Molecular Neurobiology

, Volume 47, Issue 3, pp 1066–1080 | Cite as

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

  • Rudimar L. Frozza
  • Andressa Bernardi
  • Juliana B. Hoppe
  • André B. Meneghetti
  • Aline Matté
  • Ana M. O. Battastini
  • Adriana R. Pohlmann
  • Sílvia S. Guterres
  • Christianne Salbego
Article

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.

Keywords

Alzheimer’s disease Amyloid-β peptide Drug delivery Hippocampus Neuroprotection Resveratrol 

Notes

Acknowledgments

This study was supported by the following Brazilian agencies: Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). The authors thank PRONEX CNPq-FAPERGS (#10/0048-4). RL Frozza and JB Hoppe were recipients of Brazilian CNPq fellowships. A Bernardi was the recipient of a CAPES Post-doctoral fellowship.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Rudimar L. Frozza
    • 1
  • Andressa Bernardi
    • 2
  • Juliana B. Hoppe
    • 1
  • André B. Meneghetti
    • 1
  • Aline Matté
    • 1
  • Ana M. O. Battastini
    • 1
  • Adriana R. Pohlmann
    • 3
  • Sílvia S. Guterres
    • 2
  • Christianne Salbego
    • 1
  1. 1.Programa de Pós-Graduação em Bioquímica, Departamento de BioquímicaUniversidade Federal do Rio Grande do Sul—UFRGSPorto AlegreBrazil
  2. 2.Programa de Pós-Graduação em Ciências Farmacêuticas, Faculdade de FarmáciaUniversidade Federal do Rio Grande do Sul—UFRGSPorto AlegreBrazil
  3. 3.Programa de Pós-Graduação em Química, Instituto de QuímicaUniversidade Federal do Rio Grande do Sul—UFRGSPorto AlegreBrazil

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