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F Lachapelle

Publications and source records attributed to F Lachapelle.

At least 37 records · Page 2Linked to original sources
PubMed1994

Cellular expression of an HMGCR promoter-CAT fusion gene in transgenic mouse brain: evidence for a developmental regulation in oligodendrocytes.

The HMGCR gene encodes the 3-hydroxy-3-methylglutaryl coenzyme A reductase, which is the key enzyme for cholesterol synthesis. Mice transgenic for the prokaryotic chloramphenicol acetyl transferase (CAT) reporter gene fused with a 5' Bam H1 fragment including the promoter sequence for murine HMGCR gene have been obtained. Homozygote transgenic mice were derived from a particular line selected for similar regulation of endogenous HMGCR and the transgene expression by nutritional conditions in different tissue. In addition, high expression of the transgene was evidenced in the brain. Cellular expression of the CAT gene in the central nervous system (CNS) was investigated by immunohistochemistry (IHC). This study was performed on frozen sections of the developing and adult brain, using a rabbit anti-CAT antiserum especially raised for that purpose. CAT expression was observed in some rare individuals in different neural cell types including Purkinje cells and astrocytes. But the most outstanding observation was the high level of CAT expression correlated with differentiated pattern of oligodendrocyte (Ol) distribution observed in white-matter tracts. Double and triple labeling for CAT and stage-specific antigens were performed on transgenic Ol-enriched preparations and cultures. This study showed a normal sequence of differentiation in the transgenic oligodendroglial cell lineage and demonstrated a strict correlation between late differentiation and activation of the CAT gene in these cells: CAT expression started in transgenic Ols between galactocerebroside (GC)-positive and myelin basic protein (MBP)-positive stages and was detected in MBP-positive cells during the myelination period. After myelination, the number of CAT-positive Ols decreased in the adult brain. These observations demonstrate a developmental regulation of the CAT transgene in Ols during myelination in CNS and reinforce the hypothesis of endogenous synthesis as major source of cholesterol during myelination.

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PubMed1994

Contribution of transplantations to the understanding of the role of the PLP gene.

We present an overview of the results obtained in a cross-transplantation system using respectively controls, jimpy (jp), and shiverer mutant mice as donors and recipients. Homochronic transplantations (O days into O days) demonstrated that jp environment is non-toxic for non-jp cells and that, contrary to in vitro, jp oligodendrocytes phenotype cannot be modified by environmental factors at this age. Transplantations of embryonic fragments into the newborn brain demonstrated that in contrast to oligodendrocyte precursors contained in fragments of newborn tissue, jimpy embryonic stem cells are sensitive to environmental factors able to modulate the proportion of surviving oligodendrocytes. In addition, these series evidenced a disjunction between the surviving and the myelinating capacity of jp cells demonstrating a pleiotropic effect of the jp mutation on oligodendrocyte biology. Results are discussed with regards to the recent molecular biological finding on the role of the DM20/PLP gene.

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PubMed1992

The fate of Schwann cells transplanted in the brain during development.

Purified rat Schwann cells labeled with Hoechst 33342 fluorescent fluorochrome were transplanted into the brain of the newborn shiverer mouse. The grafted cells survived and were able to migrate through the host parenchyma. However, Schwann cell migration was restricted to the grafted hemisphere and to structures adjacent to the graft. With time, Hoechst labeled cells, present at the site of implantation or dispersed in the host parenchyma, decreased progressively in number. Instead, they concentrated along the blood vessels, meninges and ventricles. Despite the presence of Hoechst labeled Schwann cells in white matter tracks during the process of central myelination, Schwann cell myelination could not be evidenced by immunodetection of the peripheral myelin protein or by ultrastructural observation of the typical Schwann cell basement membrane surrounding peripheral myelin. A series of additional transplantations involving Schwann cells of mouse or rat origin, grafted either as cell suspensions or as nerve fragments, demonstrated that transplanted Schwann cells formed myelin around developing host axons only when included in a nerve fragment. Immunodetection of GFAP in astrocytes and type IV collagen in basement membranes as well as electron microscopy showed that reactive astrocytes invaded the grafted area after the first week of transplantation and sometimes formed basement membranes isolating partially the graft from the host parenchyma. During host myelination, astrocytes, which were present in most white matter structures, surrounded grafted cells. Occasionally, they enclosed Schwann cells in basement membranes or encircled host axons. Later, reactive astrocytes were associated with Schwann cells restricted to blood vessel and ventricular walls, and meninges. Our results suggest that in the presence of competitive developing oligodendrocytes, astrocytes are able to limit migration and prevent myelination of Schwann cells transplanted in the newborn shiverer brain. In addition, astrocytes seem to be able to expel the grafted cells and finally exclude them from the host parenchyma.

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PubMed1992

Oligodendrocytes from jimpy and normal mature tissue can be 'activated' when transplanted in a newborn environment.

Fragments of corpus callosum from P13 normal and jimpy (jp) mutant mice (containing only postmigrating precursors and differentiated oligodendrocytes (ODCs, some of them myelinating soon) have been transplanted into the thalamus of newborn shiverer (shi) mutant mice. The behaviour of transplanted ODCs has been assayed by immunohistochemistry of their myelin basic protein (MBP)-positive myelin synthesized in the host shi brain whose myelin is deprived of this component. ODCs and postmigrating precursors contained in P13 normal corpus callosum survived, migrated out of the graft and myelinated in the shi host parenchyma. The high ratio of positive cases observed was comparable to the one observed in previous experiments using fragments of newborn or embryonic normal tissue. When fragments of jp tissue were used as donors, postmigrating jp ODCs or precursors migrated on long distances out of the graft and synthesized large amounts of myelin as estimated by the size of the MBP-positive myelin patches present in the host shi brain. The extent of migration and the size of these myelin patches were more important than those observed in previous experiments using fragments of newborn or embryonic jp CNS as donors. By contrast, the low ratio of positive cases observed suggested that the survival of P13 jp ODCs or their postmigrating precursors cannot be restored by the newborn shi environment.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1991

Tracing transplanted oligodendrocytes during migration and maturation in the shiverer mouse brain.

Fragments of neural tissue from normal newborn mouse were stained with Hoechst 33342 dye before transplantation into the newborn shiverer mouse brain. Combination of this technique with immunohistochemistry demonstrated that, after transplantation, these cells are able to survive as long as unstained cells and to myelinate in the shiverer mouse host brain. Stained cells express the normal sequence of differentiation in terms of chronology of differentiation marker expression [04, galactocerebroside (GalC), myelin basic protein (MBP)], as normal cell do in situ. It has thus been possible by this technique to show the migration pathways of transplanted cells and to correlate them with the expression of specific markers: long distance migration along white matter axonal pathways occurs when cells are o4-positive, GalC-negative. By contrast, only GalC-positive cells are able to migrate across the grey matter in the absence of radial glia. Finally, it has been possible to propose a migration and differentiation sequence of these cells, suggesting that MBP-positive oligodendrocytes divide after migration in the target zone.

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PubMed1991

Oligodendrocytes of the jimpy phenotype can be partially restored by environmental factors in vivo.

Cross-transplantations of neural tissue between jimpy (jp) shiverer (shi) and normal mice have been performed under heterochronic conditions. In all series, fragments of E14-E15 embryonic neural tissue from the different donors have been transplanted into newborn host brain in order to study environmental influences by differentiated tissue on transplanted embryonic cell lines. Large patches of proteolipid protein (PLP)-positive myelin have been observed in the jp brain after transplantation of shi or normal embryonic tissue into the newborn jp brain, suggesting that the jp parenchyma did not inhibit the differentiation of other oligodendrocytes (ODCs). Jp embryonic tissue had the same mitotic potential as normal tissue, as demonstrated by the larger size of myelin patches observed when jp embryonic tissue was used instead of newborn jp tissue. By contrast, whatever the conditions, jp myelin patches were always obviously smaller than normal or shi myelin patches, suggesting that the myelinating capacity of jp ODCs was not enhanced by environmental factors. Finally, comparison of the ratio of successful outcomes observed following embryonic vs. newborn jp donor tissue, strongly suggests a partial or total normalization of jp embryonic ODCs survival by a more mature shi environment.

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PubMed1990

Patchy myelination pattern in the jimpy mouse brain: immunohistochemical study.

The jimpy (jp) mutation of the mouse leads to a dramatic decrease of myelination in the hemizygous mutant central nervous system (CNS). Several descriptions based on classical histology, immunohistochemistry, and electron microscopy (EM) have demonstrated the scarcity of myelin formation in the different parts of the CNS. The immunohistochemical study presented here showed a very singular patchy pattern of myelin distribution in the different areas of the whole mutant brain. The myelin patches are randomly dispersed without bilateral symmetry, and their density and location vary from one animal to another. No reproducible pattern of myelination could be found among the population observed. This distribution has been compared with observations on young heterozygotes and wild-type homozygotes from the same strain. A similar patchy and random distribution of myelin could be observed in heterozygotes, which present an intermediate level of myelination. This strongly suggests that a migration of precursors or immature oligodendrocytes (ODCs) from the periventricular zone followed by local multiplication of colonies of ODCs before myelination is a general feature in normal as well as pathological conditions.

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PubMed1990

Immunohistochemical studies on cross-transplantations between jimpy, shiverer, and normal newborn mice.

Cross-transplantations of neural tissue have been performed between jimpy (jp), shiverer (shi), and normal mice. Taking advantage of the absence of immunodetectable myelin basic protein (MBP) in the shi brain, jp myelin has been identified in the shi recipient by using an anti-MBP antiserum. By contrast, shi as well as normal myelin have been identified in the jp brain by using an anti-C-terminal hexapeptide of the proteolipid protein (PLP) (this PLP hexapeptide being absent in the jp PLP). When transplanted under homochronic conditions (newborn into newborn), jp oligodendrocytes (ODC) express their usual phenotype in a normal or a shi environment, suggesting that at birth the jp ODCs phenotype is strictly established and cannot be modified by environmental conditions. The reverse transplantations (newborn shi or normal into newborn jp brain) demonstrate that the jp environment does not modify the phenotype of normal or shi ODCs. Finally, these experiments demonstrated a normal timing of differentiation of jp axons and of jp ODCs.

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PubMed1989

Morphometric and freeze-fracture studies on peripheral nerve in shiverer mice.

Observations have been made on the peripheral nerves of shiverer (shi/shi) mice in comparison with control animals. Although this mutant lacks P1 myelin basic protein in peripheral and central myelin, myelin is defective only in the central nervous system. No ultrastructural abnormalities were observed in the shiverer nerves. Myelin spacing was normal. The density and distribution of intramembranous particles on the E and P faces of myelin and in the axolemma of myelinated and unmyelinated axons did not differ between the shiverer and control mice. Morphometric studies showed that external myelinated fiber diameter was significantly less and that myelin thickness was slightly but significantly greater in relation to axon diameter in the shiverer mice, suggesting a minor degree of axonal atrophy. It is concluded that P1 protein is not necessary for the formation and maintenance of the normal structure of peripheral myelin. The failure to detect differences in intramembranous particle density in myelin between shiverer and control mice indicates that P1 protein is not detected in freeze-fracture preparations.

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PubMed1988

Myelination by oligodendrocytes isolated from 4-6-week-old rat central nervous system and transplanted into newborn shiverer brain.

Oligodendrocytes isolated from 4-6-week-old rat brains were transplanted into newborn shiverer brains. Cells were identified as mature oligodendrocytes both by immunocytological and ultrastructural criteria. Normal myelin was detected using immunolocalisation (with an anti-MBP antiserum) and electron microscopy (presence of the major dense line). Patches of normal myelin (made by transplanted oligodendrocytes), widely spread throughout the host brains, were detected between 20 and 130 days after grafting. No sign of acute rejection was observed, but the graft became progressively delimited by astrocytic processes forming a continuous basal lamina.

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PubMed1988

[Comparative expression of 2 intermediate filament proteins, peripherin and the 68 kDa neurofilament protein, during embryonal development of the rat].

Peripherin, an intermediate filament protein, was originally detected by biochemical methods in the neurons of the peripheral nervous system. We now studied its expression and cellular localization by immunocytochemical methods in the developing rat embryo, and compared them with the expression and localization of the 68 kDa neurofilament protein. It appears that peripherin is expressed not only in the neurons of the peripheral nervous system, but also in some well defined neuronal populations of the central nervous system. These results focus on the questions of the phylogenetic origin and of the function of peripherin.

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PubMed1987

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↗
PubMed1987

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↗
PubMed1987

[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.

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PubMed1986

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.

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