Plasma amyloid beta level changes in aged mice with cognitive dysfunction following sevoflurane exposure

Area of Science:

• Neuroscience
• Anesthesiology
• Gerontology

Background:

• Anesthetic-induced cognitive impairment is linked to amyloid beta (Aβ).
• Brain transport mechanisms for Aβ remain under-investigated.
• Receptor for advanced glycation end-products (RAGE) mediates Aβ influx; Low-density lipoprotein receptor-related protein-1 (LRP-1) mediates efflux.

Purpose of the Study:

• To investigate sevoflurane's effects on cognitive function, plasma Aβ levels, and Aβ transporters in aged mice.
• To elucidate the role of RAGE and LRP-1 in sevoflurane-induced cognitive changes.

Main Methods:

• Aged mice exposed to sevoflurane or control conditions.
• Spatial learning and memory assessed using the Morris water maze.
• Plasma Aβ concentrations measured via ELISA.
• Brain RAGE and LRP-1 gene and protein expression analyzed using qPCR and Western blot; RAGE localization confirmed by immunofluorescence.

Main Results:

• Sevoflurane exposure increased escape latency and decreased time in the target quadrant, indicating cognitive impairment.
• Sevoflurane reduced plasma Aβ1-40 levels.
• Sevoflurane increased RAGE gene and protein expression in the brain, with RAGE co-localizing to hippocampal vascular endothelial cells.

Conclusions:

• Sevoflurane-induced cognitive dysfunction in aged mice is associated with increased RAGE expression.
• Over-expression of RAGE in hippocampal vasculature may facilitate excessive Aβ1-40 transport into the brain.
• RAGE-mediated Aβ transport is a potential mechanism underlying anesthetic-induced cognitive impairment.