Pten Inhibitor-bpV Ameliorates Early Postnatal Propofol Exposure-Induced Memory Deficit and Impairment of Hippocampal LTP

Early postnatal propofol administration has potential detrimental effects on hippocampal synaptic development and memory. Therapeutic method is still lack due to unknown mechanisms. In this study, a 7-day propofol protocol was applied to model anesthesia in neonatal mice. Phosphatase and tensin homolog deleted on chromosome ten (Pten) inhibitor bisperoxovanadium (bpV) was pre-applied before propofol to study its potential protection. After propofol application, Pten level increased while phospho-AKT (p-AKT) (Ser473) decreased in dorsal hippocampus. Interestingly, i.p. injection of Pten inhibitor reversed the decrease of p-AKT. Two months after administration, basal synaptic transmission, hippocampal long-term potentiation (LTP) and long-term memory were reduced in propofol-administrated mice. By contrast, i.p. injection of Pten inhibitor at a dose of 0.2 mg/kg/day before propofol reversed the detrimental effects due to propofol application. Consistently, bpV injection also reversed propofol application-induced decrease of synaptic plasticity-related proteins, including p-CamKII alpha, p-PKA and postsynaptic density protein 95. Taken together, our results demonstrate that bpV injection could reverse early propofol exposure-induced decrease of memory and hippocampal LTP. bpV might be a potential therapeutic for memory impairment after early propofol postnatal application.