کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
7279322 | 1473896 | 2018 | 37 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inflammation, insulin signaling and cognitive function in aged APP/PS1 mice
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کلمات کلیدی
IKKβTLR4AβmTORERK2MWMPKCMAPK - MAPKRWM - RWMamyloid-β - آمیلوئید βNeuroinflammation - التهاب عصبیAlzheimer’s disease - بیماری آلزایمرMemory - حافظهInsulin sensitivity - حساسیت به انسولینextracellular signal-regulated kinase 2 - خارج سلولی تنظیم شده با سیگنال کیناز 2Aging - سالخوردگیCytokines - سیتوکین هاInsulin signalling - سیگنالینگ انسولینCognitive function - عملکرد شناختیMorris water maze - ماز آب آب موریسORT - محلMechanistic target of rapamycin - هدف مکانیکی رپامایسینNovel Object Recognition task - وظیفه شناسایی شیء رمانProtein kinase C - پروتئین کیناز سیmitogen-activated protein kinase - پروتئین کیناز فعال با mitogenToll-like receptor 4 - گیرنده تله مانند 4Learning - یادگیری
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
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چکیده انگلیسی
Cognitive dysfunction and neuroinflammation are typical in Alzheimer's disease (AD), but are also associated with normal aging, albeit less severely. Insulin resistance in the brain has been demonstrated in AD patients and is thought to be involved in AD pathophysiology. Using 15-18â¯month-old APP/PS1 mice, this study measured peripheral and central insulin signaling and sensitivity, inflammatory markers in brain and plasma and oxidative stress and synapse density in the brain. Novel object recognition, Morris water maze and reversal water maze tasks were performed to assess cognitive function in aged APP/PS1 mice and wild type littermates. Glucose tolerance and insulin sensitivity were similar in APP/PS1 mice and wild type controls, however IRS-1 pSer616 was increased in cortex and dentate gyrus of APP/PS1 mice. Recognition and spatial memory was impaired in both APP/PS1 and wild type mice, however learning impairments were apparent in APP/PS1 mice. Expression of GLP-1 receptor, ERK2, IKKβ, mTOR, PKCθ, NF-κB1 and TLR4 was similar between aged APP/PS1 mice and age-matched wild types. Compared to age-matched wild type mice, IFNγ and IL-4 were increased in brains of APP/PS1 mice. These results suggest that normal aging may be associated with enhanced neuroinflammation, oxidative stress, and cognitive decline, however distinctions are apparent in the brain of APP/PS1 mice in terms of inflammation and insulin signaling and in certain cognitive domains. Demarcation of pathological events that distinguish AD from normal aging will allow for improvements in diagnostic tools and the development of more effective therapeutics.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain, Behavior, and Immunity - Volume 70, May 2018, Pages 423-434
Journal: Brain, Behavior, and Immunity - Volume 70, May 2018, Pages 423-434
نویسندگان
Paul Denver, Andrew English, Paula L. McClean,