کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8259530 | 1534635 | 2016 | 41 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Role of P-glycoprotein in mediating rivastigmine effect on amyloid-β brain load and related pathology in Alzheimer's disease mouse model
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کلمات کلیدی
ABCA1ChEIsGLT-1APPAβGFAPBSA - BSAbovine serum albumin - آلبومین سرم گاوamyloid-β - آمیلوئید βACh - آهAcetylcholine - استیل کولینFormic acid - اسید فرمیکAlzheimer's disease - بیماری آلزایمرBBB - سد خونی مغزیBlood–brain barrier - سد خونی مغزیGlial fibrillary acidic protein - پروتئین اسیدی فیبریلاسیون گلایالamyloid precursor protein - پروتئین پیش ماده آمیلوئی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Role of P-glycoprotein in mediating rivastigmine effect on amyloid-β brain load and related pathology in Alzheimer's disease mouse model Role of P-glycoprotein in mediating rivastigmine effect on amyloid-β brain load and related pathology in Alzheimer's disease mouse model](/preview/png/8259530.png)
چکیده انگلیسی
Recently, we showed that rivastigmine decreased amyloid-β (Aβ) brain load in aged rats by enhancing its clearance across the blood-brain barrier (BBB) via upregulation of P-glycoprotein (P-gp) and low-density lipoprotein receptor-related protein 1 (LRP1). Here, we extend our previous work to clarify P-gp role in mediating rivastigmine effect on Aβ brain levels and neuroprotection in a mouse model of Alzheimer's disease (AD) that expresses different levels of P-gp. APPSWE mice were bred with mdr1a/b knockout mice to produce littermates that were divided into three groups; APP+/mdr1+/+, APP+/mdr1+/â and APP+/mdr1â/â. Animals received rivastigmine treatment (0.3 mg/kg/day) or vehicle for 8 weeks using Alzet osmotic mini-pumps. ELISA analysis of brain homogenates for Aβ showed rivastigmine treatment to significantly decrease Aβ brain load in APP+/mdr1+/+ by 25% and in APP+/mdr1+/â mice by 21% compared to their vehicle treated littermates, but not in APP+/mdr1â/â mice. In addition, rivastigmine reduced GFAP immunostaining of astrocytes by 50% and IL-1β brain level by 43% in APP+/mdr1+/+ mice, however its effect was less pronounced in P-gp knockout mice. Moreover, rivastigmine demonstrated a P-gp expression dependent neuroprotective effect that was highest in APP+/mdr1+/+ > APP+/mdr1+/â>APP+/mdr1â/â as determined by expression of synaptic markers PSD-95 and SNAP-25 using Western blot analysis. Collectively, our results suggest that P-gp plays important role in mediating rivastigmine non-cholinergic beneficial effects, including Aβ brain load reduction, neuroprotective and anti-inflammatory effects in the AD mouse models.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 4, April 2016, Pages 778-787
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease - Volume 1862, Issue 4, April 2016, Pages 778-787
نویسندگان
Loqman A. Mohamed, Jeffrey N. Keller, Amal Kaddoumi,