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: Masoumeh Asle-Rousta, Zeynab Kolahdooz, Shahrbanoo Oryan, Abolhassan Ahmadiani, Leila Dargahi
• Journal: Journal of molecular neuroscience : MN (J Mol Neurosci) Vol. 50 Issue 3 Pg. 524-32 (Jul 2013) ISSN: 1559-1166 [Electronic] United States
• PMID: 23435938 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Peptide Fragments
• Propylene Glycols
• amyloid beta-protein (1-42)
• Fingolimod Hydrochloride
• Sphingosine

Topics

• Amyloid beta-Peptides (toxicity)
• Animals
• Apoptosis (drug effects)
• Fingolimod Hydrochloride
• Hippocampus (pathology)
• Male
• Maze Learning (drug effects)
• Memory (drug effects)
• Memory Disorders (chemically induced, drug therapy)
• Peptide Fragments (toxicity)
• Propylene Glycols (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Sphingosine (analogs & derivatives, pharmacology, therapeutic use)