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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2009-5-11
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pubmed:abstractText |
Neuroinflammation has been linked to the pathologies of Alzheimer's disease (AD), however, its effects on beta-amyloid (Abeta) burden are unclear. This study investigated the role of nuclear factor kappa B (NF-kappaB) in regulating neuroinflammation and Abeta deposition in a transgenic mouse model of AD. The APPswe/PS1dE9 mice and their wild-type controls received either the NF-kappaB inhibitor pyrrolidine dithiocarbamate (PDTC, i.p. 50 mg/kg daily) or saline starting at 7 months of age for 5 months. Expression of cyclooxygenase-2 (COX-2), tissue necrosis factor alpha (TNFalpha) precursor protein and microtubule-associated protein 2 was determined, and astrogliosis was assessed. Hippocampal and cortical levels of Abeta(1-40) and Abeta(1-42) were measured using ELISA. PDTC treatment effectively suppressed NF-kappaB signaling in APPswe/PS1dE9 mice as evidenced by the abolishment of COX-2 and TNFalpha induction. Inhibition of NF-kappaB further attenuated astrogliosis in the transgenic AD mice, yet markedly increased cerebral Abeta(1-42) burden. Our findings suggest that NF-kappaB can mediate induction of COX-2, TNFalpha and astrogliosis in APPswe/PS1dE9 mice. Additionally, these results support the idea that neuroinflammation contributes to the clearance of Abeta.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Peptides,
http://linkedlifedata.com/resource/pubmed/chemical/Amyloid beta-Protein Precursor,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclooxygenase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Microtubule-Associated Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mtap2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Ptgs2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Pyrrolidines,
http://linkedlifedata.com/resource/pubmed/chemical/Thiocarbamates,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/pyrrolidine dithiocarbamic acid
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1873-7544
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
16
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pubmed:volume |
161
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
53-8
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19286451-Alzheimer Disease,
pubmed-meshheading:19286451-Amyloid,
pubmed-meshheading:19286451-Amyloid beta-Peptides,
pubmed-meshheading:19286451-Amyloid beta-Protein Precursor,
pubmed-meshheading:19286451-Animals,
pubmed-meshheading:19286451-Astrocytes,
pubmed-meshheading:19286451-Cerebral Cortex,
pubmed-meshheading:19286451-Cyclooxygenase 2,
pubmed-meshheading:19286451-Hippocampus,
pubmed-meshheading:19286451-Injections, Intraperitoneal,
pubmed-meshheading:19286451-Mice,
pubmed-meshheading:19286451-Mice, Transgenic,
pubmed-meshheading:19286451-Microtubule-Associated Proteins,
pubmed-meshheading:19286451-Mutation,
pubmed-meshheading:19286451-NF-kappa B,
pubmed-meshheading:19286451-Protein Precursors,
pubmed-meshheading:19286451-Pyrrolidines,
pubmed-meshheading:19286451-Thiocarbamates,
pubmed-meshheading:19286451-Tumor Necrosis Factor-alpha
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pubmed:year |
2009
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pubmed:articleTitle |
Suppression of nuclear factor kappa B ameliorates astrogliosis but not amyloid burden in APPswe/PS1dE9 mice.
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pubmed:affiliation |
Division of Pharmaceutical Sciences and Graduate Neuroscience Program, University of Wyoming, College of Health Sciences, Department 3375, 1000 East University Avenue, Laramie, WY 82071-3375, USA.
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pubmed:publicationType |
Journal Article,
Research Support, N.I.H., Extramural
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