Metformin activates the PI3K/AKT/BDNF axis to attenuate postoperative cognitive dysfunction

Area of Science:

• Neuroscience
• Pharmacology
• Anesthesiology

Background:

• Postoperative cognitive dysfunction (POCD) is a common complication following anesthesia and surgery.
• Metformin, an antidiabetic medication, exhibits neuroprotective effects and can improve cognitive deficits.
• The precise mechanisms by which metformin ameliorates POCD are not fully understood.

Purpose of the Study:

• To investigate the efficacy of metformin in an in vivo model of POCD.
• To elucidate the underlying molecular mechanisms of metformin's neuroprotective effects in POCD.

Main Methods:

• An in vivo POCD model was established using isoflurane anesthesia and exploratory laparotomy in mice.
• Cognitive function, anxiety-like behaviors, synaptic plasticity, neuroinflammation, and neuronal apoptosis were assessed.
• The PI3K/AKT/BDNF signaling pathway was analyzed in vitro and in vivo.

Main Results:

• Metformin pretreatment significantly improved cognitive function and reduced anxiety-like behaviors in POCD mice.
• Metformin restored synaptic plasticity, normalized synaptic protein levels, and increased dendritic density in the hippocampus.
• Metformin attenuated neuroinflammation, reduced neuronal apoptosis, and activated the PI3K/AKT/BDNF pathway.

Conclusions:

• Metformin effectively alleviates POCD in a mouse model.
• The neuroprotective effects of metformin involve modulating the PI3K/AKT/BDNF signaling pathway.
• Metformin presents a promising therapeutic strategy for preventing and treating POCD.