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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.
J Alzheimers Dis. 2014; 40(1):191-212.JA

Abstract

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.

Authors+Show Affiliations

Departments of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA.The Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, USA.Departments of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA.Department of Chemistry and Chemical Biology, University of New Mexico, Albuquerque, NM, USA.Quatros LLC, Albuquerque, NM, USA.Departments of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA.Departments of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA.Quatros LLC, Albuquerque, NM, USA.The Center for Magnetic Resonance Research and Department of Radiology, University of Minnesota Medical School, Minneapolis, MN, USA.Departments of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA.Departments of Pathology, University of New Mexico School of Medicine, Albuquerque, NM, USA.Departments of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA Quatros LLC, Albuquerque, NM, USA.Departments of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM, USA.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

Language

eng

PubMed ID

24413613

Citation

Solberg, Nathan O., et al. "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." Journal of Alzheimer's Disease : JAD, vol. 40, no. 1, 2014, pp. 191-212.
Solberg NO, Chamberlin R, Vigil JR, et al. 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. J Alzheimers Dis. 2014;40(1):191-212.
Solberg, N. O., Chamberlin, R., Vigil, J. R., Deck, L. M., Heidrich, J. E., Brown, D. C., Brady, C. I., Vander Jagt, T. A., Garwood, M., Bisoffi, M., Severns, V., Vander Jagt, D. L., & Sillerud, L. O. (2014). 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. Journal of Alzheimer's Disease : JAD, 40(1), 191-212. https://doi.org/10.3233/JAD-131031
Solberg NO, et al. 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. J Alzheimers Dis. 2014;40(1):191-212. PubMed PMID: 24413613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Solberg,Nathan O, AU - Chamberlin,Ryan, AU - Vigil,Jenette R, AU - Deck,Lorraine M, AU - Heidrich,John E, AU - Brown,David C, AU - Brady,Christina I, AU - Vander Jagt,Thomas A, AU - Garwood,Michael, AU - Bisoffi,Marco, AU - Severns,Virginia, AU - Vander Jagt,David L, AU - Sillerud,Laurel O, PY - 2014/1/14/entrez PY - 2014/1/15/pubmed PY - 2014/10/31/medline KW - LD55 KW - NF-κB KW - SPIONs KW - magnetic resonance imaging KW - microglia KW - neuroinflammation KW - resveratrol KW - transgenic mice SP - 191 EP - 212 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 40 IS - 1 N2 - 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. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/24413613/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_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-131031 DB - PRIME DP - Unbound Medicine ER -