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Posts Tagged ‘NIH’

Cellometer used in study to examine secondary effects of MAO inhibitors

Sara Barker | December 22, 2015 | No Comments | Cellometer User Publications

In the “catecholaldehyde hypothesis” of Parkinson’s disease neurodegeneration, cytoplasmic dopamine (DA) is converted to 3,4-dihydroxyphenylacetaldehyde (DOPAL) by the enzyme monoamine oxidase-A (MAO-A). DOPAL is a toxic substance, generating free radicals and inhibiting mitochondrial function. Scientists at NIH wanted to compare the abilities of currently available MAO-A and MAO-B inhibiting drugs at decreasing endogenous DOPAL levels. Using PC12 cells, six drugs were tested for their effects on DOPAL: MAO-A inhibitor clorygyline, three reversible MAO-A inhibitors, and the MAO-B inhibitors selegiline and rasagiline. The Cellometer was used to count the cells throughout experimentation. Clorgyline, rasagiline, and selegiline decreased DOPAL levels in both the cells and the media, while the reversible MAO-A inhibitors did not. The drugs also decreased dopamine synthesis and increased dopamine auto-oxidation. The results of this work suggest that the secondary effects of MAO inhibition should be studied more carefully in future clinical trials.

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Cellometer participates in study to ascertain rotenone mechanism of action

Sara Barker | December 15, 2015 | No Comments | Cellometer User Publications

A common hypothesis concerning the pathogenesis of Parkinson’s neurodegeneration suggests that cytoplasmic dopamine (DA) is converted to the auto-toxic 3,4-dihydroxyphenylacetaldehyde (DOPAL), which is neutralized by aldehyde dehydrogenase (ALDH). NIH researchers studied whether rotenone, a substance typically used to create in vitro models of Parkinson neurodegeneration, inhibits ALDH function. PC12 cells were exposed to various concentrations of rotenone in the presence or absence of F-dopamine. Catecholamine metabolism was then measured. The Cellometer maintained cell counts throughout experimentation. Rotenone increased DOPAL while decreasing dopamine levels in cell culture, but in a test tube, the DOPAL to DOPAC conversion by ALDH was not affected by rotenone. The authors used the data generated by this study to propose a novel mechanism of action for the selective dopaminergic toxicity of rotenone

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