Title of article :
Effect of Magnetic Tacrine-Loaded Chitosan Nanoparticles on Spatial Learning, Memory, Amyloid Precursor Protein and Seladin-1 Expression in the Hippocampus Of Streptozotocin-Exposed Rats
Author/Authors :
Mohseni Kouchesfahani Homa نويسنده Department of Zoology, School of Biological Sciences, Kharazmi University, Tehran, Iran , Zendedel Adib نويسنده Department of Anatomy, Tehran University of Medical Sciences, Tehran, IR Iran , Hassanzadeh Golamreza نويسنده Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran. , Beyer Cordian نويسنده Institute of Neuroanatomy, RWTH Aachen University, Aachen, Germany. , Elmizadeh Hamideh نويسنده , Fallahi Zahra نويسنده Department of Animal Biology - Faculty of Biological Science - Kharazmi University, Tehran , Khanmohammadi Mohammad نويسنده Department of Analytical Chemistry - Faculty of Chemistry, Imam Khomeini International University , Mahakizadeh Simin نويسنده Department of Anatomy - Faculty of Medicine - Tehran University of Medical Sciences, Tehran , Sharifzadeh Mohammad نويسنده Department of Pharmacology & Toxicology - Faculty of Pharmacy, Tehran University of medical sciences, Tehran , Nouri Kosar نويسنده Department of Animal Biology - Faculty of Biological Science - Kharazmi University, Tehran , Heydarian Zahra نويسنده Department of Animal Biology - Faculty of Biological Science - Kharazmi University, Tehran
Abstract :
Alzheimerʹs disease (AD) is a progressive neurodegenerative disease characterized by memory and cognitive dysfunction due to neuronal cell loss in higher brain centers. Senile plaques containing amyloid B (AB) are associated with this disease as well as a reduction in cholinergic neuron numbers. Tacrine is a reversible cholinesterase inhibitor in clinical use to treat moderate forms of AD. Chitosan nanoparticles represent an effective systemic delivery system for drugs. The application of tacrine-loaded chitosan nanoparticles has been shown to selectively increase tacrine concentrations in the brain tissue. In this study, we compared magnetic and non-magnetic tacrine-loaded chitosan nanoparticles for their bioactivity and neuroprotective potency in streptozotocin (stz)-induced neurodegeneration, an accepted animal model for AD. Male rats received a single injection of stz via an implanted cannula into the lateral brain ventricle. Tacrine (tac)-loaded chitosan nanoparticles were delivered into the tail vein. Spatial learning and memory were analyzed using the Morris water maze task. Amyloid precursor protein gene (APP) and seladin-1 gene expression were studied in the hippocampus by real time-PCR. Tac-loaded non-magnetic and tac-loaded magnetic chitosan nanoparticles improved spatial learning and memory after stz treatment with magnetic nanoparticles being most effective. Similarly, tac-loaded chitosan nanoparticles increased seladin-1 and reduced APP gene expression. Again, magnetic nanoparticles were more effective. These data reveal that tac-loaded non magnetic and tac-loaded magnetic chitosan nanoparticles to a higher extent improve brain deficits related to stz application. We conclude that the magnetic target drug delivery system is a promising therapeutic strategy to protect AD-related degenerating in the CNS
