Fingolimod (FTY720) improves postoperative cognitive dysfunction in mice subjected to D-galactose-induced aging

Area of Science:

• Neuroscience
• Pharmacology
• Gerontology

Background:

• Postoperative cognitive dysfunction (POCD) is a significant clinical challenge, particularly in elderly patients.
• Fingolimod (FTY720), a sphingosine-1-phosphate receptor modulator, exhibits neuroprotective properties in various central nervous system disease models.
• The potential of FTY720 to alleviate POCD remains largely unexplored.

Purpose of the Study:

• To investigate the efficacy of FTY720 in preventing neurocognitive impairment in a mouse model of D-galactose-induced aging.
• To assess the impact of FTY720 on spatial memory, problem-solving ability, and long-term memory following anesthesia and surgery.

Main Methods:

• An accelerated aging model was established using D-galactose administration in mice.
• Mice underwent partial hepatolobectomy under sevoflurane anesthesia.
• FTY720 was administered intraperitoneally before and after the surgical procedure.
• Neurocognitive function was evaluated using the Y-maze and puzzle box tests.
• Immunohistochemistry and Western blot assays were employed to assess microglial activation and synaptic protein expression in the hippocampus.

Main Results:

• Anesthesia and surgery led to significant spatial memory deficits in the Y-maze test.
• FTY720 treatment notably improved problem-solving and long-term memory in the puzzle box test.
• FTY720 significantly inhibited microglial activation in the hippocampal CA1 region.
• FTY720 down-regulated the expression of postsynaptic density protein 95 (PSD-95) and GluR2 in the hippocampus.

Conclusions:

• FTY720 demonstrates potential in ameliorating postoperative cognitive dysfunction in an aging mouse model.
• FTY720's neuroprotective effects may be mediated through the inhibition of neuroinflammation and modulation of synaptic protein expression.