scholarly journals Conversion of ethanolamine, monomethylethanolamine and dimethylethanolamine to choline-containing compounds by neurons in culture and by the rat brain

1989 ◽  
Vol 264 (2) ◽  
pp. 555-562 ◽  
Author(s):  
C Andriamampandry ◽  
L Freysz ◽  
J N Kanfer ◽  
H Dreyfus ◽  
R Massarelli
Keyword(s):  
Rat Brain ◽  
Primary Culture ◽  
De Novo ◽  
Water Soluble ◽  
Intraventricular Injection ◽  
Chick Embryos ◽  
Fetal Rat ◽  
Derivatives Of ◽  
The Brain

The incubation of neurons from chick embryos in primary culture with [3H]ethanolamine revealed the conversion of this base into monomethyl, dimethyl and choline derivatives, including the corresponding free bases. Labelling with [methyl-3H]monomethylethanolamine and [methyl-3H]dimethylethanolamine supported the conclusion that in chick neuron cultures, phosphoethanolamine appears to be the preferential substrate for methylation, rather than ethanolamine or phosphatidylethanolamine. The methylation of the latter two compounds, in particular that of phosphatidylethanolamine, was seemingly stopped at the level of their monomethyl derivatives. Fetal rat neurons in primary culture incubated with [3H]ethanolamine showed similar results to those observed with chick neurones. However, phosphoethanolamine and phosphatidylethanolamine and, to a lesser extent, free ethanolamine, appeared to be possible substrates for methylation reactions. The methylation of water-soluble ethanolamine compounds de novo was further confirmed by experiments performed in vivo by intraventricular injection of [3H]ethanolamine. Phosphocholine and the monomethyl and dimethyl derivatives of ethanolamine were detected in the brain 15 min after injection.

Thiamine transport in the central nervous system

1976 ◽  
Vol 230 (4) ◽  
pp. 1101-1107 ◽  
Author(s):  
R Spector
Keyword(s):  
Choroid Plexus ◽  
Intraventricular Injection ◽  
Simple Diffusion ◽  
Thiamine Transport ◽  
Choroid Plexuses ◽  
The Central Nervous System ◽  
The Brain ◽  
Thiamine Phosphates

Total thiamine (free thiamine and thiamine phosphates) transport into the cerebrospinal fluid (CSF), brain, and choroid plexus and out of the CSF was measured in rabbits. In vivo, total thiamine transport into CSF, choroid plexus, and brain was saturable. At the normal plasma total thiamine concentration, less than 5% of total thiamine entry into CSF, choroid plexus, and brain was by simple diffusion. The relative turnovers of total thiamine in choroid plexus, whole brain, and CSF were 5, 2, and 14% per h, respectively, when measured by the penetration of 35S-labeled thiamine injected into blood. From the CSF, clearance of [35S]thiamine relative to mannitol was not saturable after the intraventricular injection of various concentrations of thiamine. However, a portion of the [35S]thiamine cleared from the CSF entered brain by a saturable mechanism. In vitro, choroid plexuses, isolated from rabbits and incubated in artificial CSF, accumulated [35S]thiamine against a concentration gradient by an active saturable process that did not depend on pyrophosphorylation of the [35S]thiamine. The [35S]thiamine accumulated within the choroid plexus in vitro was readily released. These results were interpreted as showing that the entry of total thiamine into the brain and CSF from blood is regulated by a saturable transport system, and that the locus of this system may be, in part, in the choroid plexus.

scholarly journals In vivo assembly of tight junctions in fetal rat liver.

1975 ◽  
Vol 67 (2) ◽  
pp. 310-319 ◽  
Author(s):  
R Montesano ◽  
D S Friend ◽  
A Perrelet ◽  
L Orci
Keyword(s):  
Tight Junctions ◽  
De Novo ◽  
Early Stage ◽  
Fetal Life ◽  
Bile Canaliculi ◽  
Linear Arrays ◽  
Fetal Rat ◽  
Particle Aggregates ◽  
Fetal Rat Liver

Examination of glutaraldehyde-fixed, freeze-fractured livers from 14-15-day rat fetuses provided the basis for the following observations. Membrane particles align in otherwise poorly particulated areas of the presumptive pericanalicular plasma membrane (A face), frequently forming a discontinuous "honey-comb" network joining small particle islands. Even at this early stage, contiguous B-fracture faces contain furrows, rather than rows of pits, distinguishing the linear particle aggregates on the A face as developing tight junctions rather than gap junctions. Short segments of these linear arrays merge with smooth ridges clearly identifiable as segments of discontinuous tight junctions. With the continuing confluence of particulate and smooth ridge segments, mature tight junctions become fully appreciable. We conclude that tight junctions form de novo by the alignment and fusion of separate particles into beaded ridges which, in turn, become confluent and are transformed into continuous smooth ones. At 21 days of fetal life, most of the images of assembly have disappeared, and the liver reveals well-formed bile canaliculi sealed by mature tight junctions.

scholarly journals In Vivo Microdialysis of Endogenous and 13C-labeled TCA Metabolites in Rat Brain: Reversible and Persistent Effects of Mitochondrial Inhibition and Transient Cerebral Ischemia

Metabolites ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 204 ◽  
Author(s):  
Jesper F. Havelund ◽  
Kevin H. Nygaard ◽  
Troels H. Nielsen ◽  
Carl-Henrik Nordström ◽  
Frantz R. Poulsen ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Mitochondrial Dysfunction ◽  
Rat Brain ◽  
De Novo ◽  
Tricarboxylic Acid Cycle ◽  
Experimental Models ◽  
Transient Cerebral Ischemia ◽  
Metabolic Disturbances ◽  
Metabolic Marker

Cerebral micro-dialysis allows continuous sampling of extracellular metabolites, including glucose, lactate and pyruvate. Transient ischemic events cause a rapid drop in glucose and a rise in lactate levels. Following such events, the lactate/pyruvate (L/P) ratio may remain elevated for a prolonged period of time. In neurointensive care clinics, this ratio is considered a metabolic marker of ischemia and/or mitochondrial dysfunction. Here we propose a novel, sensitive microdialysis liquid chromatography-mass spectrometry (LC-MS) approach to monitor mitochondrial dysfunction in living brain using perfusion with 13C-labeled succinate and analysis of 13C-labeled tricarboxylic acid cycle (TCA) intermediates. This approach was evaluated in rat brain using malonate-perfusion (10–50 mM) and endothelin-1 (ET-1)-induced transient cerebral ischemia. In the malonate model, the expected changes upon inhibition of succinate dehydrogenase (SDH) were observed, i.e., an increase in endogenous succinate and decreases in fumaric acid and malic acid. The inhibition was further elaborated by incorporation of 13C into specific TCA intermediates from 13C-labeled succinate. In the ET-1 model, increases in non-labeled TCA metabolites (reflecting release of intracellular compounds) and decreases in 13C-labeled TCA metabolites (reflecting inhibition of de novo synthesis) were observed. The analysis of 13C incorporation provides further layers of information to identify metabolic disturbances in experimental models and neuro-intensive care patients.

scholarly journals α-Synuclein conformational strains spread, seed and target neuronal cells differentially after injection into the olfactory bulb

2019 ◽  
Vol 7 (1) ◽  
Author(s):  
Nolwen L. Rey ◽  
Luc Bousset ◽  
Sonia George ◽  
Zachary Madaj ◽  
Lindsay Meyerdirk ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
De Novo ◽  
Structural Features ◽  
Alpha Synuclein ◽  
Ample Evidence ◽  
Neuronal Connections ◽  
Wild Type Female ◽  
Culture Models ◽  
The Brain

AbstractAlpha-synuclein inclusions, the hallmarks of synucleinopathies, are suggested to spread along neuronal connections in a stereotypical pattern in the brains of patients. Ample evidence now supports that pathological forms of alpha-synuclein propagate in cell culture models and in vivo in a prion-like manner. However, it is still not known why the same pathological protein targets different cell populations, propagates with different kinetics and leads to a variety of diseases (synucleinopathies) with distinct clinical features. The aggregation of the protein alpha-synuclein yields different conformational polymorphs called strains. These strains exhibit distinct biochemical, physical and structural features they are able to imprint to newly recruited alpha-synuclein. This had led to the view that the clinical heterogeneity observed in synucleinopathies might be due to distinct pathological alpha-synuclein strains.To investigate the pathological effects of alpha-synuclein strains in vivo, we injected five different pure strains we generated de novo (fibrils, ribbons, fibrils-65, fibrils-91, fibrils-110) into the olfactory bulb of wild-type female mice. We demonstrate that they seed and propagate pathology throughout the olfactory network within the brain to different extents. We show strain-dependent inclusions formation in neurites or cell bodies. We detect thioflavin S-positive inclusions indicating the presence of mature amyloid aggregates.In conclusion, alpha-synuclein strains seed the aggregation of their cellular counterparts to different extents and spread differentially within the central nervous system yielding distinct propagation patterns. We provide here the proof-of-concept that the conformation adopted by alpha-synuclein assemblies determines their ability to amplify and propagate in the brain in vivo. Our observations support the view that alpha-synuclein polymorphs may underlie different propagation patterns within human brains.

scholarly journals The metabolism of [Me−14C]choline in the brain of the rat in vivo

1968 ◽  
Vol 110 (2) ◽  
pp. 201-206 ◽  
Author(s):  
G B Ansell ◽  
Sheila Spanner
Keyword(s):  
Water Soluble ◽  
Adult Rat ◽  
Free Choline ◽  
The Brain

[Me−14C]Choline was injected intracerebrally into the adult rat, and its uptake into the lipids and their water-soluble precursors in brain was studied. The radioactivity could be detected only in the choline-containing lipids and was confined to the base choline. The results indicated that initial phosphorylation of the free choline followed by the formation of CDP-choline and the subsequent transfer of the phosphorylcholine to a diglyceride is one of the principal routes by which choline lipids in brain are formed. Further evidence for this was obtained in experiments in which either phosphoryl[Me−14C]choline or [32P]orthophosphate was injected and the radioactivity in the choline-containing water-soluble and lipidbound components studied.

scholarly journals A Pachygyria-causing α-Tubulin Mutation Results in Inefficient Cycling with CCT and a Deficient Interaction with TBCB

2008 ◽  
Vol 19 (3) ◽  
pp. 1152-1161 ◽  
Author(s):  
Guoling Tian ◽  
Xiang-Peng Kong ◽  
Xavier H. Jaglin ◽  
Jamel Chelly ◽  
David Keays ◽  
...  
Keyword(s):  
De Novo Assembly ◽  
Structural Integrity ◽  
De Novo ◽  
Disease Phenotype ◽  
Tubulin Gene ◽  
Folding Intermediates ◽  
Diminished Capacity ◽  
The Brain ◽  
Dependent Interaction

The agyria (lissencephaly)/pachygyria phenotypes are catastrophic developmental diseases characterized by abnormal folds on the surface of the brain and disorganized cortical layering. In addition to mutations in at least four genes—LIS1, DCX, ARX and RELN—mutations in a human α-tubulin gene, TUBA1A, have recently been identified that cause these diseases. Here, we show that one such mutation, R264C, leads to a diminished capacity of de novo tubulin heterodimer formation. We identify the mechanisms that contribute to this defect. First, there is a reduced efficiency whereby quasinative α-tubulin folding intermediates are generated via ATP-dependent interaction with the cytosolic chaperonin CCT. Second, there is a failure of CCT-generated folding intermediates to stably interact with TBCB, one of the five tubulin chaperones (TBCA–E) that participate in the pathway leading to the de novo assembly of the tubulin heterodimer. We describe the behavior of the R264C mutation in terms of its effect on the structural integrity of α-tubulin and its interaction with TBCB. In spite of its compromised folding efficiency, R264C molecules that do productively assemble into heterodimers are capable of copolymerizing into dynamic microtubules in vivo. The diminished production of TUBA1A tubulin in R264C individuals is consistent with haploinsufficiency as a cause of the disease phenotype.

Methylation and expression of the Myo D1 determination gene

1990 ◽  
Vol 326 (1235) ◽  
pp. 277-284 ◽  
Keyword(s):  
De Novo ◽  
Cell Types ◽  
Model System ◽  
Parental Line ◽  
Molecular Control ◽  
Embryo Cells ◽  
End Stage ◽  
Derivatives Of

Mouse embryo cells induced to differentiate with the demethylating agent 5- azacytidine represent an excellent model system to investigate the molecular control of development. Clonal derivatives of 10T1/2 cells that have become determined to the myogenic or adipogenic lineages can be isolated from the multipotential parental line after drug treatment. These determined derivatives can be cultured indefinitely and will differentiate into end-stage phenotypes on appropriate stimulation. A gene called Myo D1, recently isolated from such a myoblast line, will confer myogenesis when expressed in 10T1/2 or other cell types (Davis et al. 1987). The cDNA for Myo D1 contains a large number of CpG sequences and the gene is relatively methylated in 10T1/2 cells and an adipocyte derivative, but is demethylated in myogenic derivatives. Myo D1 may therefore be subject to methylation control in vitro . On the other hand, preliminary observations suggest that Myo D1 is not methylated at CCGG sites in vivo so that a de novo methylation event may have occurred in vitro . These observations may have significance in the establishment of immortal cell lines and tumours.

Highly water-soluble derivatives of the anesthetic agent propofol: in vitro and in vivo evaluation of cyclic amino acid esters

2003 ◽  
Vol 20 (1) ◽  
pp. 17-26 ◽  
Author(s):  
Cosimo Altomare ◽  
Giuseppe Trapani ◽  
Andrea Latrofa ◽  
Mariangela Serra ◽  
Enrico Sanna ◽  
...  
Keyword(s):  
Amino Acid ◽  
Water Soluble ◽  
Anesthetic Agent ◽  
Amino Acid Esters ◽  
In Vivo Evaluation ◽  
Derivatives Of ◽  
Acid Esters
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