Dataset Information

Single-Voxel ¹ H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD⁺ ) in humans at 7T using a 32-channel volume coil.

ABSTRACT:

Purpose

Reliable monitoring of tissue nicotinamide adenine dinucleotide (NAD⁺ ) concentration may provide insights on its roles in normal and pathological aging. In the present study, we report a ¹ H MRS pulse sequence for the in vivo, localized ¹ H MRS detection of NAD⁺ from the human brain.

Methods

Studies were carried out on a 7T Siemens MRI scanner using a 32-channel product volume coil. The pulse sequence consisted of a spectrally selective low bandwidth E-BURP-1 90° pulse. PRESS localization was achieved using optimized Shinnar-Le Roux 180° pulses and overlapping gradients were used to minimize the TE. The reproducibility of NAD⁺ quantification was measured in 11 healthy volunteers. The association of cerebral NAD⁺ with age was assessed in 16 healthy subjects 26-78 years old.

Results

Spectra acquired from a voxel placed in subjects' occipital lobe consisted of downfield peaks from the H₂ , H₄ , and H₆ protons of the nicotinamide moiety of NAD⁺ between 8.9-9.35 ppm. The mean ± SD within-session and between-session coefficients of variation were found to be 6.14 ± 2.03% and 6.09 ± 3.20%, respectively. In healthy volunteers, an age-dependent decline of the NAD⁺ levels in the brain was also observed (? = -1.24 ?M/y, SE = 0.21, P < 0.001).

Conclusion

We demonstrated the feasibility and robustness of a newly developed ¹ H MRS technique to measure localized cerebral NAD⁺ at 7T MRI using a commercially available RF head coil. This technique may be further applied to detect and quantify NAD⁺ from different regions of the brain as well as from other tissues.

SUBMITTER: Bagga P

PROVIDER: S-EPMC6879788 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Single-Voxel <sup>1</sup> H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD<sup>+</sup> ) in humans at 7T using a 32-channel volume coil.

Bagga Puneet P Hariharan Hari H Wilson Neil E NE Beer Joanne C JC Shinohara Russell T RT Elliott Mark A MA Baur Joseph A JA Marincola Francesco M FM Witschey Walter R WR Haris Mohammad M Detre John A JA Reddy Ravinder R

Magnetic resonance in medicine 20190910 3

<h4>Purpose</h4>Reliable monitoring of tissue nicotinamide adenine dinucleotide (NAD<sup>+</sup> ) concentration may provide insights on its roles in normal and pathological aging. In the present study, we report a <sup>1</sup> H MRS pulse sequence for the in vivo, localized <sup>1</sup> H MRS detection of NAD<sup>+</sup> from the human brain.<h4>Methods</h4>Studies were carried out on a 7T Siemens MRI scanner using a 32-channel product volume coil. The pulse sequence consisted of a spectrally s ...[more]

PMID: 31502710

Similar Datasets

Project description:One of the biochemical abnormalities found in diabetic tissues is a decrease in the cytosolic oxidized to reduced forms of the nicotinamide adenine dinucleotide ratio (NAD+ /NADH also known as pseudohypoxia) caused by oxidation of excessive substrates (glucose through the polyol pathway, free fatty acids and lactate). Subsequently, a decline in NAD+ levels as a result of the activation of poly adenine nucleotide diphosphate-ribose polymerase (mainly in type 1 diabetes) or the inhibition of adenine nucleotide monophosphate-activated protein kinase (in type 2 diabetes). Thus, replenishment of NAD+ levels by nicotinamide-related compounds could be beneficial. However, these compounds also increase nicotinamide catabolites that cause oxidative stress. This is particularly troublesome for patients with diabetes, because they have impaired nicotinamide salvage pathway reactions at the level of nicotinamide phosphoribosyl transferase and phosphoribosyl pyrophosphate, which occurs by the following mechanisms. First, phosphoribosyl pyrophosphate synthesis from pentose phosphate pathway is compromised by a decrease in plasma thiamine and transketolase activity. Second, nicotinamide phosphoribosyl transferase expression is decreased because of reduced adenosine monophosphate-activated protein kinase activity, which occurs in type 2 diabetes. The adenosine monophosphate-activated protein kinase inhibition is caused by an activation of protein kinase C and D1 as a result of enhanced diacylglycerol synthesis caused by pseudohypoxia and increased fatty acids levels. In this regard, nicotinamide-related compounds should be given with caution to treat diabetes. To minimize the risk and maximize the benefit, nicotinamide-related compounds should be taken with insulin sensitizers (for type 2 diabetes), polyphenols, benfotiamine, acetyl-L-carnitine and aldose reductase inhibitors. The efficacy of these regimens can be monitored by measuring serum NAD+ and urinary nicotinamide catabolites.

Project description:BackgroundBecause stomach adenocarcinoma (STAD) has a poor prognosis, it is necessary to explore new prognostic genes to stratify patients to guide existing individualized treatments.MethodsSurvival and clinical information, RNA-seq data and mutation data of STAD were acquired from The Cancer Genome Atlas (TCGA) database. Fifty-one nicotinamide adenine dinucleotide (NAD+) metabolism-related genes (NMRGs) were obtained from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Reactome databases. Differentially expressed NMRGs (DE-NMRGs) between STAD and normal samples were screened, and consistent clustering analysis of STAD patients was performed based on the DE-NMRGs. Survival analysis, Gene Set Enrichment Analysis (GSEA), mutation frequency analysis, immune microenvironment analysis and drug prediction were performed among different clusters. Additionally, the differentially expressed genes (DEGs) among different clusters were selected, and the intersections of DEGs and DE-NMRGs were selected as the prognostic genes. Finally, quantitative real-time polymerase chain reaction (qRT-PCR) was performed on a human gastric mucosa epithelial cell line and cancer cell line to verify the expression of the prognostic genes.ResultsA total of 27 DE-NMRGs and two clusters were selected. There was a difference in survival between clusters 1 and 2. Furthermore, 18 DE-NMRGs were significantly different between clusters 1 and 2. The different Gene Ontology (GO) biological processes and KEGG pathways between clusters 1 and 2 were mainly enriched in cyclic nucleotide mediated signaling, synaptic signaling and hedgehog signaling pathway, etc. The somatic mutation frequencies were different between the two clusters, and TTN was the highest mutated gene in the patients of the clusters 1 and 2. Additionally, eight immune cells, immune score, stromal score, and estimate score were different between clusters 1 and 2. The patients in cluster 2 were sensitive to CTLA4 inhibitor treatment. Furthermore, the top five drugs (AP.24534, BX.795, Midostaurin, WO2009093927 and CCT007093) were significantly higher in cluster 1 than in cluster 2. Finally, three genes (AOX1, NNMT and PTGIS) were acquired as prognostic, and their expressions were consistent with the results of bioinformatics analysis.ConclusionsThree prognostic genes related to NAD+ metabolism in STAD were screened out, which provides a theoretical basis and reference value for future treatment and prognosis of STAD.

Dataset Information

Single-Voxel ¹ H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD⁺ ) in humans at 7T using a 32-channel volume coil.

Purpose

Methods

Results

Conclusion

Publications

Single-Voxel <sup>1</sup> H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD<sup>+</sup> ) in humans at 7T using a 32-channel volume coil.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

Single-Voxel 1 H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD+ ) in humans at 7T using a 32-channel volume coil.

Purpose

Methods

Results

Conclusion

Publications

Single-Voxel <sup>1</sup> H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD<sup>+</sup> ) in humans at 7T using a 32-channel volume coil.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Single-Voxel ¹ H MR spectroscopy of cerebral nicotinamide adenine dinucleotide (NAD⁺ ) in humans at 7T using a 32-channel volume coil.