title: FTY720 (fingolimod) attenuates beta-amyloid peptide (Aβ42)-induced impairment of spatial learning and memory in rats.
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 (Aβ(42)) 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 Aβ(42)-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 Aβ(42)-induced neurotoxicity and also suggest that S1P receptors and signaling pathways may provide a potential target for the treatment of AD.
authors: Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Evin, Tehran, 19615-1178, Iran.
authors: Masoumeh
authors: M
authors: Asle-Rousta
authors: Zeynab
authors: Z
authors: Kolahdooz
authors: Shahrbanoo
authors: S
authors: Oryan
authors: Abolhassan
authors: A
authors: Ahmadiani
authors: Leila
authors: L
authors: Dargahi
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000068876:Fingolimod Hydrochloride; D006624:Hippocampus / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects*; D008568:Memory / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000188:drug therapy*; D010446:Peptide Fragments / Q000633:toxicity*; D011409:Propylene Glycols / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011409:Propylene Glycols; C075222:amyloid beta-protein (1-42); D000068876:Fingolimod Hydrochloride; D013110:Sphingosine