Abstract
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-CamKIIα, 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.
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Yuan-Lin Wang and Feng Li have equally contributed to this work.
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Wang, YL., Li, F. & Chen, X. Pten Inhibitor-bpV Ameliorates Early Postnatal Propofol Exposure-Induced Memory Deficit and Impairment of Hippocampal LTP. Neurochem Res 40, 1593–1599 (2015). https://doi.org/10.1007/s11064-015-1633-y
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DOI: https://doi.org/10.1007/s11064-015-1633-y