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1.
Andrey G Taranukhin Elena Y Taranukhina Pirjo Saransaari Irina M Podkletnova Markku Pelto-Huikko Simo S Oja 《Journal of biomedical science》2010,17(Z1):S12
Background
Acute ethanol administration leads to massive apoptotic neurodegeneration in the developing central nervous system. We studied whether taurine is neuroprotective in ethanol-induced apoptosis in the mouse cerebellum during the postnatal period.Methods
The mice were divided into three groups: ethanol-treated, ethanol+taurine-treated and controls. Ethanol (20% solution) was administered subcutaneously at a total dose of 5 g/kg (2.5 g/kg at time 1 h and 2.5 g/kg at 3 h) to the ethanol and ethanol+taurine groups. The ethanol+taurine group also received two injections of taurine (1 g/kg each, at time zero and at 4 h). To estimate apoptosis, immunostaining for activated caspase-3 and TUNEL staining were made in the mid-sagittal sections containing lobules I-X of the cerebellar vermis at 12 or 8 hours after the first taurine injection. Changes in the blood taurine level were monitored at each hour by reverse-phase high-performance liquid chromatography (HPLC).Results
Ethanol administration induced apoptosis of Purkinje cells on P4 in all cerebellar lobules, most extensively in lobules IX and X, and on P7 increased the number of activated caspase-3-immunoreactive and TUNEL-positive cells in the internal layer of the cerebellum. Administration of taurine significantly decreased the number of activated caspase-3-immunoreactive and TUNEL-positive cells in the internal layer of the cerebellum on P7, but had no effect on Purkinje cells in P4 mice. The high initial taurine concentration in blood of the ethanol+taurine group diminished dramatically during the experiment, not being different at 13 h from that in the controls.Conclusions
We conclude that the neuroprotective action of taurine is not straightforward and seems to be different in different types of neurons and/or requires prolonged maintenance of the high taurine concentration in blood plasma.2.
Background
Taurine and zinc exert neurotrophic effects in the central nervous system. Current studies demonstrate that Na+/Cl- dependent neurotransmitter transporters, similar to that of taurine, are modulated by micromolar concentrations of zinc. This study examined the effect of zinc sulfate ex vivo on [3H]taurine transport in goldfish retina.Methods
Isolated cells were incubated in Ringer with zinc (0.1–100 µM). Taurine transport was done with 50 nM [3H]taurine or by isotopic dilution with taurine (0.001–1 mM) and 50 nM [3H]taurine.Results
Zinc reduced the capacity of taurine transport without changes in affinity, and caused a noncompetitive inhibition of high affinity taurine transport, with an EC50= 0.072 µM. The mechanism by which zinc affects taurine transport is unknown at the present.Conclusions
There may be a binding site of zinc in the transporter that affects union or translocation of taurine, or possibly the formation of taurine-zinc complexes, rather than free zinc, could affect the operation of the transporter.3.
Jiancheng Yang Gaofeng Wu Ying Feng Qiufeng Lv Shumei Lin Jianmin Hu 《Journal of biomedical science》2010,17(Z1):S9
Background
It has been demonstrated that taurine is one of the most abundant free amino acids in the male reproductive system, and can be biosynthesized by male reproductive organs. But the effect of taurine on male reproduction is poorly understood.Methods
Taurine and β-alanine (taurine transport inhibitor) were offered in water to male rats of different ages. The effects of taurine on reproductive hormones, testis marker enzymes, antioxidative ability and sperm quality were investigated.Results
The levels of T and LH were obviously increased by taurine supplementation in rats of different ages, and the level of E was also significantly elevated in baby rats. The levels of SOD, ACP, SDH and NOS were obviously increased by taurine administration in adult rats, but the levels of AKP, AST, ALT and NO were significantly decreased. The levels of SOD, ACP, LDH, SDH, NOS, NO and GSH were significantly elevated by taurine administration in aged rats, but the levels of AST and ALT were significantly decreased. The motility of spermatozoa was obviously increased by taurine supplement in adult rats. The numbers and motility of spermatozoa, the rate of live spermatozoa were significantly increased by taurine supplement in aged rats.Conclusions
The present study demonstrated that a taurine supplement could stimulate the secretion of LH and T, increase the levels of testicular marker enzymes, elevate testicular antioxidation and improve sperm quality. The results imply that taurine plays important roles in male reproduction especially in aged animals.4.
Background
The present study elucidates the protective potential of bromelain against dichlorvos intoxication in mice brains. Dichlorvos induces the oxidative stress by disproportionating the balance between free radicals generation and their scavenging in neurons which leads to neuronal degeneration.Methods
In this study, mice were divided into four groups-group I (control), group II (dichlorvos treated), group III (bromelain treated) and group IV (exposed to both bromelain and dichlorvos both).Results
Dichlorvos treatment increased the levels of thiobarbituric acid reactive substances (TBARS) and protein carbonyl content (PCC) which indicate the increased oxidative stress. Meanwhile, brain endogenous antioxidants and cholinesterases level was decreased after dichlorvos exposure. Levels of TBARS and PCC decreased whereas cholinesterases level was recorded to be elevated after bromelain exposure.Conclusion
Bromelain offered neuroprotection by decreasing oxidative stress and augmenting cholinesterases in mice brains. This study highlights the invulnerability of bromelain against oxidative and cholinergic deficits in mice brains.5.
Mengjuan Liu Jiaqi Wang Hongping Tang Li Fan Liang Zhao Hai-Bin Wang Yan Zhou Wen-Song Tan 《Biotechnology letters》2018,40(11-12):1487-1493
Objective
To explore the impact of taurine on monoclonal antibody (mAb) basic charge variants in Chinese hamster ovary (CHO) cell culture.Results
In fed-batch culture, adding taurine in the feed medium slightly increased the maximum viable cell density and mAb titers in CHO cells. What’s more, taurine significantly decreased the lysine variant and oxidized variant levels, which further decreased basic variant contents from 32 to 27%. The lysine variant content in the taurine culture was approximately 4% lower than that in control condition, which was the main reason for the decrease in basic variants. Real-time PCR and cell-free assay revealed that taurine played a critical role in the upregulation of relative basic carboxypeptidase and stimulating extracellular basic carboxypeptidase activities.Conclusion
Taurine exhibits noticeable impact on lower basic charge variants, which are mainly due to the decrease of lysine variant and oxidized protein variants.6.
J. Joseph Sahaya Rajan T. Chinnappan Santiago R. Singaravel S. Ignacimuthu 《Biotechnology letters》2016,38(4):689-700
Objectives
Involvement of the outer membrane protein C (OmpC) of Escherichia coli in neurodegeneration was investigated using a mouse model.Results
OmpC formed protease-resistant fibres that exhibited the diagnostic features of an amyloid. The spectral shift in the Congo Red and the thioflavin T assays produced features similar to neurotoxic peptides. Intramuscular administration of OmpC in mice resulted in spongiform neurodegeneration of the brain through calcium-dependent apoptosis and also showed upregulation of apoptosis related genes. Immunolocalization of OmpC in brain demonstrated the direct involvement of the porin in neurodegeneration and formation of spongiform encephalopathy.Conclusion
We have demonstrated the ability of OmpC of E. coli to induce neurodegeneration in mice.7.
Background
Taurine is one of the most abundant free amino acids especially in excitable tissues, with wide physiological actions. Chronic supplementation of taurine in drinking water to mice increases brain excitability mainly through alterations in the inhibitory GABAergic system. These changes include elevated expression level of glutamic acid decarboxylase (GAD) and increased levels of GABA. Additionally we reported that GABAA receptors were down regulated with chronic administration of taurine. Here, we investigated pharmacologically the functional significance of decreased / or change in subunit composition of the GABAA receptors by determining the threshold for picrotoxin-induced seizures. Picrotoxin, an antagonist of GABAA receptors that blocks the channels while in the open state, binds within the pore of the channel between the β2 and β3 subunits. These are the same subunits to which GABA and presumably taurine binds.Methods
Two-month-old male FVB/NJ mice were subcutaneously injected with picrotoxin (5 mg kg-1) and observed for a) latency until seizures began, b) duration of seizures, and c) frequency of seizures. For taurine treatment, mice were either fed taurine in drinking water (0.05%) or injected (43 mg/kg) 15 min prior to picrotoxin injection.Results
We found that taurine-fed mice are resistant to picrotoxin-induced seizures when compared to age-matched controls, as measured by increased latency to seizure, decreased occurrence of seizures and reduced mortality rate. In the picrotoxin-treated animals, latency and duration were significantly shorter than in taurine-treated animas. Injection of taurine 15 min before picrotoxin significantly delayed seizure onset, as did chronic administration of taurine in the diet. Further, taurine treatment significantly increased survival rates compared to the picrotoxin-treated mice.Conclusions
We suggest that the elevated threshold for picrotoxin-induced seizures in taurine-fed mice is due to the reduced binding sites available for picrotoxin binding due to the reduced expression of the beta subunits of the GABAA receptor. The delayed effects of picrotoxin after acute taurine injection may indicate that the two molecules are competing for the same binding site on the GABAA receptor. Thus, taurine-fed mice have a functional alteration in the GABAergic system. These include: increased GAD expression, increased GABA levels, and changes in subunit composition of the GABAA receptors. Such a finding is relevant in conditions where agonists of GABAA receptors, such as anesthetics, are administered.8.
Background
Disruption to the blood brain barrier (BBB) is a leading factor associated with the development of postoperative cognitive dysfunction (POCD). Despite this, the underlying mechanism by which BBB disruption promotes POCD in the elderly population has not yet been not fully elucidated.Results
In this study, we established a POCD mice model using isoflurane, and observed the highly expressed occludin and claudin 5 in brain tissues concomitant with the increased enrichment of CD4 positive cells and NK cells in the hippocampus of POCD mice compared to normal and non-POCD control.Conclusions
Our data suggests that peripheral immune cells may participate in the inflammatory reaction within the hippocampus, following the administration of anesthesia via inhalation with the destruction of the blood-brain barrier.9.
Tie-juan Shao Zhi-xing He Zhi-jun Xie Hai-chang Li Mei-jiao Wang Cheng-ping Wen 《Metabolomics : Official journal of the Metabolomic Society》2016,12(4):70
Introduction
The differences in fecal metabolome between ankylosing spondylitis (AS)/rheumatoid arthritis (RA) patients and healthy individuals could be the reason for an autoimmune disorder.Objectives
The study explored the fecal metabolome difference between AS/RA patients and healthy controls to clarify human immune disturbance.Methods
Fecal samples from 109 individuals (healthy controls 34, AS 40, and RA 35) were analyzed by 1H NMR spectroscopy. Data were analyzed with principal component analysis (PCA) and orthogonal projection to latent structure discriminant (OPLS-DA) analysis.Results
Significant differences in the fecal metabolic profiles could distinguish AS/RA patients from healthy controls but could not distinguish between AS and RA patients. The significantly decreased metabolites in AS/RA patients were butyrate, propionate, methionine, and hypoxanthine. Significantly increased metabolites in AS/RA patients were taurine, methanol, fumarate, and tryptophan.Conclusion
The metabolome variations in feces indicated AS and RA were two homologous diseases that could not be distinguished by 1H NMR metabolomics.10.
11.
12.
Abdeslem El Idrissi Xin Yan Francoise Sidime William L’Amoreaux 《Journal of biomedical science》2010,17(Z1):S8
Background
The fragile X mouse model shows an increase in seizure susceptibility, indicating an involvement of the GABAergic system via an alteration in cellular excitability. In the brain, we have previously described a reduction in GABAA receptor expression as a likely basis for this susceptibility. In the brains of fragile X mice, this reduction in receptor expression culminates with a concomitant increase in the expression of glutamic acid decarboxylase (GAD), the enzyme responsible for GABA synthesis. Further, voltage-sensitive calcium channel expression is reduced in the pancreas of the fragile X mouse. Since there are considerable similarities in the GABAergic system in the brain and pancreas, we evaluated the protective role of taurine in pancreatic islet development in both wild type (WT) and fragile X mice (KO).Methods
One-month-old FVB/NJ males or age-matched fmr1-knockout (KO) mice were supplemented with taurine in drinking water (0.05% w/v) for four weeks. Age-matched controls were fed water only for the same duration. At four weeks, mice were sacrificed and pancreases processed for histology and immunohistochemical studies on changes of insulin, glucagon and somatostatin expression. Additional mice were subjected to a glucose tolerance test.Results
Taurine treatment resulted in a significant increase in the number and size of islets. WT taurine-fed mice, slightly hypoglycemic prior to glucose injection, showed significantly reduced plasma glucose at 30 min post-injection when compared to control mice. KO mice had normal baseline plasma glucose concentration; however, following glucose injection they had higher plasma glucose levels at 30 min when compared to controls. Supplementation of taurine to KO mice resulted in reduced baseline levels of plasma glucose. After glucose injection, the taurine-fed KO mice had reduced plasma glucose at 30 min compared to KO. Concomitant with the increased islets size and glucose tolerance observed in taurine-fed mice there was an increase in insulin, glucagon and somatostatin immunoreactivity in the islets of WT mice. In the KO mice however, insulin levels were not affected whereas glucagon and somatostatin levels were reduced. Exocytosis of these hormones is calcium-dependent, therefore any exacerbation of calcium homeostasis could affect hormone release. We found the expression of the voltage sensitive calcium channels (VSCC) is drastically reduced in the pancreas of fragile X mice.Conclusions
During early development, the VSCC play an important role in calcium-dependent gene expression. Since these channels are also involved in depolarization and calcium-mediated vesicular release of neurotransmitters and pancreatic hormones, alterations in the expression of VSCC not only will affect calcium-mediated gene expression but also hormonal and neurotransmitter release creating therefore a neuroendocrine perturbation in the fragile X that may potentially affect other organ systems. We find that in the fragile X mouse, taurine treatment may partially restore functionality of the neuro-endocrine pancreas.13.
Li Li Chang-Sheng Wu Guan-Mei Hou Ming-Zhe Dong Zhen-Bo Wang Yi Hou Heide Schatten Gui-Rong Zhang Qing-Yuan Sun 《Reproductive biology and endocrinology : RB&E》2018,16(1):110
Background
Diabetes induces many complications including reduced fertility and low oocyte quality, but whether it causes increased mtDNA mutations is unknown.Methods
We generated a T2D mouse model by using high-fat-diet (HFD) and Streptozotocin (STZ) injection. We examined mtDNA mutations in oocytes of diabetic mice by high-throughput sequencing techniques.Results
T2D mice showed glucose intolerance, insulin resistance, low fecundity compared to the control group. T2D oocytes showed increased mtDNA mutation sites and mutation numbers compared to the control counterparts. mtDNA mutation examination in F1 mice showed that the mitochondrial bottleneck could eliminate mtDNA mutations.Conclusions
T2D mice have increased mtDNA mutation sites and mtDNA mutation numbers in oocytes compared to the counterparts, while these adverse effects can be eliminated by the bottleneck effect in their offspring. This is the first study using a small number of oocytes to examine mtDNA mutations in diabetic mothers and offspring.14.
Ray O. Bahado-Singh Stewart F. Graham BeomSoo Han Onur Turkoglu James Ziadeh Rupasri Mandal Anil Er David S. Wishart Philip L. Stahel 《Metabolomics : Official journal of the Metabolomic Society》2016,12(6):100
Introduction
Traumatic brain injury (TBI) is physical injury to brain tissue that temporarily or permanently impairs brain function.Objectives
Evaluate the use of metabolomics for the development of biomarkers of TBI for the diagnosis and timing of injury onset.Methods
A validated model of closed injury TBI was employed using 10 TBI mice and 8 sham operated controls. Quantitative LC–MS/MS metabolomic analysis was performed on the serum.Results
Thirty-six (24.0 %) of 150 metabolites were altered with TBI. Principal component analysis (PCA) and Partial least squares discriminant analysis (PLS-DA) analyses revealed clear segregation between TBI versus control sera. The combination of methionine sulfoxide and the lipid PC aa C34:4 accurately diagnosed TBI, AUC (95 % CI) 0.85 (0.644–1.0). A combination of metabolite markers were highly accurate in distinguishing early (4 h post TBI) from late (24 h) TBI: AUC (95 % CI) 1.0 (1.0–1.0). Spermidine, which is known to have an antioxidant effect and which is known to be metabolically disrupted in TBI, was the most discriminating biomarker based on the variable importance ranking in projection (VIP) plot. Several important metabolic pathways were found to be disrupted including: pathways for arginine, proline, glutathione, cysteine, and sphingolipid metabolism.Conclusion
Using serum metabolomic analysis we were able to identify novel putative serum biomarkers of TBI. They were accurate for detecting and determining the timing of TBI. In addition, pathway analysis provided important insights into the biochemical mechanisms of brain injury. Potential clinical implications for diagnosis, timing, and monitoring brain injury are discussed.15.
N. Cesbron A.-L. Royer Y. Guitton A. Sydor B. Le Bizec G. Dervilly-Pinel 《Metabolomics : Official journal of the Metabolomic Society》2017,13(8):99
Introduction
Collecting feces is easy. It offers direct outcome to endogenous and microbial metabolites.Objectives
In a context of lack of consensus about fecal sample preparation, especially in animal species, we developed a robust protocol allowing untargeted LC-HRMS fingerprinting.Methods
The conditions of extraction (quantity, preparation, solvents, dilutions) were investigated in bovine feces.Results
A rapid and simple protocol involving feces extraction with methanol (1/3, M/V) followed by centrifugation and a step filtration (10 kDa) was developed.Conclusion
The workflow generated repeatable and informative fingerprints for robust metabolome characterization.16.
Andrew T. McKenzie Sarah Moyon Minghui Wang Igor Katsyv Won-Min Song Xianxiao Zhou Eric B. Dammer Duc M. Duong Joshua Aaker Yongzhong Zhao Noam Beckmann Pei Wang Jun Zhu James J. Lah Nicholas T. Seyfried Allan I. Levey Pavel Katsel Vahram Haroutunian Eric E. Schadt Brian Popko Patrizia Casaccia Bin Zhang 《Molecular neurodegeneration》2017,12(1):82
17.
Background
Several molecular and cellular processes in the vertebrate brain exhibit differences between males and females, leading to sexual dimorphism in the formation of neural circuits and brain organization. While studies on large-scale brain networks provide ample evidence for both structural and functional sex differences, smaller-scale local networks have remained largely unexplored. In the current study, we investigate sexual dimorphism in cortical dynamics by means of spontaneous Up/Down states, a type of network activity that is exhibited during slow-wave sleep, quiet wakefulness, and anesthesia and is thought to represent the default activity of the cortex.Methods
Up state activity was monitored by local field potential recordings in coronal brain slices of male and female mice across three ages with distinct secretion profiles of sex hormones: (i) pre-puberty (17–21 days old), (ii) 3–9 adult (months old), and (iii) old (19–24 months old).Results
Female mice of all ages exhibited longer and more frequent Up states compared to aged-matched male mice. Power spectrum analysis revealed sex differences in the relative power of Up state events, with female mice showing reduced power in the delta range (1–4 Hz) and increased power in the theta range (4–8 Hz) compared to male mice. No sex differences were found in the characteristics of Up state peak voltage and latency.Conclusions
The present study revealed for the first time sex differences in intracortical network activity, using an ex vivo paradigm of spontaneously occurring Up/Down states. We report significant sex differences in Up state properties that are already present in pre-puberty animals and are maintained through adulthood and old age.18.
Background
Thiamine is an essential cofactor associated with several enzymes in energy metabolism and its deficiency may lead to neurological deficits. Current research evaluated the biochemical and molecular changes in TCA cycle enzymes using the mitochondrial fraction of the brain following thiamine deficiency (TD) in mice.Methods
The investigation was carried out on Swiss mice (6-8 week old) allocated into three groups. First group was control; second and third group were made thiamine deficient for 8 and 10 days.Results
Current study showed that alpha-ketoglutarate dehydrogenase (KGDHC) (thiamine-dependent enzyme) level found to be significantly reduced in experimental groups as compared to control group. In comparison to control group, a significant decrease in the succinate dehydrogenase (SDH) activity was calculated in group II and group III (p<0.0001) mice. Diminished enzymatic activity of fumarase and MDH enzyme in thiamine deficient groups exposed for 8 and 10 days was calculated as compared to control group. The expression analysis of different genes governing TCA cycle enzymes in different experimental groups showed that there was a negotiable change in the expression of fumarase and DLD (dihydrolipoyl dehydrogenase- E3 subunit of KGDHC) whereas a declined in the expression of SDH and two subunits of KGDHC i.e. OGDH (2-oxoglutarate dehydrogenase- E1 subunit of KGDHC) and DLST (dihydrolipoyllysine-residue succinyltransferase- E2 subunit of KGDHC) was observed as compared to control group.Conclusions
Hence, current findings strongly entail that TD promotes alteration in energy metabolism in brain mitochondria which will decline the neuronal progression which may lead to neurodegenerative diseases such as Alzheimer’s diseases.19.
Hui Yang Wenliang Ji Ming Guan Shilei Li Yangyang Zhang Zhenwen Zhao Lanqun Mao 《Metabolomics : Official journal of the Metabolomic Society》2018,14(4):50
Introduction
In-situ detection and in particular comprehensive analysis of small molecule metabolites (SMMs, m/z?<?500) using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI MSI) remain a challenge, mainly due to ion suppression effects from more abundant molecules in tissue section like lipids.Objective
A strategy based on organic washes to remove most ionization-suppressing lipids from tissue section was firstly explored for improved analysis of SMMs by MALDI MSI.Methods
The tissue sections after rinse with different organic solvents were analyzed by MALDI MSI, and the results were compared for the optimized washing conditions.Results
The rinse with chloroform for 15 s at ??20 °C significantly removed most glycerophospholipids and glycerolipids from tissue section. Consequentially, ATP-related energy metabolites, amino acids and derivatives, glucose derivatives, glycolysis pathway metabolites and other SMMs were able to be well-visualized with enhanced ion intensity and good reproducibility. The organic washes-based MALDI MSI was applied to the metabolic pathway analysis in rat brain following status epilepticus (SE) model, which was, as far as we know, the first report about in-situ detection of a broad range of metabolites in the model of SE by MALDI MSI technique. The alterations of cyclic adenosine monophosphate (cyclic AMP), inosine, glutamine, glutathione, taurine and spermine during SE were observed.Conclusion
A simple organic washing protocol enables comprehensive analysis of tissue SMMs in MALDI MSI by removing ionization-suppressing lipids. The application in the SE model indicates that MALDI MSI analysis potentially provides new insight for understanding the disease mechanism.20.