Inhibition of PARP-1 participates in the mechanisms of propofol-induced amnesia in mice and human
| Autor: | Wen-Yuan Wang, Qingsheng Xue, Li-Jie Jia, Han Lu, Fujun Zhang, Buwei Yu, Yan Luo |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Adult
Male 0301 basic medicine MAPK/ERK pathway Poly (ADP-Ribose) Polymerase-1 Regulator Amnesia Hippocampus Poly(ADP-ribose) Polymerase Inhibitors Hippocampal formation Mice 03 medical and health sciences 0302 clinical medicine Western blot Memory medicine Animals Humans Propofol Molecular Biology Arc (protein) medicine.diagnostic_test business.industry General Neuroscience Mice Inbred C57BL 030104 developmental biology Neurology (clinical) medicine.symptom business Neuroscience 030217 neurology & neurosurgery Developmental Biology medicine.drug |
| Zdroj: | Brain Research. 1637:137-145 |
| ISSN: | 0006-8993 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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