Time course expression of glial fibrillary acidic protein by implanted astrocytes after intracranial grafting of immature and mature brain tissue.
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Animals↗
Biomedical subjects
N Baumann
Publications and source records attributed to N Baumann.
Transplantation of oligodendrocytes in the newborn mouse brain: extension of myelination by transplanted cells. Anatomical study.
The shiverer model allows for the immunocytochemical staining of the patches of myelin formed by transplanted oligodendrocytes from a normal newborn mouse. Fragments of the olfactory bulb were transplanted into various parts of the brain to place the myelinating cells in different anatomical conditions. Whole brains were horizontally sectioned in order to study the full pattern of migration and myelination of the grafted oligodendrocytes. Transplanted oligodendrocytes were capable of short and long distance migration before their differentiation. Long distance migration occurred in the caudal as well as in the rostral direction and into the contralateral part of the brain through the commissures. The patches of immunoreactive myelin were mainly found in the large myelinated bundles: corpus callosum, internal capsule, fimbria-fornix, medial lemniscus, cerebellar peduncles and spinal cord funiculi. Some sites of migration indicate that oligodendrocytes followed at least two different axonal pathways successively. The thalamic area which contained numerous patches could be a place where oligodendrocytes switch from one fasciculus to another.
Animals↗
Adult adrenoleukodystrophy: a sporadic case?
This is a report of a case of the adult cerebral form of X-linked ALD. The 27-year-old patient presented with psychiatric disturbances. NMR was performed and compared to CT scan to define cerebral demyelination. The level of hexacosanoate was found to be increased in the patient's serum. Biochemical analysis of the patient's mother's serum and cultured fibroblasts and of serum samples from 10 other members of the family who could have been carriers of this X-linked disease, produced negative results. Hence, it is most likely that this case has occurred sporadically. HLA determination revealed the DR2 antigen which is often associated with multiple sclerosis.
Adrenoleukodystrophy↗
Immunohistochemical, biochemical and electron microscopic analysis of myelin formation in the central nervous system of myelin deficient (mld) mutant mice.
Myelin deficiency (mld) is an autosomal recessive mutation in mice and is considered to be allelic to the shiverer (shi) mutation. Mld mice are characterized by hypomyelination of the central nervous system (CNS). They show typical symptoms such as tremor, tonic convulsion and ataxic movement. Subcellular fractionation of the CNS revealed that the MBP bands were greatly decreased in the P2A (myelin) fraction and the total content of myelin basic protein (MBP) was much lower than that in the control in all parts of the CNS. Sections from mld mice were examined by immunohistochemical tests with MBP antiserum, and a mosaic expression of MBP was found in the myelin of the mld mice. Since the major dense line is considered to be composed mainly of MBP, we investigated the myelin of mld mice by electron microscopy and found that there were 3 types of myelin: (1) a normal type compact myelin with a major dense line, (2) a shiverer-type myelin with no major dense line, and (3) a mixed-type myelin, in which within a myelin lamella the major dense line abruptly changes to cytoplasm of oligodendrocytes.
2',3'-Cyclic-Nucleotide Phosphodiesterases↗
Arachidonoyl-coenzyme A synthetase and nonspecific acyl-coenzyme A synthetase activities in purified rat brain microvessels.
Purified rat brain microvessels were prepared to demonstrate the occurrence of acyl-CoA (EC 6.2.1.3) synthesis activity in the microvasculature of rat brain. Both arachidonoyl-CoA and palmitoyl-CoA synthesis activities showed an absolute requirement for ATP and CoA. This activity was strongly enhanced by magnesium chloride and inhibited by EDTA. The apparent Km values for acyl-CoA synthesis by purified rat brain microvessels were 4.0 microM and 5.8 microM for palmitic acid and arachidonic acid, respectively. The apparent Vmax values were 1.0 and 1.5 nmol X min-1 X mg protein-1 for palmitic acid and arachidonic acid, respectively. Cross-competition experiments showed inhibition of radiolabelled arachidonoyl-CoA formation by 15 microM unlabelled arachidonic acid, with a Ki of 7.1 microM, as well as by unlabelled docosahexaenoic acid, with a Ki of 8.0 microM. Unlabelled palmitic acid and arachidic acid had no inhibitory effect on arachidonoyl-CoA synthesis. In comparison, radiolabelled palmitoyl-CoA formation was inhibited competitively by 15 microM unlabelled palmitic acid, with a Ki of 5.0 microM and to a much lesser extent by arachidonic acid (Ki, 23 microM). The Vmax of palmitoyl-CoA formation obtained on incubation in the presence of the latter fatty acids was not changed. Unlabelled arachidic acid and docosahexaenoic acid had no inhibitory effect on palmitoyl-CoA synthesis. Both arachidonoyl-CoA and palmitoyl-CoA synthesis activities were thermolabile. Arachidonoyl-CoA formation was inhibited by 75% after 7 min at 40 degrees C whereas a 3-min heating treatment was sufficient to produce the same relative inhibition of palmitoyl-CoA synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Acyl Coenzyme A↗
Transplantation of human embryonic oligodendrocytes into shiverer brain.
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Animals↗
[Binding of immunoglobulins of the cerebrospinal fluid of multiple sclerosis patients to oligodendrocytes in culture].
There is often, in multiple sclerosis (MS) an intrathecal synthesis of immunoglobulin G (IgG) with an electrophoretic oligoclonal pattern. The target of those IgG, as well as their possible pathogenic role in the demyelinating process remain unknown and have led to many controversies. We have tested the hypothesis of an oligodendroglial target for those Ig, using a double labelling indirect immunofluorescent assay. Cerebrospinal fluid (CSF) Ig were collected from 28 MS patients (with either progressive or remitting-relapsing disease) and 25 patients with other neurological diseases. Ig binding has been tested on rat and human oligodendrocytes, isolated on a Percoll gradient and maintained 24 to 48 hours in culture. In our experimental conditions, we have never been able to detect any specific binding of MS CSF Ig on those oligodendrocytes, identified by double labelling immunofluorescence with an anti-galactocerebroside antibody.
Animals↗
[Intracerebral transplantation of oligodendrocytes in mice].
We describe in this paper experiments in which oligodendrocytes (from newborn mouse, human embryonic brain, or isolated from adult rat brain) have been transplanted into the brain of the newborn mouse. Experimental conditions (Shiverer model) allowed the detection of myelin formed by transplanted oligodendrocytes into the Shiverer brain. The transplanted oligodendrocytes have been shown to survive, migrate over long distances and myelinate host axons. The maturation of transplanted oligodendrocytes depends upon the age of the brain tissue in which they differentiate.
Animals↗
Neuronal expression of mutations affecting primarily glia in the mouse: studies in the dysmyelinated and convulsive mutant quaking.
1. Various aspects of the noradrenergic system in the brain of the dysmyelinating convulsive mutant mice quaking have been examined. 2. Determination of the endogenous contents of noradrenaline and its metabolite 3-methoxy 4-hydroxyphenyl-ethyleneglycol (MOPEG), as well as measurement of the electrically-evoked release of (3H)-noradrenaline shows an increased noradrenergic activity in the brain of the mutants, when compared to non convulsive controls of the same strain. 3. Ontogenic development of alpha adrenergic receptors indicate that an increased density of alpha-2 sites precedes the appearance of the first convulsions by approximately one week. 4. Anatomical determination of the number of noradrenergic neuronal cell bodies in the locus coeruleus shows a hyperplasia of this nucleus in the mutants. 5. Electrolytic coagulation of the locus coeruleus inhibits the convulsions of the quaking mice. 6. These results suggest that an alteration of the embryonic differentiation of the locus coeruleus, which gives rise to the majority of brain noradrenergic neurons, provokes a hyperactivity of this neuronal system, thereby triggering the convulsions of the quaking mutant mice. 7. The possible involvement of other neurotransmitter systems in the convulsions of these mutants, together with the nature of the relationship between neuronal abnormalities and dysmyelination phenomenon, are discussed.
Animals↗
Modifications of sphingomyelin and phosphatidylcholine metabolism by tricyclic antidepressants and phenothiazines.
Phenothiazines and tricyclic antidepressants, when added to culture medium, gave rise in several types of cells (C6 rat glioma cells and human fibroblasts), to a decrease in lysosomal sphingomyelinase activity. The effect of chlorpromazine and desipramine was dose dependent, and was observed after 3 hours of incubation with the drugs at concentrations ranging between 1 and 10 microM. In C6 glioma cell cultures, the decrease in sphingomyelinase activity was related to the clinical effectiveness of phenothiazines, tricyclic antidepressants and derivatives. Incorporation of (choline-14C) sphingomyelin showed that the metabolic pathway implying the synthesis of phosphatidylcholine from the hydrolysis of sphingomyelin and/or transfer of phosphorylcholine to phosphatidylcholine was also partially reduced.
Animals↗
Lithium distribution in the brain of normal mice and of "quaking" dysmyelinating mutants.
Using nuclear reaction 6Li(n, alpha)3H and dielectric detectors, we have studied the distribution of Li in the brain of adult mice, following Li treatment of the animals. Two strains of animals were used in parallel: "quaking" dysmyelinating mutants and normally myelinated controls. The distribution appeared to be sharply regionalized in the brain of the normal mice (higher Li concentration in the gray rather than in the white matter, with the area postrema being particularly Li rich). In contrast, the Li distribution was practically homogeneous in the brain of the quaking dysmyelinating mutants, with a mean Li concentration comparable to that in the gray matter of the controls. The present method of Li detection has made it possible to estimate the Li equilibrium potentials (nerve cells with regard to plasma) in the different brain substructures. The results are consistent with (a) Li being actively extruded from nerve cells in all the cases and (b) myelination decreasing the relative importance of the passive component of Li transport in the nerve cells, as compared with the active component.
Animals↗
Schwann cell differentiation in vitro: extracellular matrix deposition and interaction.
Neonatal rat Schwann cells isolated in culture proliferate slowly and do not form a basement membrane although they express laminin continuously. We demonstrate here that isolated Schwann cells express other basement membrane components, including entactin and heparan sulfate proteoglycan. Treatment with ascorbate, and to a lesser extent with cyclic adenosine 3',5'-monophosphate, modulates the synthesis of extracellular matrix components by cultured Schwann cells. After this treatment, fibronectin and collagen type IV are detected on the Schwann cell surface, which form, with the other components, a membrane-bound extracellular matrix. Electron microscopy shows that these elements are organized in a filamentous matrix which resembles a basement membrane and may be a precursor form of a basement membrane. We also show the effect of complete basement membrane matrices on Schwann cell behavior in culture. These matrices support Schwann cell proliferation in both serum-containing and serum-free media. The extracellular matrix from endothelial cells mimics fibronectin and induces a flat phenotype whereas the reconstituted basement membrane gel from the EHS tumor mimics laminin and allows an elongated phenotype. Thus, the basement membrane matrices interact with Schwann cells in vitro and may play an important role in Schwann cell proliferation in vivo.
Animals↗
Transplantations of newborn CNS fragments into the brain of shiverer mutant mice: extensive myelination by transplanted oligodendrocytes. II. Electron microscopic study.
As already demonstrated by immunohistochemistry, oligodendrocytes from newborn normal mice are able to survive, migrate and myelinate when transplanted into the newborn shiverer (shi/shi) mouse brain. The survival of the grafted cells and their interaction with the host brain were studied at different times after transplantation. Normal myelin was found in the host parenchyma basing our observation on the morphological difference between normal and shiverer myelin: the shiverer myelin deprived of major dense line appears uncompacted as compared to normal myelin. Myelin formed by transplanted oligodendrocytes was detected around the graft and, after immunohistochemical prelocalization, at considerable distance from the site of implantation. Normal and shiverer myelin were detected around axons adjacent to each other or around the same axon. These results confirm and extend at the ultrastructural level our previous data obtained by immunohistochemistry.
Animals↗
Modulation of alpha 1-and alpha 2-adrenoceptor binding sites in the brain of audiogenic seizure susceptible mice (DBA/2J).
The binding of [3H]dihydroalprenolol ([3H]DHA), [3H]prazosin and [3H]clonidine was assayed in whole brain and various brain regions of audiogenic seizure (AS) susceptible DBA/2J (D2) mice aged 10, 24 and 50 days (i.e. before, during and after their period of AS susceptibility, respectively) and in age-matched C57BL/6J (B6) controls. In whole brain, at 24 days, [3H]DHA binding was similar in the two strains, while the binding of [3H]prazosin and [3H]clonidine was significantly lowered in D2 mice. No difference could be detected in 10 and 50 day old mice with any of the ligands. Regional studies indicated an involvement of the cerebral cortex, the olfactory bulbs and the brain-stem. alpha- (but not beta-)adrenoceptor changes were concomitant with the AS susceptibility period. These changes were unevenly distributed in the brain of D2 mice; they suggest that alpha 1- and alpha 2-adrenoceptor subtypes might play different roles in the AS of the D2 mouse strain.
Acoustic Stimulation↗
Increased number of locus ceruleus noradrenergic neurons in the convulsive mutant quaking mouse.
Noradrenergic cell bodies in the locus ceruleus of the convulsive mutant quaking mouse and the control of the same strain were visualized using histofluorescence and tyrosine hydroxylase-like immunoreactivity. Cell counts performed with the two techniques gave closely similar results within each strain, indicating a 50% increase in the number of noradrenergic neurons in the midportion of the mutants' locus ceruleus when compared to the controls. This result gives histological support to the increased noradrenergic neurotransmission previously described in the brain of this mutant. Thus, the abnormally high activity of the noradrenergic system appears to be a primary effect of the mutation, associated with the convulsions of this animal model of epilepsy.
Adrenergic Fibers↗
Direct sensitive immunocharacterization of gangliosides on plastic thin-layer plates using peroxidase staining.
A technique for the immunocharacterization of gangliosides on thin-layer plates using a peroxidase-labelled anti-Ig antibody is described. The technique uses plastic plates and does not necessitate any transfer of the antigen onto nitrocellulose for immunodetection. Being extremely sensitive, it permits the characterization of gangliosides which cannot be detected by classical densitometric techniques and allows the detection of gangliosides even in trace amounts in ganglioside mixtures. It appears to be useful for the screening of monoclonal antibodies because of its rapidity. Its specificity was found to be analogous to other immunological techniques such as complement fixation and agglutination.
Antibody Specificity↗
Altered postnatal ontogeny of alpha 1- and alpha 2-adrenoceptor binding sites in the brain of a convulsive mutant mouse (quaking).
Binding assays of [3H]dihydroalprenolol ([3H]DHA), [3H]prazosin and [3H]clonidine have been performed on whole brain (minus cerebellum) homogenates of the convulsive mutant mice quaking (qk) and the controls of the same strain (C57BL/6J:B6). In 70-day-old mutants (which fully exhibit the qk convulsive phenotype), the binding of [3H]DHA to beta-adrenoceptor binding sites was not different from the controls, whereas the binding capacities of [3H]prazosin and [3H]clonidine to alpha 1-and alpha 2-adrenoceptor sites, respectively, were greatly enhanced. The biphasic ontogenic pattern of alpha 2-adrenoceptors had a greater amplitude in the brain of 30- to 90-day-old mutants than in the corresponding B6 controls. In mutants younger than 30 days or older than 90 days, the number of alpha 2-adrenoceptor sites was not modified. The number of alpha 1-adrenoceptor binding sites was increased in the brain of the mutants, only in animals older than 70 days. In younger mice, the postnatal modulation of alpha 1-adrenoceptor sites was identical to the controls. Regional studies were performed in 70-day-old mice. [3H]clonidine binding was increased in the brainstem of the mutants, and to a lesser extent in the cerebral cortex, while it was slightly diminished in the hypothalamic area. [3H]prazosin binding was also increased in the brainstem of the mutants, and decreased in the olfactory bulbs. Our results suggest that the convulsions of the qk mutants are selectively associated with modifications of alpha- and not beta-adrenoceptor binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Brain gangliosides of quaking and shiverer mutants: qualitative and quantitative changes of monosialogangliosides in the quaking brain.
Ganglioside compositions in the brains of the mutant mice quaking and shiverer were compared with those of their littermate controls, C57BL/6 and C3HSWV. Neither ganglioside content nor composition of shiverer brains differed from those of the control brains. Change in the ganglioside composition of the mutant brain from that of the control was observed only in the quaking mutant brain, in which monosialoganglioside GM1 was significantly reduced and GM4 was completely absent. The structures of the gangliosides were determined by negative ion fast atom bombardment mass spectrometry, and the GM3 and GM4 gangliosides in the quaking brain were found to be altered in regard to their long-chain base and fatty acid compositions when compared to the normal C57BL/6 brain.
Animals↗