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Benefit of 13-desmethyl spirolide C treatment in triple transgenic mouse model of Alzheimer disease: beta-amyloid and neuronal markers improvement
Benefit of 13-desmethyl spirolide C treatment in triple transgenic mouse model of Alzheimer disease: beta-amyloid and neuronal markers improvement
- Source :
- Curr Alzheimer Res, Curr Alzheimer Res, 2013, 10 (3), pp.279-89. ⟨10.2174/1567205011310030007⟩, ResearcherID
- Publication Year :
- 2012
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 18755828
- Volume :
- 10
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Current Alzheimer research
- Accession number :
- edsair.doi.dedup.....1fda06dc7915eb0372aa14e452510b3a
- Full Text :
- https://doi.org/10.2174/1567205011310030007⟩