Dataset Information

Nicotinamide adenine dinucleotide suppresses epileptogenesis at an early stage.

ABSTRACT: The pathophysiologic mechanisms of epileptogenesis are poorly understood, and no effective therapy exists for suppressing epileptogenesis. Numerous reports have shown that nicotinamide adenine dinucleotide (NAD⁺) has neuroprotective effects, suggesting its potential use for treating epileptogenesis. Here we evaluated the effects of NAD⁺ on epileptogenesis and the mechanisms underlying these effects. In pilocarpine-induced status epilepticus (SE) model mice, NAD⁺ was injected three times within 24.5?h after SE. NAD⁺ intervention significantly reduced the incidence of spontaneous recurrent seizure (SRS) and abnormal electroencephalogram (EEG) activity, rescued contextual fear memory formation, reduced neuronal loss in the CA1 region of the hippocampus at SRS stage. Furthermore, exogenous supply of NAD⁺ distinctly reversed the seizure-induced depletion of endogenous NAD⁺, reduced neuronal apoptosis in the CA1 region of the hippocampus, and reversed the augmented Acp53/p53 ratio at the early stage of epileptogenesis. Our findings demonstrated that early-stage intervention with NAD⁺ prevents epileptogenesis in pilocarpine-induced SE mice by suppressing neuronal apoptosis.

SUBMITTER: Liu J

PROVIDER: S-EPMC5544671 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Nicotinamide adenine dinucleotide suppresses epileptogenesis at an early stage.

Liu Juan J Yang Beimeng B Zhou Pei P Kong Yingying Y Hu Weiwei W Zhu Geng G Ying Weihai W Li Weidong W Wang Yun Y Li Shengtian S

Scientific reports 20170804 1

The pathophysiologic mechanisms of epileptogenesis are poorly understood, and no effective therapy exists for suppressing epileptogenesis. Numerous reports have shown that nicotinamide adenine dinucleotide (NAD+) has neuroprotective effects, suggesting its potential use for treating epileptogenesis. Here we evaluated the effects of NAD+ on epileptogenesis and the mechanisms underlying these effects. In pilocarpine-induced status epilepticus (SE) model mice, NAD+ ...[more]

PMID: 28779137

Similar Datasets

Project description:AimsAccurate analysis of dinucleotide redox cofactors nicotinamide adenine dinucleotide phosphate reduced (NADPH), nicotinamide adenine dinucleotide phosphate (NADP+), nicotinamide adenine dinucleotide reduced (NADH), and nicotinamide adenine dinucleotide (NAD+) from biological samples is important to understanding cellular redox homeostasis. In this study, we aimed to develop a simple protocol for quenching metabolism and extracting NADPH that avoids interconversion among the reduced forms and the oxidized forms.ResultsWe compared seven different solvents for quenching and extraction of cultured mammalian cells and mouse tissues: a cold aqueous buffer commonly used in enzyme assays with and without detergent, hot aqueous buffer, and cold organic mixtures (80% methanol, buffered 75% acetonitrile, and acidic 40:40:20 acetonitrile:methanol:water with either 0.02 M or 0.1 M formic acid). Extracts were analyzed by liquid chromatography-mass spectrometry (LC-MS). To monitor the metabolite interconversion, cells were grown in 13C6-glucose medium, and unlabeled standards were spiked into the extraction solvents. Interconversion between the oxidized and reduced forms was substantial except for the enzyme assay buffer with detergent, 80% methanol and 40:40:20 acetonitrile:methanol:water, with the 0.1 M formic acid mix giving the least interconversion and best recoveries. Absolute NAD+, NADH, NADP+, and NADPH concentrations in cells and mouse tissues were measured with this approach.InnovationWe found that the interconversion between the reduced and oxidized forms during extraction is a major barrier to accurately measuring NADPH/NADP+ and NADH/NAD+ ratios. Such interconversion can be monitored by isotope labeling cells and spiking NAD(P)(H) standards.ConclusionExtraction with 40:40:20 acetonitrile:methanol:water with 0.1 M formic acid decreases interconversion and, therefore, is suitable for measurement of redox cofactor ratios using LC-MS. This solvent is also useful for general metabolomics. Samples should be neutralized immediately after extraction to avoid acid-catalyzed degradation. When LC-MS is not available and enzyme assays are accordingly used, inclusion of detergent in the aqueous extraction buffer reduces interconversion. Antioxid. Redox Signal. 28, 167-179.

Dataset Information

Nicotinamide adenine dinucleotide suppresses epileptogenesis at an early stage.

Publications

Nicotinamide adenine dinucleotide suppresses epileptogenesis at an early stage.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets