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Protective Effect of a cAMP Analogue on Behavioral Deficits and Neuropathological Changes in Cuprizone Model of Demyelination

Vakilzadeh, G. and Khodagholi, F. and Ghadiri, T. and Darvishi, M. and Ghaemi, A. and Noorbakhsh, F. and Gorji, A. and Sharifzadeh, M. (2014) Protective Effect of a cAMP Analogue on Behavioral Deficits and Neuropathological Changes in Cuprizone Model of Demyelination. Molecular Neurobiology. ISSN 08937648 (ISSN) (In Press)

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Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease that leads to neuronal cell loss. Cyclic AMP and its analogs are well known to decrease inflammation and apoptosis. In the present study, we examined the effects of bucladesine, a cell-permeable analogue of cyclic adenosine monophosphate (cAMP), on myelin proteins (PLP, PMP-22), inflammation, and apoptotic, as well as anti-apoptotic factors in cuprizone model of demyelination. C57BL/6J mice were fed with chow containing 0.2 % copper chelator cuprizone or vehicle by daily oral gavage for 5 weeks to induce reversible demyelination predominantly of the corpus callosum. Bucladesine was administered intraperitoneally at different doses (0.24, 0.48, or 0.7 μg/kg body weight) during the last 7 days of 5-week cuprizone treatment. Bucladesine exhibited a protective effect on myelination. Furthermore, bucladesine significantly decreased the production of interleukin-6 pro-inflammatory mediator as well as nuclear factor-κB activation and reduced the mean number of apoptotic cells compared to cuprizone-treated mice. Bucladesine also decreased production of caspase-3 as well as Bax and increased Bcl-2 levels. Our data revealed that enhancement of intracellular cAMP prevents demyelination and plays anti-inflammatory and anti-apoptotic properties in mice cuprizone model of demyelination. This suggests the modulation of intracellular cAMP as a potential target for treatment of MS. © 2014 Springer Science+Business Media New York.

Item Type: Article
Additional Information: Unmapped bibliographic data: LA - English [Field not mapped to EPrints] J2 - Mol. Neurobiol. [Field not mapped to EPrints] AD - School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran [Field not mapped to EPrints] AD - Shefa Neuroscience Research Center, Tehran, Iran [Field not mapped to EPrints] AD - Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran [Field not mapped to EPrints] AD - Infectious Diseases Research Center, Department of Microbiology, School of Medicine, Golestan University of Medical Sciences, Gorgan, Iran [Field not mapped to EPrints] AD - Department of Immunology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran [Field not mapped to EPrints] AD - Institut für Physiologie I, Klinik und Poliklinik für Neurochirurgie, Department of Neurology, Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster, Germany [Field not mapped to EPrints] AD - Department of Pharmacology and Toxicology, Pharmaceutical Sciences research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, P.O. Box 14155-6451, Tehran, Iran [Field not mapped to EPrints] AD - Epilepsy Research Center, Universität Münster, Robert-Koch-Strasse 27a, Münster, D-48149, Germany [Field not mapped to EPrints] DB - Scopus [Field not mapped to EPrints]
Uncontrolled Keywords: Apoptosis, Cell death, Cuprizone, Demyelination, Neuroinflammation, Pathogenesis
Subjects: مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 19 Apr 2015 05:34
Last Modified: 20 Jun 2015 04:54
URI: http://eprints.goums.ac.ir/id/eprint/1685

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