Benefit of 13-desmethyl spirolide C treatment in triple transgenic mouse model of Alzheimer disease: beta-amyloid and neuronal markers improvement
| العنوان: | Benefit of 13-desmethyl spirolide C treatment in triple transgenic mouse model of Alzheimer disease: beta-amyloid and neuronal markers improvement |
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| المؤلفون: | Carmen Vale, Paz Otero, Luis M. Botana, Amparo Alfonso, Laurent Chabaud, Eva Alonso, Catherine Guillou, Lydia Gimenez-Llort, Alvaro Antelo |
| المساهمون: | Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC) |
| المصدر: | Curr Alzheimer Res Curr Alzheimer Res, 2013, 10 (3), pp.279-89. ⟨10.2174/1567205011310030007⟩ ResearcherID |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | Genetically modified mouse, Male, Magnetic Resonance Spectroscopy, Amyloid, Amyloid beta, medicine.medical_treatment, Intraperitoneal injection, Blotting, Western, Biological Availability, Mice, Transgenic, Pharmacology, Blood–brain barrier, Mass Spectrometry, 03 medical and health sciences, Mice, 0302 clinical medicine, In vivo, Alzheimer Disease, medicine, Animals, Spiro Compounds, Chromatography, High Pressure Liquid, 030304 developmental biology, Neurons, 0303 health sciences, Amyloid beta-Peptides, biology, business.industry, [CHIM.ORGA]Chemical Sciences/Organic chemistry, medicine.disease, 3. Good health, Disease Models, Animal, medicine.anatomical_structure, Neuroprotective Agents, Neurology, biology.protein, Female, Neurology (clinical), Alzheimer's disease, business, Marine toxin, 030217 neurology & neurosurgery |
| الوصف: | International audience; 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. |
| تدمد: | 1875-5828 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1fda06dc7915eb0372aa14e452510b3aTest https://pubmed.ncbi.nlm.nih.gov/23036025Test |
| رقم الانضمام: | edsair.doi.dedup.....1fda06dc7915eb0372aa14e452510b3a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 18755828 |
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