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Fingolimod affects gene expression profile associated with LPS-induced memory impairment

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Abstract

Lipopolysaccharide is an endotoxin to induce sickness behavior in several animal models to explore the link between immune activation and cognition. Neuroinflammation playing a pivotal role in disease progress is evidently influenced by sphingosine-1-phosphate. As one of the sphingosine analogs in clinical use for multiple sclerosis, fingolimod (FTY720) was shown to substantially affect gene expression profile in the context of AD in our previous experiments. The present study was designed to evaluate the drug efficacy in the context of the mere inflammatory context leading to memory impairment. FTY720 was repeatedly administered for a few days before or after intracerebral lipopolysaccharide (LPS) injection in rats. Animal’s brains were then assigned to histological as well as multiplex mRNA assay following memory performance test. Both FTY720 pre-treatment and post-treatment were similarly capable of ameliorating LPS-induced memory impairment as assessed by passive avoidance test. Such amending effects may be partly accountable by the concomitant alterations in transcriptional levels of mitogen-activated protein kinases as well as inflammatory genes determined by QuantiGene Plex analysis. These findings confirming FTY720 application benefits suggest its efficacy may not differ significantly while considered either as a preventive or as a therapeutic approach against neuroinflammation.

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Acknowledgments

This research is funded by a HIR MoHE grant (J-200005-73849). The authors are very grateful to Prof. Abbas Kebriaeezadeh and Dr. Hamid Rezaei-Far for FTY720.

Conflict of interest

The authors declare no conflict of interest.

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Authors and Affiliations

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

    Rana Omidbakhsh, Zahurin Mohamed & Abolhassan Ahmadiani

  2. Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Banafshe Rajabli, Behzad Khallaghi & Abolhassan Ahmadiani

  3. Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Sanaz Nasoohi

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

    Murali Naidu

  5. NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

    Leila Dargahi

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  1. Rana Omidbakhsh
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  2. Banafshe Rajabli
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Correspondence to Leila Dargahi.

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Omidbakhsh, R., Rajabli, B., Nasoohi, S. et al. Fingolimod affects gene expression profile associated with LPS-induced memory impairment. Exp Brain Res 232, 3687–3696 (2014). https://doi.org/10.1007/s00221-014-4052-4

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  • DOI: https://doi.org/10.1007/s00221-014-4052-4

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