Rutin ameliorates sevoflurane-induced neurotoxicity by inhibiting microglial synaptic phagocytosis through the...

Area of Science:

• Neuroscience
• Developmental Biology
• Pharmacology

Background:

• Neonatal exposure to sevoflurane can cause synaptic impairment and neurodevelopmental issues.
• Microglial synaptic elimination, mediated by the complement cascade, plays a role in this neurotoxicity.

Purpose of the Study:

• To investigate the therapeutic potential of rutin in mitigating sevoflurane-induced neurotoxicity.
• To elucidate the mechanisms by which rutin affects microglial activation and synaptic pruning.

Main Methods:

• Mice were exposed to sevoflurane on postnatal days 6, 8, and 10.
• Cognitive function and anxiety-like behaviors were assessed using the Morris water maze and open field test.
• Hippocampal tissue was analyzed using Western blotting, RT-qPCR, and immunohistochemistry to examine complement cascade and microglial activity.

Main Results:

• Rutin treatment significantly alleviated cognitive dysfunction and synaptic impairment in mice exposed to sevoflurane.
• Rutin reduced microglial activation, shifting them from an ameboid to a ramified phenotype, and decreased their phagocytic activity.
• Rutin prevented synapse loss by inhibiting complement C1q and C3-mediated microglial engulfment, an effect reversible with C3 supplementation.

Conclusions:

• Rutin effectively counteracts sevoflurane-induced synapse loss and cognitive deficits.
• The mechanism involves inhibiting complement-dependent microglial phagocytosis of synapses.
• Rutin presents a promising therapeutic approach for preventing sevoflurane-induced developmental neurotoxicity.