Optical and SPION-Enhanced MR Imaging Shows that trans-Stilbene Inhibitors of NF-κB Concomitantly Lower Alzheimer's Disease Plaque Formation and Microglial Activation in AβPP/PS-1 Transgenic Mouse Brain
| Autor: | Laurel O. Sillerud, David L. Vander Jagt, Lorraine M. Deck, Thomas A. Vander Jagt, Marco Bisoffi, Nathan O. Solberg, Jenette R. Vigil, Michael Garwood, Christina I. Brady, David C. Brown, Ryan Chamberlin, John E. Heidrich, Virginia Severns |
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| Rok vydání: | 2014 |
| Předmět: |
Genetically modified mouse
Pathology medicine.medical_specialty media_common.quotation_subject Metal Nanoparticles Hippocampus Mice Transgenic Plaque Amyloid Inflammation Resveratrol Ferric Compounds Article Amyloid beta-Protein Precursor Mice chemistry.chemical_compound Imaging Three-Dimensional Alzheimer Disease Stilbenes Presenilin-1 medicine Animals Humans Enzyme Inhibitors Internalization Neuroinflammation media_common Microglia Chemistry General Neuroscience Age Factors NF-kappa B Brain General Medicine Molecular biology Disease Models Animal Psychiatry and Mental health Clinical Psychology Neuroprotective Agents medicine.anatomical_structure Mutation Geriatrics and Gerontology medicine.symptom Ex vivo |
| Zdroj: | Journal of Alzheimer's Disease. 40:191-212 |
| ISSN: | 1875-8908 1387-2877 |
| DOI: | 10.3233/jad-131031 |
| Popis: | Alzheimer's disease (AD) is associated with a microglia-dependent neuroinflammatory response against plaques containing the fibrous protein amyloid-β (Aβ). Activation of microglia, which closely associate with Aβ plaques, engenders the release of pro-inflammatory cytokines and the internalization of Aβ fibrils. Since the pro-inflammatory transcription factor NF-κB is one of the major regulators of Aβ-induced inflammation, we treated transgenic amyloid-β protein protein/presenilin-1 (AβPP/PS1) mice for one year with a low dose (0.01% by weight in the diet) of either of two trans-stilbene NF-κB inhibitors, resveratrol or a synthetic analog LD55. The 3D distribution of Aβ plaques was measured ex vivo in intact brains at 60 μm resolution by quantitative magnetic resonance imaging (MRI) using blood-brain barrier-permeable, anti-AβPP-conjugated superparamagentic iron oxide nanoparticles (SPIONs). The MRI measurements were confirmed by optical microscopy of thioflavin-stained brain tissue sections and indicated that supplementation with either of the two trans-stilbenes lowered Aβ plaque density in the cortex, caudoputamen, and hippocampus by 1.4 to 2-fold. The optical measurements also included the hippocampus and indicated that resveratrol and LD55 reduced average Aβ plaque density by 2.3-fold and 3.1-fold, respectively. Ex vivo measurements of the regional distribution of microglial activation by Iba-1 immunofluorescence of brain tissue sections showed that resveratrol and LD55 reduced average microglial activation by 4.2- fold and 3.5-fold, respectively. Since LD55 lacked hydroxyl groups but both resveratrol and LD55 concomitantly reduced both Aβ plaque burden and neuroinflammation to a similar extent, it appears that the antioxidant potential of resveratrol is not an important factor in plaque reduction. |
| Databáze: | OpenAIRE |
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