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Title: Neuron-restrictive silencer factor is not required for the antiepileptic effect of the ketogenic diet
Author: Hu, Xiao-Ling ; Cheng, Xuewen ; Fei, Jian ; null(熊志奇)
Source: EPILEPSIA
Issued Date: 2011
Volume: 52, Issue:9, Pages:1609-1616
Keyword: Neuron-restrictive silencer factor ; Ketogenic diet ; 2-Deoxy-D-glucose ; Acetone ; Epilepsy ; Kindling ; TRANSCRIPTIONAL REPRESSION ; LIMBIC EPILEPTOGENESIS ; GLYCOLYSIS INHIBITION ; GENE-EXPRESSION ; IN-VIVO ; ANTICONVULSANT ; REST ; EPILEPSY ; ACETONE ; METABOLISM
Subject: Neurosciences & Neurology
Corresponding Author: Fei, J (reprint author), Tongji Univ, Sch Life Sci & Technol, 1239 Siping Rd, Shanghai 200092, Peoples R China,Jfei@mail.tongji.edu.cn ; xiongzhiqi@ion.ac.cn
English Abstract: Purpose: The ketogenic diet (KD) has been used as an effective antiepileptic treatment for nearly a century. Inhibition of glycolysis and increased levels of ketone bodies are both known to contribute to the antiepileptic effects of the KD. Neuron-restrictive silencer factor (NRSF), also known as RE-1 silencing transcription factor (REST), is implicated in the antiepileptic effects of the glycolytic inhibitor 2-deoxy-D-glucose (2DG). Glycolytic inhibition is a common feature of the KD and 2DG treatment, leading to the hypothesis that NRSF might also be involved in the antiepileptic effect of the KD. To test this hypothesis, the present study was designed to investigate the role of NRSF in the antiepileptic effect of 2DG, the KD, and acetone in vivo. Methods: Kindling was used as a model to test the antiepileptic effects of 2DG, the KD, and acetone on control and NRSF conditional knockout mice (NRSF-cKO; from the intercross of CamKIIa-iCre and NRSF exon 2 floxed mice). After recovery from electrode implantation, adult mice were stimulated twice a day at afterdischarge threshold (ADT) current intensity. In the 2DG- (500 mg/kg) and acetone-(10 mmol/kg) treated groups, drugs were injected intraperitoneally 20 min before each stimulus. In the 2DG group, mice were pretreated with intraperitoneal injections for 3 days in addition to the injections administered before the regular kindling stimulation. In the KD group, mice were fed the KD instead of a control diet until the end of stimulations. Key Findings: Compared with control mice, the antiepileptic effect of 2DG was abolished in NRSF-cKO mice, indicating that NRSF is required for the antiepileptic effect of 2DG. In the KD-fed group, kindling development was retarded in both control and NRSF-cKO mice. In the acetone-treated group, inhibition of kindling-induced epileptogenesis was observed in both control and NRSF-cKO mice, similar to the action of the KD. Significance: These findings imply that NRSF repression complex is not essential for the antiepileptic effect of the ketogenic diet.
Indexed Type: sci
Language: 英语
Content Type: 期刊论文
URI: http://ir.sibs.ac.cn/handle/331001/1528
Appears in Collections:神经所(总)_期刊论文
疾病神经生物学研究组_期刊论文

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Hu, Xiao-Ling; Cheng, Xuewen; Fei, Jian; Xiong, Zhi-Qi.Neuron-restrictive silencer factor is not required for the antiepileptic effect of the ketogenic diet,EPILEPSIA,2011,52(9):1609-1616
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