Dendrobine attenuates postoperative cognitive dysfunction by inhibiting Runx1-mediated NF-κB signaling pathway

Area of Science:

• Neuroscience
• Pharmacology
• Gerontology

Background:

• Postoperative cognitive dysfunction (POCD) in older adults is linked to neuroinflammation via microglial activation and NF-κB signaling.
• Runx1 is an upstream regulator of NF-κB, but its role in POCD is not understood.
• Dendrobine, from Dendrobium species, has known anti-inflammatory and neuroprotective properties.

Purpose of the Study:

• To investigate the role of Runx1 in POCD.
• To evaluate the therapeutic potential of dendrobine in ameliorating POCD.
• To elucidate the underlying molecular mechanisms of dendrobine's effects on neuroinflammation and neuronal survival.

Main Methods:

• POCD was induced in aged mice using sevoflurane anesthesia and surgery.
• Cognitive function was assessed using behavioral tests (Morris Water Maze, Novel Object Recognition).
• Molecular analyses included RNA sequencing, Western blotting, immunofluorescence, and in vitro cell cultures to examine inflammatory pathways, apoptosis, and synaptic plasticity. Runx1's function was tested via knockdown and overexpression.

Main Results:

• Dendrobine administration improved memory and reduced neuroinflammation, microglial activation, and neuronal apoptosis in POCD mice.
• Dendrobine suppressed NF-κB signaling by downregulating Runx1 expression, identified as an upstream modulator.
• Runx1 inhibition potentiated dendrobine's anti-inflammatory effects, while Runx1 overexpression diminished them.

Conclusions:

• Dendrobine effectively ameliorates POCD by inhibiting the Runx1/NF-κB pathway, thereby reducing neuroinflammation and neuronal apoptosis.
• Runx1 acts as a critical upstream mediator of NF-κB signaling in the context of POCD.
• Targeting the Runx1/NF-κB axis presents a promising therapeutic strategy for perioperative neuroprotection.