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Biomedical subjects

B Chamak

Publications and source records attributed to B Chamak.

At least 19 recordsLinked to original sources

The emergence of cognitive science in France.

A comparison between the development of cognitive science in France and the USA enables us to analyze some national differences linked to specific connections between the scientific, military, economic and political worlds. The influence of new practices and tools developed during World War II and the Cold War appears to be of crucial importance in understanding the development of this new field, as well as that of cybernetics, computer science, artificial intelligence and molecular biology. This paper can be considered as a study in how the differing contexts in France and the USA shaped the history of the construction of cognitive science in each of these two countries. In spite of various differences, some common aspects may be pointed out: in both cases, computer experts and psychologists using a computational modelling approach were those first engaged in the construction of cognitive science. If in France neuroscience-oriented cognitive science research was stronger than in the USA, it seems that the artificial intelligence orientation is also of growing importance in France.

Artificial Intelligence↗

Biopersistence of cerium in the human respiratory tract and ultrastructural findings.

For diagnostic purposes, mineralogical analysis was performed in bronchoalveolar lavage fluid and lung tissue from a 58-year-old patient previously exposed to asbestos and rare earth dusts. No significant retention of asbestos was demonstrated in lung tissue by light microscopy (asbestos bodies) or transmission electron microscopy analysis (uncoated fibers). Particles containing rare earth (cerium, lanthanum) and phosphorus were identified in alveolar macrophages in bronchoalveolar lavage fluid, and cerium-containing particles accounted for 70% of particles observed in the lung tissue. Ultrastructural analysis of lung tissue revealed the presence of particles containing cerium and phosphorus in interstitial macrophages and elastic fibers. These results suggest that rare earth is metabolized and should be considered as biopersistent in the human respiratory tract, since occupational inquiries revealed that exposure to cerium oxide abrasive powder had ceased at least 15 years earlier.

Asbestos↗

Immunohistochemical detection of thrombospondin in microglia in the developing rat brain.

The development of microglia involves the expression of a phenotype displaying phagocytic behaviour termed brain macrophage or amoeboid microglial cell. We have previously shown that rat brain macrophages purified in vitro secrete thrombospondin, an extracellular matrix protein, which acts on cultured neuronal cells by promoting neurite growth. In the present study, the expression of thrombospondin was investigated in tissue sections of the developing rat forebrain in relation to the distribution of microglia. These cells were identified using anti-macrophage antibodies and the isolectin B4 from Bandeiraea simplicifolia. Immunocytochemical detection of thrombospondin clearly outlined a cell population displaying the morphologies and distribution of brain macrophages, from the 17th day of embryonic life up to the end of the second postnatal week. These cells were most numerous in cortical and subcortical regions of developing fibre tracts such as the corpus callosum or the internal capsule. The localization of thrombospondin in brain macrophages was confirmed by double immunostaining using ED1 monoclonal anti-macrophage antibodies. Ramified microglial cells were also labelled transiently by anti-thrombospondin antibodies during early postnatal life. These results provide in situ evidence supporting the notion that microglial cells could favour axonal growth by producing thrombospondin during development.

Aging↗

Brain macrophages stimulate neurite growth and regeneration by secreting thrombospondin.

The presence of macrophages in the developing or lesioned central nervous system (CNS) led us to study the influence of these cells on neuronal growth. Macrophages were isolated from embryonic rat brain and we observed that factors released in vitro by these cells stimulate neurite growth and regeneration of cultured CNS neurons. This effect was inhibited by antibodies directed against thrombospondin, an extracellular matrix protein that we found to be synthesized and released by brain macrophages. Immunodetection of thrombospondin in the adult rat brain lesioned by kainic acid confirmed the production of this protein by brain macrophages and indicated an early intraparenchymal accumulation of thrombospondin following injury. These results suggest that brain macrophages contribute actively to neurite growth or regeneration during the development or in pathological contexts.

Animals↗

Brain macrophages: neurotoxic or neurotrophic effector cells?

The development of the central nervous system and various pathological contexts imply remodeling or alteration of neuronal networks associated with tissue recruitment of mononuclear phagocytes. Purification and culture of brain macrophages have provided a tool for investigating the functions of these cells. We discuss different mechanisms whereby macrophages could directly influence the survival of neurons and the growth of their processes.

Brain↗

Protein phosphotyrosine in mouse brain: developmental changes and regulation by epidermal growth factor, type I insulin-like growth factor, and insulin.

Using antiphosphotyrosine antibodies, we have investigated protein phosphorylation in mouse brain during development in intact animals and in reaggregated cerebral cultures. Under basal conditions, in vivo and in vitro, the levels of two main phosphoproteins, of Mr 120,000 and 180,000 (pp180), increased with development, reaching a maximum in the early postnatal period and decreasing thereafter. In adult forebrain, pp180 was still highly phosphorylated, but it was not detected in cerebellum or in peripheral tissues. In reaggregated cortical cultures, epidermal growth factor (EGF), type I insulin-like growth factor (IGF-I), and insulin enhanced protein tyrosine phosphorylation of several proteins, which were specific for EGF or IGF-I/insulin. In highly enriched neuronal or astrocytic monolayer cultures, some proteins phosphorylated in basal conditions, or in response to EGF and IGF-I, were found in both types of culture, whereas others appeared cell type specific. In addition, in each cell type, some proteins were phosphorylated under the action of both growth factors. These results indicate that tyrosine protein phosphorylation is maximal in mouse brain during development and is regulated by growth factors in neurons as well as in astrocytes.

Animals↗

Fibronectin and laminin regulate the in vitro differentiation of microglial cells.

During development, the differentiation of ameboid microglia (brain macrophages) into ramified microglia is marked by a loss of macrophage-like properties and the extension of thin cytoplasmic projections. We have studied the influence of two extracellular matrix proteins, laminin and fibronectin, on microglia differentiation, using cell cultures. Brain macrophages were isolated from primary glial layers derived from embryonic rat brain and further cultured in serum-free medium. The addition of fibronectin induced the transformation of round or spindle-shaped brain macrophages into cells displaying a reduced cell body and extending thin and long processes. This morphological transformation was associated with a reorganization of the vimentin network, including a condensation of dispersed filaments into thick bundles and a modification of the phosphorylation state of vimentin monomers. In addition, compared to brain macrophages, the process-bearing microglia lost the ability to engulf zymosan particles, and showed reduction in non-specific esterase activity and superoxide anion generation. In contrast, laminin reduced the spontaneous transformation of brain macrophages into process-bearing cells. Moreover, laminin and serum induced a reverse transformation of process-bearing cells when added to cultures pretreated with fibronectin. Altogether these results demonstrate antagonist effects of fibronectin and laminin on the in vitro differentiation of brain macrophages towards a "resting" phenotype, which shares several properties with the ramified microglia present in the adult brain. We suggest that fibronectin and laminin regulate the differentiation of microglial cells, which takes place during development or following various types of lesions in the adult brain.

Animals↗

Lineage relationship between oligodendrocytes and brain macrophages?

Cells which adhere rapidly in vitro were purified from embryonic rat brain and characterized as macrophages. These characterizations rely on (1) phagocytic behaviour, (2) non-specific esterase activity, (3) immunocytochemical criteria such as the detection of CD4, Mac 1 and class II products of the major histocompatibility complex (MHC II). Morphological transformations observed in the cultures and labeling with anti-galactocerebroside (GalC) antibodies suggest a possible transition between brain-macrophagic and oligodendrocytic phenotypes.

Animals↗

Influence of extracellular matrix proteins on the expression of neuronal polarity.

The influence of laminin (LN) and fibronectin (FN) on the differentiation of individual neurones from the embryonic rat central nervous system was studied in vitro. In control cultures or in the presence of soluble FN, most neurones had several dendrite-like and one axon-like processes. On substratum-bound LN, multipolar and unipolar cells were present. Soluble LN and bound FN induced a very simple neuronal morphology, most neurones having only one axon-like neurite as defined by morphological and immunocytochemical characteristics. The significant reduction of neuronal adhesion and spreading in conditions leading to the growth inhibition of dendrite-like processes suggests that, contrary to that of axons, dendrite growth strongly depends on neuronal adhesion. We propose a model in which the different dependency of axonal and dendritic outgrowth towards adhesion and spreading is explained by the respective physical properties of the two types of neurites.

Animals↗

[Axons, dendrites and adhesion].

The morphology of rat embryonic day 14 (E14) mesencephalic neurons has been studied in vitro under different conditions of neuron-substratum adhesion. Results suggest that decreasing adhesion favors axonal elongation and inhibits the growth of dendrites. This observation is interpreted according to a hypothetical model based on the existence of different physical properties between the two categories of neurites.

Animals↗

Brain astrocytes express region-specific surface glycoproteins in culture.

Astrocytes derived from the mouse brain mesencephalon and striatum regulate neuronal morphogenesis in a region-specific manner in vitro. To begin defining molecular mechanisms that may underlie this functional heterogeneity, lectin probes were used to compare surface glycoproteins expressed by astrocytes from different brain regions. These experiments demonstrated marked differences in surface glycoproteins depending on the anatomic origin of the astrocytes. In particular, mesencephalic and cerebellar astrocytes express a fucosylated glycoprotein with an apparent molecular weight of 190 kD that is absent or rarely expressed by striatal or cortical astrocytes. These findings raise the possibility that carbohydrate diversity of astrocyte surface molecules may play a role in the heterogeneity of region-specific neuron-glial interactions.

Animals↗

Region-specific neuro-astroglial interactions: ultrastructural study of the in vitro expression of neuronal polarity.

Mesencephalic neurons were cultured for 2 days on mesencephalic or striatal astrocyte monolayers. The morphology of these neurons was studied in electron microscopy. The number of dendritic profiles was higher on mesencephalic astrocytes (homotopic neuro-astroglial co-cultures) than on striatal astrocytes (heterotopic co-cultures). This increase in the number of dendrites correlated with a more mature aspect of the neurons. Striatal neurons were also cultured on the astrocytic monolayers. The state of maturation of these neurons was more advanced, and the number of their dendrites was higher on striatal than on mesencephalic astrocytes. These results confirm and extend the fact that neuronal maturation and dendritic growth can be regulated through region-specific neuro-astroglial interactions (Denis-Donini et al., 1984; Chamak et al., 1987).

Animals↗

Rat mesencephalic neurons in culture exhibit different morphological traits in the presence of media conditioned on mesencephalic or striatal astroglia.

Embryonic rat mesencephalic neurons were plated at low density in a chemically defined medium (CDM) or in CDM conditioned on either mesencephalic or striatal astrocytes (CM Gmes and CM Gstr). It was found that "axon-like" neurites, in general long with few branching points, could be initiated in CM Gmes and CM Gstr, whereas "dendrite-like" neurites (shorter and with a high branching capacity) were preferentially initiated in CM Gmes. The effects of CM Gmes and CM Gstr on the morphology of mesencephalic neurons were abolished by protein denaturating treatments. Comparisons with basic FGF, laminin, or fibronectin demonstrated that these three molecules were also able to modify the morphological traits of the neurons. However the different morphologies observed in CM Gmes and CM Gstr could not be explained only by the presence of these proteins in the conditioned media. Our results therefore indicate that different factors may regulate the initiation of different categories of neurites and that in contrast to several molecules able to promote neurite elongation these "initiation" factors may show important regional specificity.

Animals↗

MAP2 expression and neuritic outgrowth and branching are coregulated through region-specific neuro-astroglial interactions.

Embryonic neurons from the rat striatum and mesencephalon were plated on mesencephalic or striatal astrocytes in 4 possible combinations. It was found that specific traits are expressed by the neurons when they are grown on homotopic astrocytes (neurons and astrocytes from the same region). These traits are the following: 1. The number of cells stained with an antibody raised against the microtubule-associated protein 2 (MAP2) is higher in homotopic than in heterotopic cocultures. This is true for both mesencephalic and striatal neurons. 2. In homotopic conditions, there is an increase in the number of cells having more primary neurites and branching points. This effect is observed for both neuronal populations but is more pronounced in mesencephalic neurons. 3. The intensity of MAP2 staining was correlated with the branching ability of the neurons. First, on comparing MAP2-positive and MAP2-negative cells, it was found that, in any combination (homotopic and heterotopic cocultures), the number of primary neurites and branching points was much higher in MAP2-positive cells. In fact, almost no branching activity was found in MAP2-negative neurons. Second, within the MAP2-positive neuronal population, the higher number of branching points observed under homotopic neuro-astroglial conditions was mostly due to the neuritic compartment, which was strongly and homogeneously stained with the anti-MAP2 antibody. These observations strongly suggest that the astrocytic environment regulates the synthesis and/or intracellular distribution of MAP2, as well as the morphology of the neurons, and that this regulation is region specific.

Animals↗

Further studies on the role of astroglia in brain neurons maturation and morphogenesis.

Using in vitro cultures of dissociated brain neurons and astrocytes, we have compared the morphologies of mesencephalic and striatal neurons cultured for two days on mesencephalic and striatal astrocytes in the four possible combinations. From these comparisons, it appears that: 1. Neurons grown on co-regionalized (homotopic) astrocytes have more primary neurites and branching points than neurons grown on heterotopic astrocytes. 2. The total neuritic length is only slightly affected by the type of co-culture. 3. The branched arborization which develop faster on homotopic astrocytes present several dendritic features. Following these morphological observations, we have been able to demonstrate: 1. That mesencephalic astrocytes (but not striatal astrocytes) secrete trypsin sensitive factors different from laminin and FGF that increase the number of primary neurites and branching points but have no or little effect on total neuritic length. 2. That mesencephalic astrocytes (but not striatal astrocytes) present at their surface a 190 KD glycoprotein specifically recognized by the fucose-specific lectin UEA.

Animals↗