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FTY720 (Fingolimod) Attenuates Beta-amyloid Peptide (Aβ42)-Induced Impairment of Spatial Learning and Memory in Rats

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Abstract

Imbalanced lipid metabolism and increase in the ceramide-to-S1P ratio in the brain have been postulated to play a role in amyloidogenesis, neuroinflammatory reactions, and neuronal apoptosis in Alzheimer’s disease (AD) pathology. FTY720, the immunomodulatory sphingosine 1-phosphate (S1P) analog, has recently gained interest because of its CNS-directed effects. In addition to its immunomodulatory functions in multiple sclerosis, FTY720 possesses anti-inflammatory and neuroprotective roles in different cerebral ischemia models. In the present study, we examined the effects of FTY720 in a rat model of AD. Memory deficit was induced by bilateral intrahippocampus injection of beta-amyloid peptide (Aβ42) and examined through the Morris water maze test. The extent of histological injury in the hippocampus and the activation of caspase-3 were determined respectively by Nissl staining and Western blotting. Chronic daily administration of FTY720 (1 mg/kg, i.p., 14 days) significantly attenuated the Aβ42-induced learning and memory impairment and prevented the hippocampus neuronal damage as well as caspase-3 activation. These data show for the first time that FTY720 has a beneficial effect in restoring memory loss in Aβ42-induced neurotoxicity and also suggest that S1P receptors and signaling pathways may provide a potential target for the treatment of AD.

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Acknowledgments

This study was supported financially by the Neuroscience Research Center of the Shahid Beheshti University of Medical Sciences. The authors are thankful to Prof. Abbas Kebriaeezadeh and Dr. Hamid Rezaei-Far for FTY720.

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Authors and Affiliations

  1. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Evin, Tehran, 19615-1178, Iran

    Masoumeh Asle-Rousta, Zeynab Kolahdooz, Abolhassan Ahmadiani & Leila Dargahi

  2. Department of Biology, Faculty of Basic and Medical Sciences, Zanjan Branch, Islamic Azad University, Zanjan, Iran

    Masoumeh Asle-Rousta

  3. Faculty of Biological Sciences, Kharazmi University, Tehran, Iran

    Shahrbanoo Oryan

  4. Department of Pharmacology, Faculty of Medicine, University of Malaya, Kuala Lumpur, 50603, Malaysia

    Abolhassan Ahmadiani

Authors
  1. Masoumeh Asle-Rousta
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  2. Zeynab Kolahdooz
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  3. Shahrbanoo Oryan
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  4. Abolhassan Ahmadiani
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  5. Leila Dargahi
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Corresponding author

Correspondence to Leila Dargahi.

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Masoumeh Asle-Rousta and Zeynab Kolahdooz contributed equally to this work.

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Asle-Rousta, M., Kolahdooz, Z., Oryan, S. et al. FTY720 (Fingolimod) Attenuates Beta-amyloid Peptide (Aβ42)-Induced Impairment of Spatial Learning and Memory in Rats. J Mol Neurosci 50, 524–532 (2013). https://doi.org/10.1007/s12031-013-9979-6

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  • DOI: https://doi.org/10.1007/s12031-013-9979-6

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