title: Neuroprotective effects of resveratrol against Aβ administration in rats are improved by lipid-core nanocapsules.
abstract: 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-β (Aβ) 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 Aβ1-42 in rats. Animals received a single intracerebroventricular injection of Aβ1-42 (2 nmol), and 1 day after Aβ infusion, they were administered either free resveratrol (RSV) or resveratrol-loaded lipid-core nanocapsules (5 mg/kg, each 12 h, intraperitoneally), for 14 days. Aβ1-42-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-3β (GSK-3β) activation, beyond destabilization of β-catenin levels. Our results clearly show that by using lipid-core nanocapsules, resveratrol was able to rescue the deleterious effects of Aβ1-42 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.
authors: Programa de Pós-Graduação em Bioquímica, Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul-UFRGS, Rua Ramiro Barcelos, 2600 Porto Alegre, Rio Grande do Sul 90035-003, Brazil. rlfrozza@gmail.com
authors: Rudimar L
authors: RL
authors: Frozza
authors: Andressa
authors: A
authors: Bernardi
authors: Juliana B
authors: JB
authors: Hoppe
authors: André B
authors: AB
authors: Meneghetti
authors: Aline
authors: A
authors: Matté
authors: Ana M O
authors: AM
authors: Battastini
authors: Adriana R
authors: AR
authors: Pohlmann
authors: Sílvia S
authors: SS
authors: Guterres
authors: Christianne
authors: C
authors: Salbego
mesh_terms: D016229:Amyloid beta-Peptides / Q000008:administration & dosage* / Q000633:toxicity; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D007276:Injections, Intraventricular; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053769:Nanocapsules / Q000737:chemistry*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D055550:Protein Stability / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use; D013569:Synapses / Q000187:drug effects / Q000473:pathology; D014018:Tissue Distribution / Q000187:drug effects; D051176:beta Catenin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D008055:Lipids; D053769:Nanocapsules; D018696:Neuroprotective Agents; D013267:Stilbenes; D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D048031:JNK Mitogen-Activated Protein Kinases; D038362:Glycogen Synthase Kinase 3; D000077185:Resveratrol