Effects of NK-4 in a transgenic mouse model of Alzheimer's disease
| Autor: | Shigeharu Fukuda, Shigeyuki Arai, Tsunetaka Ohta, Hitomi Ohta, Kenji Akita |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Genetically modified mouse
Male Amyloid medicine.medical_treatment Intraperitoneal injection Drug Evaluation Preclinical lcsh:Medicine Mice Transgenic Water maze Pharmacology Toxicology PC12 Cells Pathogenesis Mice In vivo Alzheimer Disease medicine Animals lcsh:Science Maze Learning Biology Swimming Mice Inbred ICR Multidisciplinary Photosensitizing Agents business.industry lcsh:R Recognition Psychology Carbocyanines In vitro Rats Disease Models Animal Neurology Toxicity Quinolines Medicine lcsh:Q Female Dementia business Central Nervous System Agents Research Article |
| Zdroj: | PLoS ONE PLoS ONE, Vol 7, Iss 1, p e30007 (2012) |
| ISSN: | 1932-6203 |
| Popis: | Beta-amyloid (Aβ) peptides are considered to play a major role in the pathogenesis of Alzheimer's disease (AD) and molecules that can prevent pathways of Aβ toxicity may be potential therapeutic agents for treatment of AD. We have previously reported that NK-4, a cyanine photosensitizing dye, displays neurotrophic and antioxidant activities. In this study, we report the effects of NK-4 on the toxicity of Aβ and on cognitive function and Aβ concentration in a transgenic mouse model of AD (Tg2576). In vitro, NK-4 effectively protected neuronal cells from toxicity induced by Aβ. In addition, it displayed profound inhibitory activities on Aβ fibril formation. In vivo, Tg2576 mice received an intraperitoneal injection at 100 or 500 µg/kg of NK-4 once a day, five times a week for 9 months. Administration of NK-4 to the mice attenuated impairment of recognition memory, associative memory, and learning ability, as assessed by a novel object recognition test, a passive avoidance test, and a water maze test, respectively. NK-4 decreased the brain Aβ concentration while increasing the plasma amyloid level in a dose-dependent manner. NK-4 also improved memory impairments of ICR mice induced by direct intracerebroventricular administration of Aβ. These lines of evidence suggest that NK-4 may affect multiple pathways of amyloid pathogenesis and could be useful for treatment of AD. |
| Databáze: | OpenAIRE |
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