2,230 research outputs found
CYP 2E1 mutant mice are resistant to DDC-induced enhancement of MPTP toxicity
No full textIn order to reach a deeper insight into the mechanism of diethyldithiocarbamate (DDC)-induced enhancement of MPTP toxicity in mice, we showed that CYP450 (2E1) inhibitors, such as diallyl sulfide (DAS) or phenylethylisothiocyanate (PIC), also potentiate the selective DA neuron degeneration in C57/bl mice. Furthermore we showed that CYP 2E1 is present in the brain and in the basal ganglia of mice (Vaglini et al., 2004). However, because DAS and PIC are not selective CYP 2E1 inhibitors and in order to provide direct evidence for CYP 2E1 involvement in the enhancement of MPTP toxicity, CYP 2E1 knockout mice (GONZ) and wild type animals (SVI) of the same genetic background were treated with MPTP or the combined DDC + MPTP treatment. In CYP 2E1 knockout mice, DDC pretreatment completely fails to enhance MPTP toxicity, although enhancement of MPTP toxicity was regularly present in the SVI control animals. The immunohistochemical study confirms our results and suggests that CYP 2E1 may have a detoxifying role
MPTP-induced model of Parkinson's disease in cytochrome P450 2E1 knockout mice
No full textEvidence for involvement of cytochrome P450 2E1 in the MPTP-induced mouse model of PD has been reported [Vaglini, F., Pardini, C., Viaggi, C., Bartoli, C., Dinucci, D., Corsini, G.U., 2004. Involvement of cytochrome P450 2E1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse model of Parkinson's disease. J. Neurochem. 91, 285-298]. We studied the sensitivity of Cyp2e1(-/-) mice to the acute administration of MPTP in comparison with their wild-type counterparts. In Cyp2e1(-/-) mice, the reduction of striatal DA content was less pronounced 7 days after MPTP treatment compared to treated wild-type mice. Similarly, TH immunoreactivity analysis of the substantia nigra of Cyp2e1(-/-) mice did not show any neuronal lesions after MPTP treatment. In contrast to this, wild-type animals showed a minimal but significant lesioning by the toxin as evaluated also by means of non-stereologic computerized assisted analysis of this brain area. Striatal levels of DA metabolites after 7 days were variably affected by the toxin, but consistent differences between the two animal strains were not observed. We evaluated short-term changes in the levels of striatal DA and its metabolites, and we monitored striatal MPP(+) levels. Striatal MPP(+) was cleared more rapidly in Cyp2e1(-/-) mice than in wild-type animals and, consistently, striatal DA content decreased faster in Cyp2e1(-/-) mice than in wild-type animals, and 3-methoxytyramine and HVA levels showed an early and sharp rise. Our findings suggest that Cyp2e1(-/-) mice are weakly sensitive to MPTP-induced brain lesions, markedly in contrast with a protective role of the enzyme as suggested previously. The differences observed between the knockout mice and their wild-type counterparts are modest and may be due to an efficient compensatory mechanism or genetic drift in the colonie
Aggregation of human neutrophils induced by phytohemagglutinin
No full textPhytohemagglutinin-induced aggregation of circulating neutrophils was studied in 13 normal subjects. The interference caused by various drugs (vinblastine, cytochalasin B, indomethacin, nicardipine and flunarizine) was tested. The modifications in the aggregation values induced by these drugs are in favour of an evident dependence of the phenomenon upon the trans-membrane flow of calcium ions and the calmodulin function and of a limited dependence upon the microtubular function
Role of excitatory amino-acids in diethyldithiocarbamate-induced cell death in mesencephalic cultures
No full textThe effects of diethyldithiocarbamate (DDC) and DDC plus glutamate on mesencephalic cell cultures were investigated. DDC 10 mu M was toxic for cell cultures as assessed by observation under a phase-contrast microscope and the drop in [H-3]dopamine uptake. Moreover, DDC 1 mu M greatly potentiated cell death induced by glutamate 10 and 50 mu M. (+)MK801, a selective non-competitive antagonist of NMDA receptors, completely prevented the toxicity of the two neurotoxins
A Novel Method to Produce Immobilised Biomolecular Concentration Gradients to Study Cell Activities: Design and Modelling
No full textAssessment and comparison of neural morphology through metrical feature extraction and analysis in neuron and neuron-glia cultures
No full textThe morphology of dissociated single cerebellar Purkinje cells obtained from wild-type P1 CD1 mice was assessed in the absence and in the presence of glia. A dedicated noninvasive technique based on optical microscopy was developed. Image processing algorithms were implemented to extract metrical features characterizing cell structure and dendritic arborization. The morphological features were analyzed in order to identify quantitative differences in Purkinje cell morphology due to interactions with astrocytes
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