Bibliographic
This study investigated effects of sphingosine-1-phosphate receptor modulator FTY720 on neuroprotection and memory in a rat model of AD. AD is highly associated with deregulation of lysophospholipids (LPs) of which one of the best known is sphingosine-1-phosphate. LPs can play multiple roles in relevance to CNS disorders, especially those associated with CNS injuries and inflammation, including memory impairment and neurological disorders like AD. Past studies have shown the anti-inflammatory and protective effect of FTY720 in some neurodegenerative disorders like ischemia, and chronic administration prevents impairment of spatial learning and memory in AD rats. Here FTY720 was examined on AD rats in comparison to the only clinically approved NMDA receptor antagonist-memantine. Passive avoidance task showed significant memory restoration in AD animals received FTY720 comparable to memantine. Upon gene profiling by QuantiGene Plex, this behavioral outcomes was concurrent with considerable alterations in some genes transcripts like that of mitogen activated protein kinases (MAPKs) and some inflammatory markers that may particularly account for the detected decline in hippocampal neural damage or memory impairment associated with AD. From a therapeutic standpoint, these findings conclude that FTY720 may suggest new opportunities for AD management probably based on several modulatory effects on genes involved in cell death or survival.
Therapeutic Agent
Fingolimod is FDA-approved to treat patients with the relapsing-remitting form of multiple sclerosis (MS).
Animal Model
Experimental Design
In studies using rats, typically the rat weight is reported rather than age. A male Sprague Dawley rat weighing 200-250g is between 6-8 weeks old. A female Sprague Dawley rat weighing 200-250g is between 8-10 weeks old (https://www.taconic.com/pdfs/sprague-dawley-rat.pdf).