Correction: Metabolic Profiling of Dividing Cells in Live Rodent Brain by Proton Magnetic Resonance Spectroscopy (1HMRS) and LCModel Analysis
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SUBMITTER: The Staff
PROVIDER: S-EPMC4136929 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Altered brain metabolism is likely to be an important contributor to normal cognitive decline and brain pathology in elderly individuals. To characterize the metabolic changes associated with normal brain aging, we used high-field proton magnetic resonance spectroscopy in vivo to quantify 20 neurochemicals in the hippocampus and sensorimotor cortex of young adult and aged rats. We found significant differences in the neurochemical profile of the aged brain when compared with younger adults, including lower aspartate, ascorbate, glutamate, and macromolecules, and higher glucose, myo-inositol, N-acetylaspartylglutamate, total choline, and glutamine. These neurochemical biomarkers point to specific cellular mechanisms that are altered in brain aging, such as bioenergetics, oxidative stress, inflammation, cell membrane turnover, and endogenous neuroprotection. Proton magnetic resonance spectroscopy may be a valuable translational approach for studying mechanisms of brain aging and pathology, and for investigating treatments to preserve or enhance cognitive function in aging.
| S-EPMC4174428 | biostudies-literature
Project description:AimsMaternal metabolic disorders place the mother at risk for negative pregnancy outcomes with potentially long-term health impacts for the child. Metabolic syndrome, a cluster of features associated with increased risk of metabolic disorders, such as cardiovascular disease, diabetes and stroke, affects roughly one in five Canadians. Metabolomics is a relatively new technique that may be a useful tool to identify women at risk of metabolic disorders. This study set out to characterize urinary metabolic biomarkers of pregnant women with obesity and of pregnant women who later developed gestational diabetes mellitus (pre-GDM), compared to controls.Methods and materialsSecond trimester urine samples were collected through the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort and examined with 1H nuclear magnetic resonance (NMR) spectroscopy. Multivariate analysis was used to examine group differences, and machine learning feature selection tools identified the metabolites contributing to separation.ResultsObesity and pre-GDM metabolomes were distinct from controls and from each other. In each comparison, the glycine, serine and threonine pathways were the most impacted. Pantothenate, formic acid and glycine were downregulated by obesity, while formic acid, dimethylamine and galactose were downregulated in pre-GDM. The three most impacted metabolites for the comparison of obesity versus pre-GDM groups were upregulated creatine/caffeine, downregulated sarcosine/dimethylamine and upregulated maltose/sucrose in individuals who later developed GDM.ConclusionThese findings suggest a role for urinary metabolomics in the prediction of GDM and metabolic marker identification for potential diagnostics and prognostics in women at risk.
| S-EPMC7831222 | biostudies-literature
Project description:Ketosis metabolic research on lactating dairy cattle has been conducted worldwide; however, there have been very few Korean studies. Biofluids from lactating dairy cattle are necessary to study ketosis metabolic diseases. Six Holstein cows were divided into two groups (healthy (CON) and subclinical ketosis diagnosed (SCK)). Rumen fluid and milk samples were collected using a stomach tube and a pipeline milking system, respectively. Metabolites were determined using proton nuclear magnetic resonance (NMR) spectroscopy and they were identified and quantified using the Chenomx NMR Suite 8.4 software and Metaboanalyst 5.0. In the rumen fluid of the SCK group, butyrate, sucrose, 3-hydroxybutyrate, maltose, and valerate levels were significantly higher than in the CON group, which showed higher levels of N,N-dimethylformamide, acetate, glucose, and propionate were significantly higher. Milk from the SCK group showed higher levels of maleate, 3-hydroxybutyrate, acetoacetate, galactonate, and 3-hydroxykynurenine than that from the CON group, which showed higher levels of galactitol, 1,3-dihydroxyacetone, γ-glutamylphenylalanine, 5-aminolevulinate, acetate, and methylamine. Some metabolites are associated with ketosis diseases and the quality of rumen fluid and milk. This report will serve as a future reference guide for ketosis metabolomics studies in Korea.
| S-EPMC8471376 | biostudies-literature
Project description:INTRODUCTION:Facioscapulohumeral muscular dystrophy (FSHD) is a hereditary disorder that causes progressive muscle wasting. This study evaluates the use of proton magnetic resonance spectroscopy (1 H MRS) as a biomarker of muscle strength and function in FSHD. METHODS:Thirty-six individuals with FSHD and 15 healthy controls underwent multivoxel 1 H MRS of a cross-section of the mid-thigh. Concentrations of creatine, intramyocellular and extramyocellular lipids, and trimethylamine (TMA)-containing compounds in skeletal muscle were calculated. Metabolite concentrations for individuals with FSHD were compared with those of controls. The relationship between metabolite concentrations and muscle strength was also examined. RESULTS:The TMA/creatine (Cr) ratio in individuals with FSHD was reduced compared with controls. The TMA/Cr ratio in the hamstrings also showed a moderate linear correlation with muscle strength. DISCUSSION:1 H MRS offers a potential method of detecting early muscle pathology in FSHD prior to the development of fat infiltration. Muscle Nerve 57: 958-963, 2018.
| S-EPMC5951728 | biostudies-literature
Project description:This chapter critically reviews brain proton magnetic resonance spectroscopy ((1)H MRS) studies performed since 1994 in individuals with alcohol use disorders (AUD). We describe the neurochemicals that can be measured in vivo at the most common magnetic field strengths, summarize our knowledge about their general brain functions, and briefly explain some basic human (1)H MRS methods. Both cross-sectional and longitudinal research of individuals in treatment and of treatment-naïve individuals with AUD are discussed and interpreted on the basis of reported neuropathology. As AUDs are highly comorbid with chronic cigarette smoking and illicit substance abuse, we also summarize reports on their respective influences on regional proton metabolite levels. After reviewing research on neurobiologic correlates of relapse and genetic influences on brain metabolite levels, we finish with suggestions on future directions for (1)H MRS studies in AUDs. The review demonstrates that brain metabolic alterations associated with AUDs as well as their cognitive correlates are not simply a consequence of chronic alcohol consumption. Future MR research of AUDs in general has to be better prepared - and supported - to study clinically complex relationships between personality characteristics, comorbidities, neurogenetics, lifestyle, and living environment, as all these factors critically affect an individual's neurometabolic profile. (1)H MRS is uniquely positioned to tackle these complexities by contributing to a comprehensive biopsychosocial profile of individuals with AUD: it can provide non-invasive biochemical information on select regions of the brain at comparatively low overall cost for the ultimate purpose of informing more efficient treatments of AUDs.
| S-EPMC4876042 | biostudies-literature
Project description:Can 1H Magnetic Resonance Spectroscopy (MRS) be used to obtain information about the molecules and metabolites in live human spermatozoa?Percoll-based density gradient centrifugation (DGC) followed by a further two washing steps, yielded enough sperm with minimal contamination (<0.01%) from seminal fluid to permit effective MRS which detected significant differences (P < 0.05) in the choline/glycerophosphocholine (GPC), lipid and lactate regions of the 1H MRS spectrum between sperm in the pellet and those from the 40%/80% interface.Current methods to examine sperm are either limited in their value (e.g. semen analysis) or are destructive (e.g. immunohistochemistry, sperm DNA testing). A few studies have previously used MRS to examine sperm, but these have either looked at seminal plasma from men with different ejaculate qualities or at the molecules present in pooled samples of lyophilized sperm.Sperm suspended in phosphate buffered saline (PBS) at 37°C were examined by 1H MRS scanning using a 1H excitation-sculpting solvent suppression sequence after recovery from fresh ejaculates by one of three different methods: (i) simple centrifugation; (ii) DGC with one wash; or (iii) DGC with two washes. In the case of DGC, sperm were collected both from the pellet ('80%' sperm) and the 40/80 interface ('40%' sperm). Spectrum processing was carried out using custom Matlab scripts to determine; the degree of seminal plasma/Percoll contamination, the minimum sperm concentration for 1H MRS detection and differences between the 1H MRS spectra of '40%' and '80%' sperm.DGC with two washes minimized the 1H MRS peak intensity for both seminal plasma and Percoll/PBS solution contamination while retaining sperm specific peaks. For the MRS scanner used in this study, the minimum sperm concentration required to produce a choline/GPC 1H MRS peak greater than 3:1 signal to noise ratio (SNR) was estimated at ~3 × 106/ml. The choline/GPC and lactate/lipid regions of the 1H spectrum were significantly different by two-way ANOVA analysis (P < 0.0001; n = 20). ROC curve analysis of these region showed significant ability to distinguish between the two sperm populations: choline/GPC ROC AUC = 0.65-0.67, lactate/lipid ROC AUC = 0.86-0.87.Only 3-4 semen samples were used to assess the efficacy of each sperm washing protocol that were examined. The estimated minimum sperm concentration required for MRS is specific to the hardware used in our study and may be different in other spectrometers. Spectrum binning is a low resolution analysis method that sums MRS peaks within a chemical shift range. This can obscure the identity of which metabolite(s) are responsible for differences between sperm populations. Further work is required to determine the relative contribution of somatic cells to the MRS spectrum from the '40%' and '80%' sperm.1H MRS can provide information about the molecules present in live human sperm and may therefore permit the study of the underlying functional biology or metabolomics of live sperm. Given the relatively low concentration of sperm required to obtain a suitable MRS signal (~3 × 106/ml), this could be carried out on sperm from men with oligo-, astheno- or teratozoospermia. This may lead to the development of new diagnostic tests or ultimately novel treatments for male factor infertility.This work was supported by the Medical Research Council Grant MR/M010473/1. The authors declare no conflicts of interest.
| S-EPMC5909857 | biostudies-other
Project description:There is an urgent need for a better understanding of the pathophysiology of cognitive impairment in syndromes associated with frontotemporal lobar degeneration. Here, we used magnetic resonance spectroscopy to quantify metabolite deficits in sixty patients with a clinical syndrome associated with frontotemporal lobar degeneration (behavioural variant frontotemporal dementia n=11, progressive supranuclear palsy n=26, corticobasal syndrome n=11, primary progressive aphasias n=12), and 38 age- and sex-matched healthy controls. We measured nine metabolites in the right inferior frontal gyrus, superior temporal gyrus and right primary visual cortex. Metabolite concentrations were corrected for age, sex, and partial volume then compared with cognitive and behavioural measures using canonical correlation analysis. Metabolite concentrations varied significantly by brain region and diagnosis (region x metabolite x diagnosis interaction F(64)=1.73, p<0.001, corrected for age, sex, and atrophy within the voxel). N-acetyl aspartate and glutamate concentrations were reduced in the right prefrontal cortex in behavioural variant frontotemporal dementia and progressive supranuclear palsy, even after partial volume correction. The reduction of these metabolites was associated with executive dysfunction and behavioural impairment (canonical correlation analysis R=0.85, p<0.001).
| S-EPMC8776136 | biostudies-literature
Project description:BackgroundPantothenate kinase (PANK) is the first and rate-controlling enzymatic step in the only pathway for cellular coenzyme A (CoA) biosynthesis. PANK-associated neurodegeneration (PKAN), formerly known as Hallervorden-Spatz disease, is a rare, life-threatening neurologic disorder that affects the CNS and arises from mutations in the human PANK2 gene. Pantazines, a class of small molecules containing the pantazine moiety, yield promising therapeutic effects in an animal model of brain CoA deficiency. A reliable technique to identify the neurometabolic effects of PANK dysfunction and to monitor therapeutic responses is needed.MethodsWe applied 1H magnetic resonance spectroscopy as a noninvasive technique to evaluate the therapeutic effects of the newly developed Pantazine BBP-671.Results1H MRS reliably quantified changes in cerebral metabolites, including glutamate/glutamine, lactate, and N-acetyl aspartate in a neuronal Pank1 and Pank2 double-knockout (SynCre+ Pank1,2 dKO) mouse model of brain CoA deficiency. The neuronal SynCre+ Pank1,2 dKO mice had distinct decreases in Glx/tCr, NAA/tCr, and lactate/tCr ratios compared to the wildtype matched control mice that increased in response to BBP-671 treatment.ConclusionsBBP-671 treatment completely restored glutamate/glutamine levels in the brains of the mouse model, suggesting that these metabolites are promising clinically translatable biomarkers for future therapeutic trials.
| S-EPMC8867880 | biostudies-literature
Project description:Despite maximally-safe resection of the MRI-defined contrast-enhanced (CE) central tumor area and chemo-radiotherapy, most glioblastoma patients relapse within one year in peritumor FLAIR regions. Spectroscopic MRI (MRSI) can discriminate metabolic tumor areas with higher recurrence potential as CNI+ regions (Choline/N-acetyl-aspartate Index>2) can predict relapse sites. As relapses are mainly imputed to glioblastoma stem-like cells (GSC), CNI+ areas might be GSC-enriched. We conducted a prospective trial in 16 GBM patients subjected to preoperative MRSI/MRI and surgery/chemo-radiotherapy to investigate GSC content in CNI+ versus CNI- biopsies from CE/FLAIR. Biopsy characterization by RNAseq revealed that FLAIR/CNI+ areas were enriched in stem-related gene signature, but also in pathways related to DNA repair, adhesion/migration and mitochondrial bioenergetics.
2023-11-03 | GSE239379 | GEO
Project description:In the past decades, new methods for tumor staging, restaging, treatment response monitoring, and recurrence detection of a variety of cancers have emerged in conjunction with the state-of-the-art positron emission tomography with 18F-fluorodeoxyglucose ([18F]-FDG PET). 13C magnetic resonance spectroscopic imaging (13CMRSI) is a minimally invasive imaging method that enables the monitoring of metabolism in vivo and in real time. As with any other method based on 13C nuclear magnetic resonance (NMR), it faces the challenge of low thermal polarization and a subsequent low signal-to-noise ratio due to the relatively low gyromagnetic ratio of 13C and its low natural abundance in biological samples. By overcoming these limitations, dynamic nuclear polarization (DNP) with subsequent sample dissolution has recently enabled commonly used NMR and magnetic resonance imaging (MRI) systems to measure, study, and image key metabolic pathways in various biological systems. A particularly interesting and promising molecule used in 13CMRSI is [1-13C]pyruvate, which, in the last ten years, has been widely used for in vitro, preclinical, and, more recently, clinical studies to investigate the cellular energy metabolism in cancer and other diseases. In this article, we outline the technique of dissolution DNP using a 3.35 T preclinical DNP hyperpolarizer and demonstrate its usage in in vitro studies. A similar protocol for hyperpolarization may be applied for the most part in in vivo studies as well. To do so, we used lactate dehydrogenase (LDH) and catalyzed the metabolic reaction of [1-13C]pyruvate to [1-13C]lactate in a prostate carcinoma cell line, PC3, in vitro using 13CMRSI.
| S-EPMC5226623 | biostudies-literature