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.
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Authors | Lijie Jia, Wenyuan Wang, Yan Luo, Fujun Zhang, Han Lu, Qingsheng Xue, Buwei Yu |
Journal | Brain research
(Brain Res)
Vol. 1637
Pg. 137-145
(Apr 15 2016)
ISSN: 1872-6240 [Electronic] Netherlands |
PMID | 26921778
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2016 Elsevier B.V. All rights reserved. |
Chemical References |
- Poly(ADP-ribose) Polymerase Inhibitors
- Poly (ADP-Ribose) Polymerase-1
- Propofol
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Topics |
- Adult
- Amnesia
(chemically induced, metabolism)
- Animals
- Hippocampus
(drug effects, metabolism)
- Humans
- Male
- Memory
(drug effects)
- Mice
- Mice, Inbred C57BL
- Poly (ADP-Ribose) Polymerase-1
(antagonists & inhibitors, genetics, metabolism)
- Poly(ADP-ribose) Polymerase Inhibitors
(pharmacology)
- Propofol
(pharmacology)
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