title: Fingolimod affects gene expression profile associated with LPS-induced memory impairment.
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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Malaya, 50603, Kuala Lumpur, Malaysia.
authors.forename: Rana
authors.initials: R
authors.lastname: Omidbakhsh
authors.forename: Banafshe
authors.initials: B
authors.lastname: Rajabli
authors.forename: Sanaz
authors.initials: S
authors.lastname: Nasoohi
authors.forename: Behzad
authors.initials: B
authors.lastname: Khallaghi
authors.forename: Zahurin
authors.initials: Z
authors.lastname: Mohamed
authors.forename: Murali
authors.initials: M
authors.lastname: Naidu
authors.forename: Abolhassan
authors.initials: A
authors.lastname: Ahmadiani
authors.forename: Leila
authors.initials: L
authors.lastname: Dargahi
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D003623:Dark Adaptation / Q000187:drug effects; D004195:Disease Models, Animal; D004333:Drug Administration Routes; D004334:Drug Administration Schedule; D005260:Female; D000068876:Fingolimod Hydrochloride; D005786:Gene Expression Regulation / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011409:Propylene Glycols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D059467:Transcriptome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D007166:Immunosuppressive Agents; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D009419:Nerve Tissue Proteins; D011409:Propylene Glycols; D014409:Tumor Necrosis Factor-alpha; D053148:Caspase 3; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine
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