title: Free and nanoencapsulated curcumin suppress β-amyloid-induced cognitive impairments in rats: involvement of BDNF and Akt/GSK-3β signaling pathway.
abstract: Alzheimer's disease (AD), a neurodegenerative disorder exhibiting progressive loss of memory and cognitive functions, is characterized by the presence of neuritic plaques composed of neurofibrillary tangles and β-amyloid (Aβ) peptide. Drug delivery to the brain still remains highly challenging for the treatment of AD. Several studies have been shown that curcumin is associated with anti-amyloidogenic properties, but therapeutic application of its beneficial effects is limited. Here we investigated possible mechanisms involved in curcumin protection against Aβ(1-42)-induced cognitive impairment and, due to its poor bioavailability, we developed curcumin-loaded lipid-core nanocapsules in an attempt to improve the neuroprotective effect of this polyphenol. Animals received a single intracerebroventricular injection of Aβ(1-42) and they were administered either free curcumin or curcumin-loaded lipid-core nanocapsules (Cur-LNC) intraperitoneally for 10days. Aβ(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 BDNF expression and Akt/GSK-3β signaling pathway, beyond tau hyperphosphorylation. Our findings demonstrate that administration of curcumin was effective in preventing behavioral impairments, neuroinflammation, tau hyperphosphorylation as well as cell signaling disturbances triggered by Aβ in vivo. Of high interest, Cur-LNC in a dose 20-fold lower presented similar neuroprotective results compared to the effective dose of free curcumin. Considered overall, the data suggest that curcumin is a potential therapeutic agent for neurocognition and nanoencapsulation of curcumin in LNC might constitute a promising therapeutic alternative in the treatment of neurodegenerative diseases such as AD.
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. Electronic address: juhoppe@hotmail.com.
authors: Juliana B
authors: JB
authors: Hoppe
authors: Karine
authors: K
authors: Coradini
authors: Rudimar L
authors: RL
authors: Frozza
authors: Claudia M
authors: CM
authors: Oliveira
authors: André B
authors: AB
authors: Meneghetti
authors: Andressa
authors: A
authors: Bernardi
authors: Elisa Simões
authors: ES
authors: Pires
authors: Ruy C R
authors: RC
authors: Beck
authors: Christianne G
authors: CG
authors: Salbego
mesh_terms: D016229:Amyloid beta-Peptides; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008568:Memory / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D019208:Brain-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D016708:Synaptophysin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D003474:Curcumin
keywords: Akt/GSK-3β pathway; Alzheimer’s disease; BDNF; Curcumin; Hippocampus; Lipid-core nanocapsules; β-Amyloid