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Xin Yu, Pei-Pei Guan, Di Zhu, Yun-Yue Liang, Tao Wang, Zhan-You Wang, Pu Wang
Alzheimer's disease (AD) is a neurodegenerative disease characterized by cognitive impairment. The neuropathological features of AD are the aggregation of extracellular amyloid β-protein (Aβ) and tau phosphorylation. Recently, AD was found to be associated with magnesium ion (Mg2+ ) deficit and tumor necrosis factor-alpha (TNF-α) elevation in the serum or brains of AD patients. To study the relationship between Mg2+ and TNF-α, we used human- or mouse-derived glial and neuronal cell lines or APP/PS1 transgenic (Tg) mice as in vitro and in vivo experimental models, respectively...
2018: Frontiers in Molecular Neuroscience
Rebecca A Dewhirst, Stephen C Fry
In the plant apoplast, ascorbate is oxidised, via dehydroascorbic acid, to O-oxalyl esters [oxalyl-l-threonate (OxT) and cyclic oxalyl-l-threonate (cOxT)]. We tested whether OxT and cOxT can donate the oxalyl group in transacylation reactions to form oxalyl-polysaccharides, potentially modifying the cell wall. [oxalyl-14 C]OxT was incubated with living spinach (Spinacia oleracea) and Arabidopsis cell-suspension cultures in the presence and absence of proposed acceptor substrates (carbohydrates). In addition, [14 C]OxT and [14 C]cOxT were incubated in vitro with cell-wall enzyme preparations plus proposed acceptor substrates...
June 8, 2018: Plant Journal: for Cell and Molecular Biology
Ying Huang, Xian Huang, Ling Zhang, Fang Han, Ke-Liang Pang, Xue Li, Jian-Ying Shen
BACKGROUND: Environmental enrichment (EE) has been shown to enhance cognitive function in mouse models of Alzheimer's disease (AD). Magnesium-L-threonate (MgT) is a compound with a newly discovered effect to rescue learning and memory function in aging and AD mice. AIM: To study the additive therapeutic effect of EE combined with MgT (EM) and the potential mechanism underlying the effects. MATERIALS AND METHODS: APP/PS1 mice were treated with EE, MgT, or combination of EE and MgT (EM) and compared for restored memory function...
January 2018: CNS Neuroscience & Therapeutics
Simone Poddighe, Federica Murgia, Lorena Lorefice, Sonia Liggi, Eleonora Cocco, Maria Giovanna Marrosu, Luigi Atzori
Multiple sclerosis (MS) is a chronic, demyelinating disease that affects the central nervous system and is characterized by a complex pathogenesis and difficult management. The identification of new biomarkers would be clinically useful for more accurate diagnoses and disease monitoring. Metabolomics, the identification of small endogenous molecules, offers an instantaneous molecular snapshot of the MS phenotype. Here the metabolomic profiles (utilizing plasma from patients with MS) were characterized with a Gas cromatography-mass spectrometry-based platform followed by a multivariate statistical analysis and comparison with a healthy control (HC) population...
December 2017: International Journal of Biochemistry & Cell Biology
Barbara Karpinska, Kaiming Zhang, Brwa Rasool, Daria Pastok, Jenny Morris, Susan R Verrall, Pete E Hedley, Robert D Hancock, Christine H Foyer
The redox state of the apoplast is largely determined by ascorbate oxidase (AO) activity. The influence of AO activity on leaf acclimation to changing irradiance was explored in wild-type (WT) and transgenic tobacco (Nicotiana tobaccum) lines containing either high [pumpkin AO (PAO)] or low [tobacco AO (TAO)] AO activity at low [low light (LL); 250 μmol m-2  s-1 ] and high [high light (HL); 1600 μmol m-2  s-1 ] irradiance and following the transition from HL to LL. AO activities changed over the photoperiod, particularly in the PAO plants...
May 2018: Plant, Cell & Environment
Ting Xu, Dai Li, Xin Zhou, Han-Dong Ouyang, Li-Jun Zhou, Hang Zhou, Hong-Mei Zhang, Xu-Hong Wei, Guosong Liu, Xian-Guo Liu
BACKGROUND: Antineoplastic agents, including vincristine, often induce neuropathic pain and magnesium deficiency clinically, but the causal link between them has not been determined. No drug is available for treating this form of neuropathic pain. METHODS: Injection of vincristine (0.1 mg · kg · day, intraperitoneally, for 10 days) was used to induce nociceptive sensitization, which was accessed with von Frey hairs and the plantar tester in adult male Sprague-Dawley rats...
June 2017: Anesthesiology
Thomas Tagoe, Daniel Deeping, Martine Hamann
Animal models have demonstrated that tinnitus is a pathology of dysfunctional excitability in the central auditory system, in particular in the dorsal cochlear nucleus (DCN) of the brainstem. We used a murine model and studied whether acoustic over-exposure leading to hearing loss and tinnitus, affects long-term potentiation (LTP) at DCN multisensory synapses. Whole cell and field potential recordings were used to study the effects on release probability and synaptic plasticity, respectively in brainstem slices...
June 2017: Experimental Neurology
Vincent Truffault, Stephen C Fry, Rebecca G Stevens, Hélène Gautier
Ascorbate content in plants is controlled by its synthesis from carbohydrates, recycling of the oxidized forms and degradation. Of these pathways, ascorbate degradation is the least studied and represents a lack of knowledge that could impair improvement of ascorbate content in fruits and vegetables as degradation is non-reversible and leads to a depletion of the ascorbate pool. The present study revealed the nature of degradation products using [14 C]ascorbate labelling in tomato, a model plant for fleshy fruits; oxalate and threonate are accumulated in leaves, as is oxalyl threonate...
March 2017: Plant Journal: for Cell and Molecular Biology
Francisco Purroy, Serafi Cambray, Gerard Mauri-Capdevila, Mariona Jové, Jordi Sanahuja, Joan Farré, Ikram Benabdelhak, Jessica Molina-Seguin, Laura Colàs-Campàs, Robert Begue, M Isabel Gil, Reinald Pamplona, Manuel Portero-Otín
BACKGROUND: Neuroimaging is essential for the diagnosis and prognosis of transient ischemic attack (TIA). The discovery of a plasmatic biomarker related to neuroimaging findings is of enormous interest because, despite its relevance, magnetic resonance diffusion weighted imaging (DWI) is not always available in all hospitals that attend to TIA patients. METHODS: Metabolomic analyses were performed by liquid chromatography coupled to mass spectrometry in order to establish the metabolomic patterns of positive DWI, DWI patterns and acute ischemic lesion volumes...
December 2016: EBioMedicine
Robert Vink
A potential neuroprotective role for magnesium in neurological disease has been appreciated for almost three decades, yet translation to the clinical arena has proven elusive. Accumulating experimental evidence continues to suggest that magnesium plays a critical role in a number of neurological conditions including headache, stress, alcohol/drug intoxication, acute brain injury, seizures, Parkinson's disease and Alzheimer's disease. Simple administration of a magnesium salt in these conditions has not always been therapeutically successful, with a number of studies showing poor penetration of serum magnesium across the blood brain barrier...
March 1, 2016: Magnesium Research: Official Organ of the International Society for the Development of Research on Magnesium
Xinshuai Zhang, Michael S Carter, Matthew W Vetting, Brian San Francisco, Suwen Zhao, Nawar F Al-Obaidi, Jose O Solbiati, Jennifer J Thiaville, Valérie de Crécy-Lagard, Matthew P Jacobson, Steven C Almo, John A Gerlt
Using a large-scale "genomic enzymology" approach, we (i) assigned novel ATP-dependent four-carbon acid sugar kinase functions to members of the DUF1537 protein family (domain of unknown function; Pfam families PF07005 and PF17042) and (ii) discovered novel catabolic pathways for d-threonate, l-threonate, and d-erythronate. The experimentally determined ligand specificities of several solute binding proteins (SBPs) for TRAP (tripartite ATP-independent permease) transporters for four-carbon acids, including d-erythronate and l-erythronate, were used to constrain the substrates for the catabolic pathways that degrade the SBP ligands to intermediates in central carbon metabolism...
July 19, 2016: Proceedings of the National Academy of Sciences of the United States of America
Qifeng Sun, Jason G Weinger, Fei Mao, Guosong Liu
Oral administration of the combination of L-threonate (threonate) and magnesium (Mg(2+)) in the form of L-Threonic acid Magnesium salt (L-TAMS) can enhance learning and memory in young rats and prevent memory decline in aging rats and in Alzheimer's disease model mice. Recent results from a human clinical trial demonstrate the efficacy of L-TAMS in restoring global cognitive abilities of older adults. Previously, we reported that neuronal intracellular Mg(2+) serves as a critical signaling molecule for controlling synapse density, a key factor that determines cognitive ability...
September 2016: Neuropharmacology
Shanshan Jia, Yunpeng Liu, Yang Shi, Yihe Ma, Yixin Hu, Meiyan Wang, Xue Li
In the adult brain, neural stem cells (NSCs) can self-renew and generate all neural lineage types, and they persist in the sub-granular zone (SGZ) of the hippocampus and the sub-ventricular zone (SVZ) of the cortex. Here, we show that dietary-supplemented - magnesium-L-threonate (MgT), a novel magnesium compound designed to elevate brain magnesium regulates the NSC pool in the adult hippocampus. We found that administration of both short- and long-term regimens of MgT, increased the number of hippocampal NSCs...
September 2016: Journal of Cellular Physiology
Yaolong Shi, Dehua Wang
Mongolian gerbils (Meriones unguiculatus) have evolved a wide thermoneutral zone (26.5-38.9 °C) and high upper critical temperature, and appear to have a high tolerance for heat exposure. Here, we use a metabolomic approach to measure global metabolite profiles for gerbils between lower (27 °C) and upper critical temperatures (38 °C) to investigate the role of metabolomic characterization in maintaining basal metabolic rates within a wide thermoneutral zone. We found that in serum and liver, 14 and 19 metabolites were significantly altered, respectively...
July 2016: Integrative Zoology
Pu Wang, Xin Yu, Pei-Pei Guan, Jing-Wen Guo, Yue Wang, Yan Zhang, Hang Zhao, Zhan-You Wang
Alzheimer's disease (AD) has been associated with magnesium ion (Mg2+ ) deficits and interleukin-1β (IL-1β) elevations in the serum or brains of AD patients. However, the mechanisms regulating IL-1β expression during Mg2+ dyshomeostasis in AD remain unknown. We herein studied the mechanism of IL-1β reduction using a recently developed compound, magnesium-L-threonate (MgT). Using human glioblastoma A172 and mouse brain D1A glial cells as an in vitro model system, we delineated the signaling pathways by which MgT suppressed the expression of IL-1β in glial cells...
May 2017: Cellular & Molecular Immunology
Amaliya Amaliya, Marja L Laine, Bruno G Loos, Ubele Van der Velden
OBJECTIVE: To assess in a periodontally diseased rural population deprived from regular dental care and having poor dietary conditions, the effect of vitamin C/calcium threonate/citrus flavonoids (VitC/Ca/Fl) supplementation on subgingival microbiota and plasma levels of vitamin C, HbA1c and hsCRP. MATERIAL & METHODS: The study population consisted of 98 subjects who previously participated in a prospective study on the natural history of periodontitis. Participants were instructed to consume one tablet/day containing 200 mg Ester C(®) calcium ascorbate, 25 mg calcium threonate and 100 mg citrus flavonoids for 90 days...
December 2015: Journal of Clinical Periodontology
Peter Spegel, Aakash Chawade, Søren Nielsen, Per Kjellbom, Michael Rützler
Deletion of the glycerol channel aquaporin-9 (Aqp9) reduces postprandial blood glucose levels in leptin receptor-deficient (db/db) obese mice on a C57BL/6 × C57BLKS mixed genetic background. Furthermore, shRNA-mediated reduction of Aqp9 expression reduces liver triacylglycerol (TAG) accumulation in a diet-induced rat model of obesity. The aim of this study was to investigate metabolic effects of Aqp9 deletion in coisogenic db/db mice of the C57BL/6 background. Aqp9(wt) db/db and Aqp9(-/-) db/db mice did not differ in body weight and liver TAG contents...
September 2015: Physiological Reports
Antonio Giovino, Federico Martinelli, Sergio Saia
The red palm weevil (RPW; Rhynchophorus ferrugineus) is spreading worldwide and severely harming many palm species. However, most studies on RPW focused on insect biology, and little information is available about the plant response to the attack. In the present experiment, we used metabolomics to study the alteration of the leaf metabolome of Phoenix canariensis at initial (1st stage) or advanced (2nd stage) attack by RPW compared with healthy (unattacked) plants. The leaf metabolome significantly varied among treatments...
April 2016: Journal of Integrative Plant Biology
Xin Yu, Pei-Pei Guan, Jing-Wen Guo, Yue Wang, Long-Long Cao, Guo-Biao Xu, Konstantinos Konstantopoulos, Zhan-You Wang, Pu Wang
Alzheimer's disease (AD) is associated with a magnesium ion (Mg(2+)) deficit in the serum or brain. However, the mechanisms regulating the roles of Mg(2+) in the pathologic condition of AD remain unknown. We studied whether brain Mg(2+) can decrease β-amyloid (Aβ) deposition and ameliorate the cognitive decline in a model of AD, the APPswe/PS1DE9 transgenic (Tg) mouse. We used a recently developed compound, magnesium-L-threonate (MgT), for a treatment that resulted in enhanced clearance of Aβ in an anterior pharynx-defective (APH)-1α/-1β-dependent manner...
December 2015: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Wei Li, Jia Yu, Yong Liu, Xiaojie Huang, Nashat Abumaria, Ying Zhu, Xian Huang, Wenxiang Xiong, Chi Ren, Xian-Guo Liu, Dehua Chui, Guosong Liu
BACKGROUND: Profound synapse loss is one of the major pathological hallmarks associated with Alzheimer's disease, which might underlie memory impairment. Our previous work demonstrates that magnesium ion is a critical factor in controlling synapse density/plasticity. Here, we tested whether elevation of brain magnesium, using a recently developed compound (magnesium-L-threonate, MgT), can ameliorate the AD-like pathologies and cognitive deficits in the APPswe/PS1dE9 mice, a transgenic mouse model of Alzheimer's disease...
2014: Molecular Brain
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