کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7281865 | 1473934 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Imatinib methanesulfonate reduces hippocampal amyloid-beta and restores cognitive function following repeated endotoxin exposure
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
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چکیده انگلیسی
Alzheimer's disease (AD) is characterized, in part, by atrophy of the adult brain and increased presence of extracellular amyloid-beta (Aβ) plaques. Previous studies in our lab have shown that peripheral inflammation can lead to increased central Aβ and deficits in learning and memory. In order to determine whether Aβ accumulation in the brain is responsible for the learning deficits, we attempted to decrease peripheral production of Aβ in order to reduce central Aβ accumulation. It has previously been shown that Aβ is produced in large quantities in the liver, and is transferred across the blood-brain barrier (BBB). Recent research has shown that peripheral treatment with imatinib methanesulfonate salt (IM), known to interfere with the interaction between gamma (γ)-secretase and the γ-secretase activating protein (GSAP), decreases the cleavage of peripheral amyloid precursor protein into Aβ. Because IM poorly penetrates the BBB, we hypothesized that co-administration of IM with LPS would decrease peripheral production of Aβ in the presence of LPS-induced inflammation, leading to a decrease in Aβ accumulation in the hippocampus. We show that peripheral IM treatment eliminates hippocampal Aβ elevation that follows LPS-induced peripheral inflammation. Importantly, IM also eliminates the cognitive impairment seen following seven consecutive days of LPS administration, implicating Aβ peptides as a likely cause of these cognitive deficits.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain, Behavior, and Immunity - Volume 33, October 2013, Pages 24-28
Journal: Brain, Behavior, and Immunity - Volume 33, October 2013, Pages 24-28
نویسندگان
Marielle K. Weintraub, Courtney M. Bisson, Jessica N. Nouri, Benjamin T. Vinson, Micah J. Eimerbrink, Dinko Kranjac, Gary W. Boehm, Michael J. Chumley,