title: Neuroprotective Effects of Engineered Polymeric Nasal Microspheres Containing Hydroxypropyl-β-cyclodextrin on β-Amyloid (1-42)-Induced Toxicity.
abstract: β-Amyloid (Aβ) plaques are the key neurotoxic assemblies in Alzheimer disease. It has been suggested that an interaction occurs between membrane cholesterol and Aβ aggregation in the brain. Cyclodextrins can remove cholesterol from cell membranes and change receptor function. This study aimed to investigate the effect of hydroxypropyl-β-cyclodextrin (HP-CD) polymeric microspheres, based on chitosan or sodium alginate, on the levels of lipid peroxidation, reactive oxygen species production, and mitochondrial function in brain synaptosomes. The effect of microspheres on DNA fragmentation, the expression of Bcl-2, Bax, and Apex1 mRNAs in rat hippocampus after Aβ(1-42) peptide-induced neurotoxicity was also evaluated. Comparison with HP-CD raw material was performed. Aβ(1-42) treatment significantly decreased the mitochondrial activity of Apex1 and Bcl-2 mRNAs, induced DNA fragmentation, and increased mRNA levels of Bax. Treatment with HP-CD microspheres against Aβ(1-42) significantly reduced DNA fragmentation and increased the Bcl-2/Bax mRNA ratio and mitochondrial function. In addition, HP-CD microspheres used against Aβ(1-42) decreased the levels of lipid peroxidation and reactive oxygen species production. These results indicate that nasally administered spray-dried HP-CD microspheres are able to provide protection against Aβ(1-42)-induced neurotoxicity, due to the suppressed levels of oxidative stress and apoptotic signals in the rat hippocampus.
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ege University, Bornova, Izmir 35100, Turkey; Department of Neurosciences, Health Science Institute, Ege University, Bornova, Izmir 35100, Turkey.
authors.forename: Ayfer
authors.initials: A
authors.lastname: Yalcin
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari 07100, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Soddu
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ege University, Bornova, Izmir 35100, Turkey.
authors.forename: Ezgi
authors.initials: E
authors.lastname: Turunc Bayrakdar
authors.affiliation: Department of Histology and Embryology, Faculty of Medicine, Ege University, Bornova, Izmir 35100, Turkey.
authors.forename: Yigit
authors.initials: Y
authors.lastname: Uyanikgil
authors.affiliation: Department of Neurosciences, Health Science Institute, Ege University, Bornova, Izmir 35100, Turkey; Department of Physiology, Faculty of Medicine, Ege University, Bornova, Izmir 35100, Turkey.
authors.forename: Lutfiye
authors.initials: L
authors.lastname: Kanit
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ege University, Bornova, Izmir 35100, Turkey.
authors.forename: Guliz
authors.initials: G
authors.lastname: Armagan
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari 07100, Italy.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Rassu
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari 07100, Italy. Electronic address: eligav@uniss.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Gavini
authors.affiliation: Department of Chemistry and Pharmacy, University of Sassari, Sassari 07100, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Giunchedi
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin / Q000008:administration & dosage / Q000627:therapeutic use*; D000281:Administration, Intranasal; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D053938:DNA Fragmentation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008863:Microspheres; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010446:Peptide Fragments / Q000633:toxicity*; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D000073738:2-Hydroxypropyl-beta-cyclodextrin
keywords: apoptosis; gene expression; hydroxypropyl-β-cyclodextrin; microsphere; nasal administration; neuroprotective effect; oxidative stress; rat hippocampus; spray drying; β-amyloid