title: Detrimental effects of postnatal exposure to propofol on memory and hippocampal LTP in mice.
abstract: Acute effects of propofol on memory and hippocampal long-term potentiation (LTP) in adult animals were reported. However, long-term effect of early postnatal application of propofol on memory was not totally disclosed. In this study, experiments were designed to verify the mechanisms underlying the long-term detrimental effects of propofol on memory and hippocampal synaptic plasticity. A consecutive propofol protocol from postnatal day 7 was applied to model anesthesia, long term memory and hippocampal synaptic plasticity were detected 2 months later. Our results showed that repeated propofol exposure in early phase affect the memory in the adult phase. Through recording the field excitatory postsynaptic potentials (fEPSPs) at Schaffer colletaral-CA1 synapses, both of basal synaptic transmission and hippocampal LTP were decreased after propofol application. While LTD induced by low frequency stimulation and 3,5-dihydroxyphenylglycine (3,5-DHPG) were not affected. Through analyzing the ultrastructure of dendrite in CA1 region, we found that propofol application decreased the spine density, which was consistent with the decrease of PSD-95 expression. In addition, p-AKT level was reduced after first propofol application. Intracerebroventricular injection of Akt inhibitor could mimic the propofol effects on basal synaptic transmission, hippocampal LTP and memory. Taken together, these results suggested that propofol possibly decreased AKT signaling pathway to restrict the spine development, finally leading to hippocampal LTP impairment and memory deficit.
authors.affiliation: Department of Anesthesiology, Huai׳an First People׳s Hospital, Nanjing Medical University, Huai׳an, Jiangsu 223300, China.
authors.forename: Yuan-Lin
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Huai׳an First People׳s Hospital, Nanjing Medical University, Huai׳an, Jiangsu 223300, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Wuxi People׳s Hospital, Affiliated Hospital of Nanjing Medical University, Wuxi 214023, China. Electronic address: zhpsqxt@163.com.
authors.forename: Zhi-Ping
authors.initials: ZP
authors.lastname: Wang
mesh_terms: D018686:Anesthetics, Intravenous / Q000633:toxicity*; D000818:Animals; D000831:Animals, Newborn; D002867:Chromones / Q000494:pharmacology; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D000076122:Disks Large Homolog 4 Protein; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D051528:Guanylate Kinases / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D008810:Mice, Inbred C57BL; D009025:Morpholines / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000633:toxicity*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors / Q000378:metabolism; D012118:Resorcinols / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D046509:Tissue Culture Techniques
chemical_list: D018686:Anesthetics, Intravenous; D002867:Chromones; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D004791:Enzyme Inhibitors; D018683:Excitatory Amino Acid Agents; D008565:Membrane Proteins; D009025:Morpholines; D012118:Resorcinols; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C079215:3,5-dihydroxyphenylglycine; D051057:Proto-Oncogene Proteins c-akt; D051528:Guanylate Kinases; D005998:Glycine; D015742:Propofol
keywords: Long-term potentiation; Memory; Propofol; Synaptic spines