| First Author | Solberg NO | Year | 2014 |
| Journal | J Alzheimers Dis | Volume | 40 |
| Issue | 1 | Pages | 191-212 |
| PubMed ID | 24413613 | Mgi Jnum | J:351728 |
| Mgi Id | MGI:7663093 | Doi | 10.3233/JAD-131031 |
| Citation | Solberg NO, et al. (2014) Optical and SPION-enhanced MR imaging shows that trans-stilbene inhibitors of NF-kappaB concomitantly lower Alzheimer's disease plaque formation and microglial activation in AbetaPP/PS-1 transgenic mouse brain. J Alzheimers Dis 40(1):191-212 |
| abstractText | Alzheimer's disease (AD) is associated with a microglia-dependent neuroinflammatory response against plaques containing the fibrous protein amyloid-beta (Abeta). Activation of microglia, which closely associate with Abeta plaques, engenders the release of pro-inflammatory cytokines and the internalization of Abeta fibrils. Since the pro-inflammatory transcription factor NF-kappaB is one of the major regulators of Abeta-induced inflammation, we treated transgenic amyloid-beta protein protein/presenilin-1 (AbetaPP/PS1) mice for one year with a low dose (0.01% by weight in the diet) of either of two trans-stilbene NF-kappaB inhibitors, resveratrol or a synthetic analog LD55. The 3D distribution of Abeta plaques was measured ex vivo in intact brains at 60 mum resolution by quantitative magnetic resonance imaging (MRI) using blood-brain barrier-permeable, anti-AbetaPP-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 Abeta 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 Abeta 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 Abeta plaque burden and neuroinflammation to a similar extent, it appears that the antioxidant potential of resveratrol is not an important factor in plaque reduction. |
