FGF19 improves sevoflurane-induced cognitive dysfunction in rats through the PGC-1α/BDNF/FNDC5 pathway

Area of Science:

• Neuroscience
• Pharmacology
• Molecular Biology

Background:

• Postoperative cognitive dysfunction (POCD) is a significant central nervous system complication impacting memory, information processing, and emotional well-being.
• Fibroblast growth factor 19 (FGF19) has emerged as a potential therapeutic agent in neurological diseases, but its role in POCD is yet to be elucidated.
• Understanding the mechanisms by which FGF19 influences POCD is crucial for developing targeted interventions.

Purpose of the Study:

• To investigate the therapeutic effect of FGF19 on sevoflurane-induced POCD in a rat model.
• To explore the underlying molecular mechanisms, including anti-neuroinflammatory and anti-oxidative stress effects of FGF19 in POCD.
• To identify the specific signaling pathway modulated by FGF19 in improving POCD symptoms.

Main Methods:

• Rats were subjected to sevoflurane anesthesia and treated with AAV-empty or AAV-FGF19.
• Cognitive function was assessed using the Morris water maze (MWM) test.
• Neuroinflammation markers (TNF-α, IL-6, IL-1β, IL-10), oxidative stress (DHE staining), neuronal injury (NISSL, TUNEL assays), and the PGC-1α/BDNF/FNDC5 pathway were analyzed.

Main Results:

• FGF19 administration significantly improved cognitive deficits in rats exposed to sevoflurane.
• FGF19 demonstrated anti-neuroinflammatory and anti-oxidative stress effects, reducing markers of inflammation and oxidative damage.
• FGF19 treatment alleviated sevoflurane-induced hippocampal neuron injury and modulated the PGC-1α/BDNF/FNDC5 signaling pathway.

Conclusions:

• FGF19 effectively ameliorates sevoflurane-induced POCD in rats, highlighting its therapeutic potential.
• The protective effects of FGF19 are mediated through the suppression of neuroinflammation, oxidative stress, and neuronal apoptosis.
• FGF19 exerts its beneficial effects by activating the PGC-1α/BDNF/FNDC5 pathway, offering a novel therapeutic target for POCD.