title: Inhibition of PARP-1 participates in the mechanisms of propofol-induced amnesia in mice and human.
abstract: Poly(ADP-ribose) polymerase 1 (PARP-1) has emerged as an important regulator in learning and memory. Propofol leads to amnesia, however, the mechanism remains unclear. The present study was designed to examine whether and how PARP-1 plays a role in propofol-induced amnesia. Mice were injected intraperitoneally with propofol before acquisition training. Cognitive function was evaluated by object recognition test. PARP-1 and PAR expression was determined through Western blot. The protein and mRNA levels of Arc and c-Fos were detected by Western blot and real-time PCR. Thirty volunteers were assigned to three groups according to codon 762 variation of PARP-1 gene (rs1136410). They learned word lists awake and during propofol sedation. Their cognitive traits were evaluated through fMRI. Rodent data demonstrated that propofol inhibited acquisition-induced increase in PARP-1 and PAR, thereby suppressing Arc and c-Fos, which impaired object recognition 24h after learning. Consistent with this, carriers of a low-catalyzing function PARP-1 variant (Val762Ala) exhibited decreased retrieval-induced hippocampal reactivity 24h after learning under propofol-sedative condition. These findings suggested that inhibition of PARP-1 might participate in the mechanism of propofol-induced amnesia in mice and human. More generally, our approach illustrated a potential translational research bridging animal models and human studies.
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Jia
authors.affiliation: Department of Anesthesiology, Zhejiang Provincial People׳s Hospital, 158 Shangtang Road, Hangzhou 310014, China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Fujun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Han
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China.
authors.forename: Qingsheng
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai 200025, China. Electronic address: buwei_yu@163.com.
authors.forename: Buwei
authors.initials: B
authors.lastname: Yu
mesh_terms: D000328:Adult; D000647:Amnesia / Q000139:chemically induced / Q000378:metabolism*; D000818:Animals; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008297:Male; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000494:pharmacology; D015742:Propofol / Q000494:pharmacology*
chemical_list: D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D000071137:Poly (ADP-Ribose) Polymerase-1; D015742:Propofol
keywords: Amnesia; Hippocampus; Poly(ADP-ribose) polymerase 1; Propofol