Spirolides are marine toxins that are not currently in the routine monitoring assays. Nicotinic receptors seem to
be the target of these compounds making them a promising pharmacological tool for related diseases as dementias as previously
shown in vitro. In the present work, the bioavailability of 13-desMethyl spirolide C (13-desMeC) in the brain and
in vivo effects were tested. Bioavailability was studied by ultra-performance liquid chromatography-mass spectrometry
and its effect over Alzheimer hallmarks was studied by Proton magnetic resonance spectroscopy (H-MRS) and western
blot. Only 2 minutes after its intraperitoneal injection it is found in brain and remains detectable even 24 hours post administration.
Based on previous works that showed beneficial effects in an in vitro model of Alzheimer´s disease (AD),
we studied the effect in the same mice, 3xTg-AD, in vivo. We found that 13-desMeC (11.9 ug/kg, i.p.) induced positive
effects on AD markers with an increase in N-acetyl aspartate (NAA) levels. These results were supported by an increase
in synaptophysin levels and also a decrease in the intracellular amyloid beta levels in the hippocampus of treated 3xTg-
AD versus non treated mice remarking the positive effects of this molecule in a well known model of AD.
These data indicate for the first time that 13-desMeC cross the blood brain barrier and shows in vivo beneficial effects
against AD after administration of low intraperitoneal doses of this marine toxin. This toxin may inspire a novel medical
treatment of age-related diseases.
Keywords: Spirolide, marine toxin, Alzheimer, resonance magnetic, tau, beta-amyloid
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