Neonatal propofol exposure impairs synaptic plasticity and cognition, associated with BAG3 upregulation and disrupted synaptic protein homeostasis.

BACKGROUND

Propofol is widely used in pediatric anesthesia, but it has been implicated in adverse effects on brain development following repeated early-life exposure. Bag3, a co-chaperone protein involved in proteostasis and the neuronal stress response, may play a critical role in regulating synaptic function during early brain maturation.

METHODS

Neonatal mice were treated with propofol on postnatal days 5-7. Hippocampal neurogenesis was assessed via BrdU immunofluorescence. Synaptic proteins (PSD95, SNAP25) and Bag3 expression were measured by Western blotting. Behavioral performance in adolescence was evaluated using open-field, elevated plus-maze, Morris water maze, Y-maze, and T-maze tests.

RESULTS

Propofol exposure significantly reduced proliferative activity (BrdU incorporation) in the dentate gyrus and decreased PSD95 and SNAP25 expression in both the cortex and hippocampus. Bag3 expression was markedly upregulated, accompanied by a mild increase in its phosphorylated form. Behaviorally, propofol-treated mice showed anxiety-like behavior and impairments in spatial learning and working memory.

CONCLUSION

These findings suggest that early-life exposure to propofol impairs neurogenesis and synaptic plasticity. This process is temporally associated with the upregulation of stress-responsive co-chaperone BAG3, which precedes the of synaptic protein homeostasis. While causal relationship remains to be established, these findings identifies BAG3 as a candidate correlative marker of anesthetic-induced neurotoxicity and highlights it as a target for future mechanistic studies.