scholarly journals The Biochemical Profile of Post-Mortem Brain from People Who Suffered from Epilepsy Reveals Novel Insights into the Etiopathogenesis of the Disease

Metabolites ◽  
2020 ◽  
Vol 10 (6) ◽  
pp. 261
Author(s):  
Ashna M. Lalwani ◽  
Ali Yilmaz ◽  
Halil Bisgin ◽  
Zafer Ugur ◽  
Sumeyya Akyol ◽  
...  
Keyword(s):  
1H Nmr ◽  
Predictive Biomarkers ◽  
Enrichment Analysis ◽  
Adenosine Monophosphate ◽  
Postmortem Brain ◽  
Proton Nuclear Magnetic Resonance ◽  
Post Mortem ◽  
Post Mortem Brain ◽  
Postmortem Brain Tissue ◽  
Concentration Changes

Epilepsy not-otherwise-specified (ENOS) is one of the most common causes of chronic disorders impacting human health, with complex multifactorial etiology and clinical presentation. Understanding the metabolic processes associated with the disorder may aid in the discovery of preventive and therapeutic measures. Post-mortem brain samples were harvested from the frontal cortex (BA8/46) of people diagnosed with ENOS cases (n = 15) and age- and sex-matched control subjects (n = 15). We employed a targeted metabolomics approach using a combination of proton nuclear magnetic resonance (1H-NMR) and direct injection/liquid chromatography tandem mass spectrometry (DI/LC-MS/MS). We accurately identified and quantified 72 metabolites using 1H-NMR and 159 using DI/LC-MS/MS. Among the 212 detected metabolites, 14 showed significant concentration changes between ENOS cases and controls (p < 0.05; q < 0.05). Of these, adenosine monophosphate and O-acetylcholine were the most commonly selected metabolites used to develop predictive models capable of discriminating between ENOS and unaffected controls. Metabolomic set enrichment analysis identified ethanol degradation, butyrate metabolism and the mitochondrial beta-oxidation of fatty acids as the top three significantly perturbed metabolic pathways. We report, for the first time, the metabolomic profiling of postmortem brain tissue form patients who died from epilepsy. These findings can potentially expand upon the complex etiopathogenesis and help identify key predictive biomarkers of ENOS.

scholarly journals Metabolomic Profiling of Cerebral Palsy Brain Tissue Reveals Novel Central Biomarkers and Biochemical Pathways Associated with the Disease: A Pilot Study

Metabolites ◽  
2019 ◽  
Vol 9 (2) ◽  
pp. 27 ◽  
Author(s):  
Zeynep Alpay Savasan ◽  
Ali Yilmaz ◽  
Zafer Ugur ◽  
Buket Aydas ◽  
Ray Bahado-Singh ◽  
...  
Keyword(s):  
Cerebral Palsy ◽  
Brain Tissue ◽  
1H Nmr ◽  
Enrichment Analysis ◽  
Estrogen Metabolism ◽  
Post Mortem ◽  
Tissue Samples ◽  
Motor Disability ◽  
Metabolomic Profiling ◽  
Concentration Changes

Cerebral palsy (CP) is one of the most common causes of motor disability in childhood, with complex and heterogeneous etiopathophysiology and clinical presentation. Understanding the metabolic processes associated with the disease may aid in the discovery of preventive measures and therapy. Tissue samples (caudate nucleus) were obtained from post-mortem CP cases (n = 9) and age- and gender-matched control subjects (n = 11). We employed a targeted metabolomics approach using both 1H NMR and direct injection liquid chromatography-tandem mass spectrometry (DI/LC-MS/MS). We accurately identified and quantified 55 metabolites using 1H NMR and 186 using DI/LC-MS/MS. Among the 222 detected metabolites, 27 showed significant concentration changes between CP cases and controls. Glycerophospholipids and urea were the most commonly selected metabolites used to develop predictive models capable of discriminating between CP and controls. Metabolomics enrichment analysis identified folate, propanoate, and androgen/estrogen metabolism as the top three significantly perturbed pathways. We report for the first time the metabolomic profiling of post-mortem brain tissue from patients who died from cerebral palsy. These findings could help to further investigate the complex etiopathophysiology of CP while identifying predictive, central biomarkers of CP.

scholarly journals Brain weight in suicide

2000 ◽  
Vol 177 (3) ◽  
pp. 257-261 ◽  
Author(s):  
Emad Salib ◽  
George Tadros
Keyword(s):  
Age Groups ◽  
Brain Weight ◽  
Postmortem Brain ◽  
Critical Examination ◽  
Elderly Persons ◽  
Post Mortem ◽  
Post Mortem Brain ◽  
Significant Difference ◽  
Self Harm ◽  
Set Up

BackgroundThere is little available literature on the effect of suicide methods on brain weight.AimsTo explore variations in postmortem brain weight in different methods of fatal self-harm (FSH) and in deaths from natural causes.MethodA review of a sample of coroners' records of elderly persons (60 and above). Verdicts of suicide, misadventure and open verdicts were classified as FSH. Post-mortem brain weight for 142 FSH victims and 150 victims of unexpected, sudden or unexplained death due to natural causes, and from various methods of FSH, were compared.ResultsBrain weight of victims of FSH was significantly higher than of those who died of natural causes (P<0.01); brain weights in both groups were within the normal range for this age group. There was no significant difference in brain weight between different methods of FSH (P>0.05).ConclusionsThe findings require critical examination and further research, to include data from younger age groups. A regional or national suicide neuropathological database could be set up if all victims of FSH underwent routine neurohistochemical post-mortem examination.

Post-Mortem Diagnosis of Hypoxia by Means of Brain Lactic Acid Concentration

1958 ◽  
Vol 192 (3) ◽  
pp. 577-580 ◽  
Author(s):  
Donald D. Van Fossan ◽  
Robert T. Clark
Keyword(s):  
Lactic Acid ◽  
Acid Concentration ◽  
Oxygen Deficiency ◽  
Postmortem Brain ◽  
Post Mortem ◽  
Lactic Acid Concentration ◽  
Altitude Exposure ◽  
Post Mortem Brain ◽  
Exposure Levels ◽  
The Brain

Simulated altitude exposure elevates the postmortem brain lactic acid concentration up to 98 mg/100 gm above controls depending on species used, duration, and intensity of exposure. The sharp difference in post-mortem brain lactic acid concentration between altitude exposed animals and controls remains demonstrable for the longest postmortem intervals studied (20 hr. in the dog, 30 hr. in the rabbit, and 6 hr. in the rat). Upon recovery from altitude exposure the brain lactic acid and/or precursors return toward pre-exposure levels in accordance with first order reaction kinetics during the first few minutes. The velocity constant is .32 and the half-life is 2.2 minutes. Elevated post-mortem brain lactic acid concentration is a constant finding in animals which were hypoxic at the time of death and appears to be a suitable criterion for establishing ante-mortem altitude exposure or other physiologically similar oxygen deficiency situations.

scholarly journals 1H-NMR Metabolomics Identifies Significant Changes in Metabolism over Time in a Porcine Model of Severe Burn and Smoke Inhalation

Metabolites ◽  
2019 ◽  
Vol 9 (7) ◽  
pp. 142
Author(s):  
Cole Hendrickson ◽  
Katharina Linden ◽  
Stefan Kreyer ◽  
Gregory Beilman ◽  
Vittorio Scaravilli ◽  
...  
Keyword(s):  
Nmr Spectroscopy ◽  
1H Nmr ◽  
1H Nmr Spectroscopy ◽  
Porcine Model ◽  
Burn Injury ◽  
Smoke Inhalation ◽  
Proton Nuclear Magnetic Resonance ◽  
Severe Burn ◽  
Concentration Changes ◽  
Over Time

Burn injury initiates a hypermetabolic response leading to muscle catabolism and organ dysfunction but has not been well-characterized by high-throughput metabolomics. We examined changes in metabolism over the first 72 h post-burn using proton nuclear magnetic resonance (1H-NMR) spectroscopy and serum from a porcine model of severe burn injury. We sought to quantify the changes in metabolism that occur over time in response to severe burn and smoke inhalation in this preliminary study. Fifteen pigs received 40% total body surface area (TBSA) burns with additional pine bark smoke inhalation. Arterial blood was drawn at baseline (pre-burn) and every 24 h until 72 h post-injury or death. The aqueous portion of each serum sample was analyzed using 1H-NMR spectroscopy and metabolite concentrations were used for principal component analysis (PCA). Thirty-eight metabolites were quantified in 39 samples. Of these, 31 showed significant concentration changes over time (p < 0.05). PCA revealed clustering of samples by time point on a 2D scores plot. The first 48 h post-burn were characterized by high concentrations of histamine, alanine, phenylalanine, and tyrosine. Later timepoints were characterized by rising concentrations of 2-hydroxybutyrate, 3-hydroxybutyrate, acetoacetate, and isovalerate. No significant differences in metabolism related to mortality were observed. Our work highlights the accumulation of organic acids resulting from fatty acid catabolism and oxidative stress. Further studies will be required to relate accumulation of the four organic carboxylates identified in this analysis to outcomes from burn injury.

scholarly journals Single-Cell RNA Sequencing in Parkinson’s Disease

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 368
Author(s):  
Shi-Xun Ma ◽  
Su Bin Lim
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Single Cell ◽  
Rna Sequencing ◽  
Rna Degradation ◽  
Postmortem Brain ◽  
Cell Type ◽  
New Findings ◽  
Postmortem Brain Tissue ◽  
Technical Challenges

Single-cell and single-nucleus RNA sequencing (sc/snRNA-seq) technologies have enhanced the understanding of the molecular pathogenesis of neurodegenerative disorders, including Parkinson’s disease (PD). Nonetheless, their application in PD has been limited due mainly to the technical challenges resulting from the scarcity of postmortem brain tissue and low quality associated with RNA degradation. Despite such challenges, recent advances in animals and human in vitro models that recapitulate features of PD along with sequencing assays have fueled studies aiming to obtain an unbiased and global view of cellular composition and phenotype of PD at the single-cell resolution. Here, we reviewed recent sc/snRNA-seq efforts that have successfully characterized diverse cell-type populations and identified cell type-specific disease associations in PD. We also examined how these studies have employed computational and analytical tools to analyze and interpret the rich information derived from sc/snRNA-seq. Finally, we highlighted important limitations and emerging technologies for addressing key technical challenges currently limiting the integration of new findings into clinical practice.

scholarly journals Neuroendocrine Neoplasms: Identification of Novel Metabolic Circuits of Potential Diagnostic Utility

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 374
Author(s):  
Beatriz Jiménez ◽  
Mei Ran Abellona U ◽  
Panagiotis Drymousis ◽  
Michael Kyriakides ◽  
Ashley K. Clift ◽  
...  
Keyword(s):  
1H Nmr ◽  
Cancer Metabolism ◽  
Proton Nuclear Magnetic Resonance ◽  
Neuroendocrine Neoplasms ◽  
Resonance Spectroscopy ◽  
Diagnostic Utility ◽  
Signalling Molecules ◽  
Prognostic Accuracy ◽  
Diagnostic Potential ◽  
Healthy Control

The incidence of neuroendocrine neoplasms (NEN) is increasing, but established biomarkers have poor diagnostic and prognostic accuracy. Here, we aim to define the systemic metabolic consequences of NEN and to establish the diagnostic utility of proton nuclear magnetic resonance spectroscopy (1H-NMR) for NEN in a prospective cohort of patients through a single-centre, prospective controlled observational study. Urine samples of 34 treatment-naïve NEN patients (median age: 59.3 years, range: 36–85): 18 had pancreatic (Pan) NEN, of which seven were functioning; 16 had small bowel (SB) NEN; 20 age- and sex-matched healthy control individuals were analysed using a 600 MHz Bruker 1H-NMR spectrometer. Orthogonal partial-least-squares-discriminant analysis models were able to discriminate both PanNEN and SBNEN patients from healthy control (Healthy vs. PanNEN: AUC = 0.90, Healthy vs. SBNEN: AUC = 0.90). Secondary metabolites of tryptophan, such as trigonelline and a niacin-related metabolite were also identified to be universally decreased in NEN patients, while upstream metabolites, such as kynurenine, were elevated in SBNEN. Hippurate, a gut-derived metabolite, was reduced in all patients, whereas other gut microbial co-metabolites, trimethylamine-N-oxide, 4-hydroxyphenylacetate and phenylacetylglutamine, were elevated in those with SBNEN. These findings suggest the existence of a new systems-based neuroendocrine circuit, regulated in part by cancer metabolism, neuroendocrine signalling molecules and gut microbial co-metabolism. Metabonomic profiling of NEN has diagnostic potential and could be used for discovering biomarkers for these tumours. These preliminary data require confirmation in a larger cohort.

scholarly journals Vapor Phase Modification for Selective Enrichment of Grafted Styrene/Acrylonitrile onto Carbon Nanotubes Via ATRP

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 459
Author(s):  
Maryam Azadbakht ◽  
Elnaz Esmizadeh ◽  
Ali Vahidifar ◽  
Tizazu H. Mekonnen ◽  
Mehdi Salami-Kalajahi
Keyword(s):  
Carbon Nanotubes ◽  
1H Nmr ◽  
Vapor Phase ◽  
Proton Nuclear Magnetic Resonance ◽  
Acid Vapor ◽  
Selective Enrichment ◽  
Pristine Mwcnts ◽  
Morphological Studies ◽  
Phase Oxidation ◽  
Multi Walled Carbon Nanotubes

Nitric acid vapor phase oxidation of multi-walled carbon nanotubes (MWCNTs) was proposed as a promising technique to fabricate poly styrene-co-acrylonitrile (SAN)-grafted-CNTs via atom transfer radical polymerization (ATRP). The in-situ ATRP grafting approach was successfully employed to graft polystyrene (PS), SAN and polyacrylonitrile (PAN), onto the convex surfaces of pristine MWCNTs (PCNT) and acid-functionalized MWCNTs (FCNT). Fourier transform infrared spectroscopy (FTIR), proton nuclear magnetic resonance (1H-NMR), and thermogravimetric analysis (TGA) confirmed the effectiveness of the modification via the ATRP grafting approach. The molar composition of acrylonitrile in the synthesized copolymer on the surface of CNTs for an FCNTs was calculated to be about 80% and 67.5% by 1H-NMR and TGA respectively, whereas the value is lower for PCNTs. Morphological studies showed that SAN-grafted FCNTs exhibit rougher surface morphology compared to the SAN-grafted PCNTs. Moreover, the higher diameter of the FCNTs indicated the higher polymer content, which was coated onto CNTs functionalized by vapor-phase oxidation. Therefore, the vapor phase oxidation strategy employed in this study could be utilized as a general method to prepare CNTs which can serve as an ATRP macroinitiator for the fabrication of various polymer grafted CNTs.

scholarly journals Protein farnesylation is upregulated in Alzheimer’s human brains and neuron-specific suppression of farnesyltransferase mitigates pathogenic processes in Alzheimer’s model mice

2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Angela Jeong ◽  
Shaowu Cheng ◽  
Rui Zhong ◽  
David A. Bennett ◽  
Martin O. Bergö ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Small Gtpases ◽  
Specific Role ◽  
Postmortem Brain ◽  
Effective Prevention ◽  
Postmortem Brain Tissue ◽  
Mtorc1 Signaling ◽  
Behavioral Assessments ◽  
Human Brains

AbstractThe pathogenic mechanisms underlying the development of Alzheimer’s disease (AD) remain elusive and to date there are no effective prevention or treatment for AD. Farnesyltransferase (FT) catalyzes a key posttranslational modification process called farnesylation, in which the isoprenoid farnesyl pyrophosphate is attached to target proteins, facilitating their membrane localization and their interactions with downstream effectors. Farnesylated proteins, including the Ras superfamily of small GTPases, are involved in regulating diverse physiological and pathological processes. Emerging evidence suggests that isoprenoids and farnesylated proteins may play an important role in the pathogenesis of AD. However, the dynamics of FT and protein farnesylation in human brains and the specific role of neuronal FT in the pathogenic progression of AD are not known. Here, using postmortem brain tissue from individuals with no cognitive impairment (NCI), mild cognitive impairment (MCI), or Alzheimer’s dementia, we found that the levels of FT and membrane-associated H-Ras, an exclusively farnesylated protein, and its downstream effector ERK were markedly increased in AD and MCI compared with NCI. To elucidate the specific role of neuronal FT in AD pathogenesis, we generated the transgenic AD model APP/PS1 mice with forebrain neuron-specific FT knockout, followed by a battery of behavioral assessments, biochemical assays, and unbiased transcriptomic analysis. Our results showed that the neuronal FT deletion mitigates memory impairment and amyloid neuropathology in APP/PS1 mice through suppressing amyloid generation and reversing the pathogenic hyperactivation of mTORC1 signaling. These findings suggest that aberrant upregulation of protein farnesylation is an early driving force in the pathogenic cascade of AD and that targeting FT or its downstream signaling pathways presents a viable therapeutic strategy against AD.

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