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In Vitro Effects of Chronic Spirolide Treatment on Human Neuronal Stem Cell Differentiation and Cholinergic System Development
Version 2 2018-03-16, 13:36
Version 1 2018-03-14, 17:34
journal contribution
posted on 2018-03-08, 00:00 authored by Andrea Boente-Juncal, Aida G. Méndez, Carmen Vale, Mercedes R. Vieytes, Luis M. BotanaSpirolides
(SPX) are marine toxins, produced by dinoflagellates that act as potent
antagonists of nicotinic acetylcholine receptors. These compounds
are not toxic for humans, and since there are no reports of human
intoxications caused by this group of toxins they are not yet currently
regulated in Europe. Currently 13-desmethyl spirolide C, 13,19-didesmethyl
spirolide C, and 20-methyl spirolide G are commercially available
as reference materials. Previous work in our laboratory has demonstrated
that after 4 days of treatment of primary mice cortical neurons with
13-desmethyl spirolide C, the compound ameliorated the glutamate induced
toxicity and increased acetylcholine levels and the expression of
the acetylcholine synthesizing enzyme being useful both in vitro and
in vivo to decrease the brain pathology associated with Alzheimer’s
disease. In this work, we aimed to extend the study of the neuronal
effects of spirolides in human neuronal cells. To this end, human
neuronal progenitor cells CTX0E16 were employed to evaluate the in
vitro effect of spirolides on neuronal development. The results presented
here indicate that long-term exposure (30 days) of human neuronal
stem cells to SPX compounds, at concentrations up to 50 nM, ameliorated
the MPP+-induced neurotoxicity and increased the expression
of neuritic and dendritic markers, the levels of the choline acetyltransferase
enzyme and the protein levels of the α7 subunit of nicotinic
acetylcholine receptors. These effects are presumably due to the previously
described interaction of these compounds with nicotinic receptors
containing both α7 and α4 subunits. All together, these
data emphasize the idea that SPX could be attractive lead molecules
against neurodegenerative disorders.
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nicotinic acetylcholine receptorsCholinergic System Development Spirolidesmarine toxins50 nMα7 subunitreference materialsPrevious work13- desmethyl spirolide Ccompound ameliorated20- methyl spirolide Gnicotinic receptorsVitro Effectsdendritic markersneurodegenerative disordersChronic Spirolide Treatmentbrain pathologyacetylcholine synthesizing enzymeSPX compoundsprogenitor cells CTX 0Eacetylcholine levels4 daysα4 subunitsHuman Neuronal Stem Cell Differentiationprotein levelsMPPcholine acetyltransferase enzyme
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