title: Benefit of 13-desmethyl spirolide C treatment in triple transgenic mouse model of Alzheimer disease: beta-amyloid and neuronal markers improvement.
abstract: 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.
authors.affiliation: Departamento de Farmacología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Lugo, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Alonso
authors.forename: Paz
authors.initials: P
authors.lastname: Otero
authors.forename: Carmen
authors.initials: C
authors.lastname: Vale
authors.forename: Amparo
authors.initials: A
authors.lastname: Alfonso
authors.forename: Alvaro
authors.initials: A
authors.lastname: Antelo
authors.forename: Lydia
authors.initials: L
authors.lastname: Giménez-Llort
authors.forename: Laurent
authors.initials: L
authors.lastname: Chabaud
authors.forename: Catherine
authors.initials: C
authors.lastname: Guillou
authors.forename: Luis M
authors.initials: LM
authors.lastname: Botana
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology*; D016229:Amyloid beta-Peptides / Q000187:drug effects*; D000818:Animals; D001682:Biological Availability; D015153:Blotting, Western; D002851:Chromatography, High Pressure Liquid; D004195:Disease Models, Animal; D005260:Female; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D013141:Spiro Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: C517170:13-desmethylspirolide C; D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D013141:Spiro Compounds