Neuroprotective Effects of Resveratrol Against Aβ Administration in Rats are Improved by Lipid-Core Nanocapsules

被引：139

作者：

Frozza, Rudimar L. ^{[1
]}

Bernardi, Andressa ^{[2
]}

Hoppe, Juliana B. ^{[1
]}

Meneghetti, Andre B. ^{[1
]}

Matte, Aline ^{[1
]}

Battastini, Ana M. O. ^{[1
]}

Pohlmann, Adriana R. ^{[3
]}

Guterres, Silvia S. ^{[2
]}

Salbego, Christianne ^{[1
]}

机构：

[1] Univ Fed Rio Grande do Sul, Dept Bioquim, Programa Posgrad Bioquim, BR-90035003 Porto Alegre, RS, Brazil

[2] Univ Fed Rio Grande do Sul, Fac Farm, Programa Posgrad Ciencias Farmaceut, BR-90610000 Porto Alegre, RS, Brazil

[3] Univ Fed Rio Grande do Sul, Inst Quim, Programa Posgrad Quim, BR-91501970 Porto Alegre, RS, Brazil

来源：

MOLECULAR NEUROBIOLOGY | 2013年 / 47卷 / 03期

关键词：

Alzheimer's disease; Amyloid-beta peptide; Drug delivery; Hippocampus; Neuroprotection; Resveratrol; INDOMETHACIN-LOADED NANOCAPSULES; BLOOD-BRAIN-BARRIER; ALZHEIMERS-DISEASE; AMYLOID-BETA; NEURODEGENERATIVE DISORDERS; TRANS-RESVERATROL; DRUG-DELIVERY; PROTEIN; NANOPARTICLES; PATHWAY;

D O I：

10.1007/s12035-013-8401-2

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Alzheimer's disease (AD), a neurodegenerative disorder exhibiting a gradual decline in cognitive function, is characterized by the presence of neuritic plaques composed of neurofibrillary tangles and amyloid-beta (A beta) peptide. Available drugs for AD therapy have small effect sizes and do not alter disease progression. Several studies have been shown that resveratrol is associated with anti-amyloidogenic properties, but therapeutic application of its beneficial effects is limited. Here we compared the neuroprotective effects of free resveratrol treatment with those of resveratrol-loaded lipid-core nanocapsule treatment against intracerebroventricular injection of A beta 1-42 in rats. Animals received a single intracerebroventricular injection of A beta 1-42 (2 nmol), and 1 day after A beta infusion, they were administered either free resveratrol (RSV) or resveratrol-loaded lipid-core nanocapsules (5 mg/kg, each 12 h, intraperitoneally), for 14 days. A beta 1-42-infused animals showed a significant impairment on learning memory ability, which was paralleled by a significant decrease in hippocampal synaptophysin levels. Furthermore, animals exhibited activated astrocytes and microglial cells, as well as disturbance in c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-3 beta (GSK-3 beta) activation, beyond destabilization of beta-catenin levels. Our results clearly show that by using lipid-core nanocapsules, resveratrol was able to rescue the deleterious effects of A beta 1-42 while treatment with RSV presented only partial beneficial effects. These findings might be explained by the robust increase of resveratrol concentration in the brain tissue achieved by lipid-core nanocapsules. Our data not only confirm the potential of resveratrol in treating AD but also offer an effective way to improve the efficiency of resveratrol through the use of nanodrug delivery systems.

引用

页码：1066 / 1080

页数：15

共 77 条

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