PMID:Neuroblastoma cells in neural transplants: a neuroanatomical and behavioral analysis. 362 Sep 80

Two types of cognitive impairment in the rat are compared: deficits arising after damage to the forebrain cholinergic projection system perikarya induced by chronic alcohol treatment or excitotoxic lesions as a model for cholinergic dysfunction in neurodegenerative disease; and impairment after intrahippocampal ischaemic CA1 cell loss induced by occlusion of vertebral and carotid arteries (four vessel occlusion: 4 VO), resembling the cerebral consequences of heart attack in man. Findings to date indicate that cholinergic depletion disrupts performance on a broad range of tasks, suggesting a deficit in attention, whereas ischaemic damage induces a relatively specific impairment in spatial learning and precise localisation. Functional recovery from both types of brain damage has been observed following neural transplantation, but the mechanisms of action appear to differ. In animals with cholinergic damage, donor tissue from a variety of sources promoted functional recovery, including cholinergic-rich homografts from two different regions of the foetal brain (basal forebrain and pontomesencephalon), grafts of primary cells enriched with glia, and cultured neuroblastoma cells, provided that the grafts are placed in the terminal areas of cholinergic projections (cortex and/or hippocampus) and not in the damaged cell body regions (basal forebrain or medial septal area). In contrast, in animals with CA1 cell loss, only homotypic grafts dissected from the foetal CA1 field, and not from the CA3 or dentate gyrus fields, promoted functional recovery, when placed in the alveus, close to the damaged host CA1 area. These findings suggest that whereas grafts in cholinergic depleted animals may exert their functional effects through non-specific synaptic links with host neurons and/or release of trophic factors, CA1 field grafts may serve to bridge or repair the damaged host hippocampal circuit.
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PMID:Graft-induced recovery of cognitive function after diffuse and focal brain damage: implications for neural transplantation in man. 775 97

Nervous system involvement in systemic lupus erythematosus (SLE) includes a wide array of manifestations some of which have been associated with specific autoantibodies. These include reactivity to surface neuronal and lymphocyte antigens, ribosomal P and cardiolipin. The aim of the present study was to examine the association between cognitive abnormalities and these autoantibodies in an unselected female population of SLE patients. Using a battery of standardized neuropsychological tests, cognitive impairment was identified in 15/70 (21%) SLE patients compared to 1/25 (4%) patients with rheumatoid arthritis and 1/23 (4%) healthy subjects (P = 0.04). Circulating antineuronal antibodies were measured by indirect immunofluorescence using human neuroblastoma cell lines IMR-6 and SK-N-SH. Lymphocytotoxic antibodies were measured by microcytotoxicity. Antibodies to ribosomal P and cardiolipin were measured by ELISA. Antineuronal antibodies were detected in 34%, lymphocytotoxic antibodies in 47%, anti-P antibodies in 17% and anticardiolipin antibodies in 24% of patients. In the cognitively impaired and unimpaired SLE patients there was no significant difference in the prevalence of antineuronal antibodies (33 vs 35%), lymphocytotoxic antibodies (40 vs 50%), anti-P antibodies (20 vs 17%) or anticardiolipin antibodies (7 vs 29%). The titre and isotype of autoantibodies were also similar in both groups. These results suggest that autoantibodies which have previously been associated with nervous system manifestations of SLE are not likely to be directly involved in the pathogenesis of cognitive dysfunction.
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PMID:Cognitive impairment and autoantibodies in systemic lupus erythematosus. 846 22

Rifampicin, an antibiotic widely used in tuberculosis therapy, is known to exert psychotropic side effects in some patients. Recently, rifampicin has been reported to activate the glucocorticoid receptor (GR) in human hepatocytes. Because there is evidence that increased levels of glucocorticoids may induce cognitive impairment, sometimes culminating in depression, the side effects of rifampicin may result from GR activation in central nerve cells. Therefore, we used reporter gene assays to determine whether rifampicin displays glucocorticoid-like effects in human neuroblastoma SK-N-MC cells or mouse hippocampal HT22 cells. Rifampicin was unable to elicit any detectable transactivation of GR in both cell types, whereas cortisol or dexamethasone led to a potent transcriptional response. Rifampicin was also inactive in the same HepG2 cell line that was originally used to demonstrate the effect of rifampicin on GR. Moreover, rifampicin was unable to compete with dexamethasone for binding to GR. Finally, by blocking the multidrug resistance P-glycoprotein transporter (a xenobiotic extrusion pump) with verapamil or cyclosporin A, we excluded the possibility that the lack of effect by rifampicin was due to its export from the cell. Our results establish that rifampicin does not activate GR, and rule out the hypothesis that the psychotropic side effects of rifampicin treatment are a consequence of GR activation.
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PMID:Rifampicin is not an activator of glucocorticoid receptor. 1072 19

Previous studies have demonstrated that acetylcholinesterase (AChE) promotes the assembly of amyloid-beta-peptides into neurotoxic amyloid fibrils and is toxic for chick retina neuronal cultures and neuroblastoma cells. Moreover, AChE is present in senile plaques in Alzheimer's disease (AD) brains. Here we have studied the effect of AChE on astrocytes and hippocampal neurons in vivo. Morphological as well as behavioral disturbances were analyzed after intrahippocampal injection of AChE. Rats were trained in the Morris water maze and assayed for behavioral parameters. Neuronal cell loss was found in the upper leaf of the dentate gyrus in rats injected with AChE in comparison with control animals. Glial fibrillary acidic protein immunoreactivity showed astrocytic hypertrophy and the magnitude of the response was associated with neuronal cell loss. Behavioral results show that injection of AChE produces cognitive impairment demonstrated by an altered water maze performance including (i) a higher escape latency score, (ii) a decreased spatial acuity and (iii) a shorter time of swimming in the platform quadrant. These findings indicate that a local increment in neuronal AChE concentration at the mammalian hippocampus, such as those present in amyloid deposits, may play a role in triggering neuropathological and behavioral changes such as those observed in AD brains.
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PMID:Acetylcholinesterase induces neuronal cell loss, astrocyte hypertrophy and behavioral deficits in mammalian hippocampus. 1296 66

Induction of cyclooxygenase-2 (COX-2) in the brain of people infected with human immunodeficiency virus type 1 (HIV-1) has been proposed as a cause of cognitive impairment in AIDS dementia. Here, we have analyzed the molecular mechanism by which its induction takes place in neuroblastoma cells. The HIV-1 envelope protein gp120 was able to induce COX-2 mRNA and protein in several human neuroblastoma cell lines, which express CXCR4 and CCR5 but not CD4. Moreover, gp120 induces COX-2 promoter transcription. Sequential deletions of the promoter show that deletion of a distal nuclear factor-kappaB (NF-kappaB) site abrogated gp120-dependent transcription. More importantly, overexpression of NF-kappaB inhibitory subunit, IkappaBalpha, completely abrogated gp120-induced COX-2 activity. However, transfection of p65/relA NF-kappaB was not enough to induce COX-2 transcription, suggesting that NF-kappaB was necessary but not sufficient to control COX-2 transcription induced by gp120. In addition to NF-kappaB, activating protein-1 (AP-1) but not nuclear factor of activated T cells (NFAT)-dependent transcription was induced by gp120. Transfection of a dominant negative mutant c-Jun protein, TAM-67, efficiently blocked the induction of COX-2 promoter by gp120, confirming AP-1 requirement. Moreover, gp120 rapidly activates the c-Jun amino-terminal kinase (JNK) and p38 mitogen-activated protein kinase phosphorylation. The importance of NF-kappaB and AP-1 in COX-2 promoter and protein induction was corroborated by using pharmacological NF-kappaB, p38 and JNK inhibitors.
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PMID:Human immunodeficiency virus type 1 envelope glycoprotein 120 induces cyclooxygenase-2 expression in neuroblastoma cells through a nuclear factor-kappaB and activating protein-1 mediated mechanism. 1600 69

The beneficial effects of Omega n - 3 polyunsaturated fatty acids (n - 3 PUFA) in situations of cognitive impairment may be associated with enhanced neuronal growth. Since neuronal growth is impaired in n - 3 PUFA deficiency, and enhanced by certain vitamins and trace elements, the effects of n - 3 PUFA, vitamin and mineral cell complex (VMC) and their association on neuronal growth were investigated in cultured rat neuroblastoma cells. Treatment of cells for 3 days with n - 3 PUFA significantly enhanced neurite length without affecting the number of neurites or cells. VMC significantly increased cell number without affecting neurite length or their number. Combined n - 3 PUFA and VMC significantly enhanced all three growth parameters. The data confirm the growth promoting effects of n - 3 PUFA and VMC in cultured neurons over a relatively short time frame.
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PMID:Evidence for growth-promoting effects of omega n - 3 fatty acids alone and in combination with a specific vitamin and mineral complex in rat neuroblastoma cells. 1666 2

The developing nervous system has long been recognized as a primary target site for lead (Pb)-induced toxicity. Pb-exposure causes cognitive dysfunction, growth retardation, hyperactivity and neurochemical deficits in animals and humans. In the present study the effects of 17-beta-estradiol on human SH-SY5Y neuroblastoma cells in culture exposed to low-levels of Pb were assessed. The cells were exposed to Pb (0.01-10 microM) for 48 h and cell proliferation was determined by the MTT reduction assay. Pb significantly inhibited the proliferation and growth of neuroblastoma cells in a concentration-dependent manner. A 50% inhibition (IC50) in the proliferation of cells was observed with 5 microM Pb. Exposure of cells to Pb (5 microM) for 48 h resulted in a significant increase (+732% of control) in caspase-3 activity, an indicator of apoptosis and total cellular prostaglandin E2 level (+1180% of control), marker of programmed cell death/neuronal cell loss. Pretreatment with 17-beta-estradiol (10 nM) effectively blocked the effects of Pb on caspase-3 activity but not prostaglandin E2 level. Further, Pb but not 17-beta-estradiol in a concentration (0.1-10 microM)-dependent manner effectively decreased (38-84%) the cellular concentration of glutathione (GSH), an important intracellular antioxidant. However, the effect of Pb on GSH level was effectively blocked when pretreated with 17-beta-estradiol. The data indicate that even low concentrations of Pb can be detrimental and potentially toxic to the developing brain. In conclusion, these results suggest that at least some of the neurotoxic effects of Pb may be mediated by apoptosis, which by pretreatment with 17-beta-estradiol can be prevented. This study further confirms previous reports of 17-beta-estradiol acting as a neuroprotective and antiapoptotic agent during induced toxic stress conditions.
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PMID:Protective effect of 17-beta-estradiol in human neurocellular models of lead exposure. 1667 63

Opsoclonus-myoclonus ataxia syndrome is a paraneoplastic syndrome of cerebellar damage associated with neuroblastoma. The authors assessed psychiatric symptoms of opsoclonus-myoclonus ataxia syndrome in 17 children, who were 16 months to 12(1/2) years of age. Psychiatric symptoms examined included disruptive behavior, affective dysregulation, irritability, impulsivity, cognitive impairment, and poor attention.
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PMID:Mood and behavioral dysfunction with opsoclonus-myoclonus ataxia. 1672 Aug 3

Alzheimer's disease (AD) is a senile dementia characterized by amyloid plaques, neurofibrillary tangles, and synaptic and cell loss. The "amyloid cascade" hypothesis suggests that amyloid-beta (Abeta), the peptide deposited as amyloid plaques, is the primary insult in AD. However, debate continues over the mechanism of Abeta toxicity and whether fibrillar or oligomeric Abeta is the active species of the peptide that ultimately causes the synaptic loss and dementia associated with AD. Brain-derived neurotrophic factor (BDNF) is required for survival and function of cells compromised in AD. Decreased BDNF causes defects in long-term potentiation and memory and correlates with cognitive decline. We previously demonstrated that BDNF reduction occurs early in the course of AD, suggesting that decreased BDNF may promote neuronal dysfunction in AD. We also demonstrated that three of seven human BDNF transcripts are specifically downregulated in AD. What pathological feature(s) of AD leads to the decreased BDNF is unknown. In this study, we administered both fibrillar and oligomeric conformations of Abeta(1-42) to differentiated SH-SY5Y, a human neuroblastoma cell line, and measured both phosphorylated cAMP response element-binding protein (CREB), a regulator of BDNF transcription, and BDNF total mRNA. We found that oligomeric but not fibrillar preparations of Abeta(1-42) significantly decrease both phosphorylated CREB and total BDNF mRNA. Furthermore, oligomeric Abeta(1-42) decreases BDNF transcripts IV and V in these cells, demonstrating that Abeta(1-42) downregulates the major BDNF transcript decreased in vivo in the AD brain. Thus, oligomeric Abeta(1-42) could compromise neuronal function, causing memory loss and cognitive dysfunction by downregulation of BDNF in AD.
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PMID:Oligomeric amyloid decreases basal levels of brain-derived neurotrophic factor (BDNF) mRNA via specific downregulation of BDNF transcripts IV and V in differentiated human neuroblastoma cells. 1734


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