PubMed Health⌕ Search

Biomedical subjects

C Fages

Publications and source records attributed to C Fages.

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

Thyroid hormones influence the astroglial plasticity: changes in the expression of glial fibrillary acidic protein (GFAP) and of its encoding message.

Normal development of the brain requires the presence of thyroid hormones. To progress in the understanding of the contribution of astrocytes to brain pathophysiology we investigated the effect of T3, on the astroglial plasticity through the expression of two astroglial proteins: the Glial fibrillary acidic protein (GFAP) and the glutamine synthetase (GS). Western and northern blots were performed using astroglial primary cultures initiated from neocortex and cerebellum of new-born mice. Treatment with T3 caused a decrease of GFAP and of its encoding message level in both areas, suggesting a transcriptional regulation of its expression, whereas it had no apparent effect on GS expression. This reduction in GFAP expression was developmentally regulated; it was significant in proliferating but not in more mature astrocytes. T3 effect on astrocytes was higher in the cerebellum compared to the neocortex, suggesting the presence of astroglial subpopulations differing by their sensitivity to T3. The astroglial specific response to T3, corresponds to a precise, targetted and regulated adaptation of the cell. Factors of the microenvironment may modulate this specific astroglial response in vivo.

Animals↗
PubMed1994

Expression of glial fibrillary acidic protein and glutamine synthetase genes in the natural scrapie of sheep.

Gene expression of two astroglial markers, glial fibrillary acidic protein (GFAP) and glutamine synthetase (GS), was investigated in cerebellum and brainstem from scrapie-affected sheep. The GFAP and GFAP-mRNA concentrations were increased in the two cerebral regions studied in the scrapie-affected animals as compared to the controls. The good correlation between the increase in GFAP and GFAP-mRNA concentrations found in scrapie-affected sheep indicates a significant de novo synthesis of GFAP in this pathology. In contrast to these results, in scrapie no significant differences in GS-mRNA content appeared in either brain area from scrapie-affected sheep as compared to the controls. This fact could suggest some specificity of GFAP expression changes in this pathology. The overexpression of GFAP gene could be related to a possible interaction between GFAP and scrapie infectious agent in astrocytes. The relative increase in the GFAP and its encoding message in affected animals was higher in the cerebellum than in the brainstem, which would suggest regional comparative differences in the effect here described.

Animals↗
PubMed1994

Glutamine synthetase modulation in the brain of rats subjected to deprivation of paradoxical sleep.

Changes in the level of glutamine synthetase (GS), an enzyme mainly located in astrocytes, were investigated in rat brain after deprivation of paradoxical sleep (PSD) and during recovery. An immunotitration method was used to evaluate the relative level of GS in brain tissue. At the end of a 24 h PSD, a significant increase in GS protein was observed both in the frontoparietal cortex (CX) and in the locus coeruleus area (LC). Four hours later during recovery, the level of GS protein returned to normal level in the CX but fell below control levels in the LC. In contrast, in the CX, the level of glial fibrillary acidic protein, an astroglial marker, did not change after PSD or during recovery. GS mRNA was quantified in the entire cortex by northern blot hybridization using of an oligonucleotidic GS-cDNA probe. We observed an increase in the GS mRNA level in the cortex of PSD rats of the same magnitude as the increase in GS protein. Both GS mRNA and GS protein tended to return to control values 4 h later during recovery. These results are discussed with particular attention to stress effects and possible physiological mechanisms regarding the regulation of amino acid levels by neurotransmitters during prolonged waking or neuronal excitation.

Animals↗
PubMed1994

Effects of modafinil-induced wakefulness on glutamine synthetase regulation in the rat brain.

Changes in the level of glutamine synthetase (GS), an enzyme chiefly found in glial cells, were investigated in the brains of rats treated with modafinil, an awakening drug interfering with central catecholamine function. Two hours (waking period) and 7 h (recovery period) after intra-peritoneal injection of 128 mg/kg modafinil, a significant increase in the level of GS protein was observed by immunotitration in both the locus coeruleus (+30%) and in the frontoparietal cortex (+50%). No changes were observed with 64 mg/kg of modafinil. GS mRNA was quantified in the entire cortex by Northern blot hybridization using an oligonucleotidic GS cDNA probe. A significant increase in the GS-mRNA level (+70%) was observed in the CX of rats 2 h after injection of 128 mg/kg modafinil; the level tended to return to control values 7 h later during the recovery period. The level of glial acid fibrillary protein (GFAP), an astroglial marker, was unchanged after modafinil treatment. These changes in GS levels after modafinil treatment are discussed in terms of neuron-glia interactions in the regulation of brain metabolism during pharmacologically induced wakefulness, excluding possible stress effects.

Animals↗
PubMed1993

Alterations of glial fibrillary acidic protein mRNA level in the aging brain and in senile dementia of the Alzheimer type.

The GFAP mRNA levels were compared to the density of the senile plaques (SP) in postmortem brain samples of 8 cases, either non-demented or affected by senile dementia of the Alzheimer type. In the frontal neocortex, the GFAP mRNA level is not affected, even if SP are present. In the temporal neocortex, a positive correlation between GFAP mRNA level and SP density was highly significant. This shows that in this area, astrocytes are altered at transcriptional or post-transcriptional levels, or both. The different responses of this astrogliosis marker in each area may be related to the loss of specific neurotransmitter system.

Aged↗
PubMed1993

Glial fibrillary acidic protein and its encoding mRNA exhibit mosaic expression in a glioblastoma multiform cell line of clonal origin.

The expression of two astroglial differentiation markers, vimentin and glial fibrillary acidic protein, was investigated in a previously established human glioma cell line of clonal origin (GL15). Vimentin immunolabelling was homogeneously expressed in all cells. Glial fibrillary acidic protein and its encoding message, investigated by immunocytochemistry and in situ hybridization, showed a mosaic-like expression. Only 30% of the cell population expressed glial fibrillary acidic protein and its mRNA. Western and Northern blots performed for both markers confirmed the presence of both proteins and messages, and their level was correlated with the observed antigenic and molecular probe labelling. The overall antigenic pattern suggests that GL-15 cells do not belong to the O-2A progenitor cell lineage and may arise from a clonal expansion of astrocyte precursors.

Biomarkers↗
PubMed1992

Transcriptional regulation of glial fibrillary acidic protein (GFAP)-mRNA expression during postnatal development of mouse brain.

During mouse brain maturation, GFAP-mRNA undergoes a two-step developmental expression. It increases between birth and day 15 (period of astrocytic proliferation) and then decreases until day 55 (period of astrocytic morphological differentiation). We have developed an in vitro transcription procedure, as a mean to study the part of transcriptional control in this biphasic expression. After RNA synthesis by endogenous RNA polymerases in nuclei isolated from mouse brain (of 3 to 55 days and 217 days), the relative rates of GFAP-mRNA transcripts were analysed by hybridization with a specific cDNA probe. As early as 3 days after birth, the rate of GFAP-mRNA transcripts was maximal, whereas unexpectedly, it showed a significant decrease in mice of 15 days and stayed low until the 55th day. Therefore, a transcriptional control may take place early in mouse brain postnatal development by increasing the transcriptional rate of the GFAP gene in astrocytes, and during the transition from proliferation to differentiation phase of astrocytes (that occurs at the 15th day after birth) by decreasing this rate. However, posttranscriptional events may also occur to modulate the level of the cytoplasmic GFAP-mRNA. In older mice (217 days), the low rate of GFAP-mRNA transcripts found is not concordant with the high cytoplasmic level generally observed in gliosis of the aging brain. Our data suggest posttranscriptional events at this age.

Aging↗
PubMed1991

Effect of thyroid deficiency on glial fibrillary acidic protein (GFAP) and GFAP-mRNA in the cerebellum and hippocampal formation of the developing rat.

The concentrations of glial fibrillary acidic protein (GFAP) and its encoding mRNA in the cerebellum and hippocampal formation were assayed during the development of normal and hypothyroid rats. Neonatal hypothyroidism induced a significant reduction in the GFAP concentration in both regions from day 14. The reduction was especially marked on day 35 in the cerebellum (-43%) and the hippocampal formation (-55%). The immunocytochemical study of vimentin showed that the developmental disappearance of this protein from the Bergmann and internal astrocytes is greatly delayed in the cerebellum of the hypothyroid rats. The reduction in GFAP concentration together with the delayed vimentin-GFAP transition could explain how astrocyte morphogenesis is impaired by neonatal thyroid deficiency. The GFAP-mRNA concentration in the hippocampal formation was reduced throughout the development of thyroid-deficient rats, while the GFAP-mRNA concentration in the cerebellum first increased between birth and day 14 to reach a peak well above the normal value (+78%) and decreased thereafter to reach 53% of the normal value by day 35. This transient increase in the cerebellar GFAP-mRNA concentration may be related to the astroglial hyperplasia that occurs in these animals. The difference between the developmental profile of GFAP and its encoding mRNA, especially under pathological conditions, indicates that two distinct mechanisms control the synthesis or stability of the protein and its messenger RNA, as was previously found in the forebrain of the developing normal rat.

Animals↗
PubMed1991

DBcAMP effect on the expression of GFAP and of its encoding mRNA in astroglial primary cultures.

Short term and chronic dBcAMP effects on the expression of glial fibrillary acidic protein (GFAP) in astroglial primary cultures are investigated. Short (48 h) and long (more than 7 days) treatments with the cAMP derivative induce both cell shape changes and an increase in GFAP immunolabelling. Such effects are only associated with an increase in GFAP and in GFAP-mRNA levels in the long term treatment. These results suggest that the short term effect of dBcAMP induces post-translational modifications of the protein whereas the long term effect is associated with an increase in GFAP mRNA transcription and/or stability.

Animals↗
PubMed1990

GFAP turnover during astroglial proliferation and differentiation.

The expression and turnover of the glial fibrillary acidic protein (GFAP) were studied in astroglial primary cultures during postnatal proliferation and maturation. 1. Immunocytochemical studies demonstrated that in immature proliferating astrocytes. GFAP was expressed as a filamentous organized crown around the nucleus whereas in the maturating cells, a GFAP labelled network began to radiate throughout the cytoplasm and GFAP was highly expressed in the astroglial processes. 2. GFAP turnover was studied at 3 periods of culture. The decay of radioactivity from prelabelled GFAP was followed from day 4-12 (immature stage), 11-19 (maturing stage) and 21-29 (morphologically differentiated stage). GFAP displayed a biphasic decay kinetic at each considered period. Two pools of GFAP distinctly appeared. The first one was a fast decaying pool with a half life of 16-18 h and of 5-6 days for the stable one. The unstable pool decreased from 70% to 30% of the total incorporated radioactivity from the proliferating stage to the most mature stage, whereas the stable pool increased proportionally.

Animals↗
PubMed1990

Glutamine synthetase modulation in astrocyte cultures of different mouse brain areas.

Astroglial cells from mouse cerebral hemispheres, cerebellum, olfactory bulbs, and medulla oblongata were grown in the presence of either hormones (hydrocortisone, insulin) or cell second messengers (dBcAMP, dBcGMP). Glutamine synthetase (GS) specific activity, GS protein level, and GS translation were investigated under the effect of these factors. Hydrocortisone produced a simultaneous increase in GS translation, GS level, and activity. This increase was observed in the astrocytes cultured from the four brain areas but at a variable magnitude depending on the area. The hydrocortisone effect appeared at the transcriptional level. Inversely, insulin decreased both the GS activity and the in vitro translated GS. This effect was seen only in the olfactory bulbs and the medulla. DBcAMP increased the GS biological activity only in the cerebral hemisphere cultures. It raised, however, the level of translated GS and GS protein in astrocytes from all the areas, suggesting a post-translational effect for intracellular cAMP. DBcGMP only affected GS in the astrocytes from cerebral hemispheres and the medulla modulating either the GS transcription or the messenger RNA stability. These results suggest specific regulation for GS expression, depending on the brain area from which the cells were dissociated or on the astroglial cell population present in these cultures affecting either the transcription, the mRNA stability, or the biological activity of the protein.

Animals↗
PubMed1989

Developmental expression of the glial fibrillary acidic protein mRNA in the central nervous system and in cultured astrocytes.

The expression of glial fibrillary acidic protein (GFAP)-mRNA during mouse brain development and in astroglial primary cultures has been investigated by using two approaches: Northern-blot evaluation using a specific cDNA probe, and cell-free translation associated with immunoprecipitation. During brain maturation (4-56 days postnatal), the GFAP-mRNA underwent a biphasic evolution. An increase was observed between birth and day 15 (i.e., during the period of astroglial proliferation), which was followed by a decrease until day 56 (i.e., during astroglial cell differentiation). At older stages (300 days), an increase was observed, which might reflect gliosis. During astroglial in vitro development (7-32 days in culture), the GFAP-mRNA showed similar variations. An increase, observed during the period of astroglial proliferation (7-18 days), was followed by a decrease which occurred in parallel to marked changes in cell shape, cell process outgrowth, and the organization and accumulation of gliofilaments. During the same culture period (7-32 days), alpha-tubulin mRNA, which was used as an internal standard, did not vary significantly. These results show that the increase of the GFAP protein and of gliofilaments observed both in vivo and in vitro during astroglial differentiation cannot be ascribed to an accumulation of the GFAP-mRNA. It might be that more than one mechanism regulates the levels of free and polymerized GFAP and of its encoding mRNA.

Animals↗
PubMed1988

Insulin effect on GABA uptake in astroglial primary cultures.

Astroglial cultures from newborn mouse cerebral cortex contain [125I]Insulin binding sites. Binding was specific, reversible, time dependent and reached equilibrium after 45 min. Insulin analogues compete for this [125I]Insulin binding. Incubation of cerebral cortex astroglial cultures with insulin induced a time- and dose-dependent inhibition of the [3H]GABA high affinity uptake. A decrease in the Vmax rather than an effect on the Km was observed. This effect was dose-dependent and effective at 10(-10) M. Autoradiographic observations on the cell monolayer showed the presence of two groups of cells: one which strongly takes up [3H]GABA and consist in smaller GFAP positive process-bearing cells and another group of much flatter and larger GFAP positive cells which uptake was lower. The smaller stellate cells were apparently the most sensitive to insulin effect. These results: 1) confirm the presence of insulin binding sites on astroglial primary cultures, 2) show an effect of insulin on [3H]GABA high affinity uptake of these cells; this effect being optimal on a stellate-like population of astrocytes, and 3) indicate that insulin may interfere in neuromodulation through astroglial signals.

Animals↗
PubMed1988

Glutamine synthetase: a marker of an astroglial subpopulation in primary cultures of defined brain areas.

Primary cultures from various areas of newborn mouse brain were developed and characterized. Enriched astroglial cultures of the cerebral hemispheres, cerebellum, medulla oblongata and olfactory bulbs contained about 80-90% glial fibrillary acidic protein (GFA) immunolabelled cells. These cultures were composed of a majority of flat, 'protoplasmic-like' cells. The aim of this culture model was used: (1) to study glutamine synthetase (GS) activity during in vitro astroglial development; (2) to consider the hydrocortisone effect on GS activity during both growth and maturation periods, and (3) to determine the development of GS immunoreactivity in the cells and eventual GFA and GS expression in these cells. We observed that GS increased during brain maturation in vivo and in vitro, and that addition of hydrocortisone (1 microM, 48 h) to the culture medium induced varying GS activity depending on the developmental stage and the area. In the four areas studied, the number and intensity of GS-immunolabelled cells reached an optimum between 18 and 30 days in vitro. Only about 50-70% of the cell population was GS positive. Double-labelling experiments showed that three groups of cells coexist whatever the considered area. Two expressed both GFA and GS proteins, the last marker at either a low or a high level, and the third was devoid of GS immunoreactivity. Regional differences in GS-specific activity, GS inducibility and GS immunoreactivity exist in the astroglial population, but the factors responsible for these variations are not yet known.

Animals↗
PubMed1986

Differential immunocytochemical staining for glial fibrillary acidic (GFA) protein, S-100 protein and glutamine synthetase in the rat subcommissural organ, nonspecialized ventricular ependyma and adjacent neuropil.

Antibodies raised against glial fibrillary acidic protein (GFA), S-100 protein (S100) and glutamine synthetase (GS) are currently used as glial markers. The distribution of GFA, S100 and GS in the ependyma of the rat subcommissural organ (SCO), as well as in the adjacent nonspecialized ventricular ependyma and neuropil of the periaqueductal grey matter, was studied by use of the immunocytochemical peroxidase-antiperoxidase technique. In the neuropil, GFA, S100 and GS were found in glial elements, i.e., in fibrous (GFA, S100) and protoplasmic astrocytes (S100, GS). The presence of S100 in the majority of the ventricular ependymal cells and tanycytes, and the presence of GFA in a limited number of ventricular ependymal cells and tanycytes confirm the glial nature of these cells. The absence of S100, GFA and GS from the ependymocytes of the SCO, which are considered to be modified ependymal cells, suggests either a non-astrocytic lineage of these cells or an extreme specialization of the SCO-cells as glycoprotein-synthesizing and secreting elements, a process that may have led to the disappearance of the glial markers.

Animals↗
PubMed1986

Absence of correlations between glutamine-synthetase activity and dysmyelination-associated modifications of astroglia in the brain of murine mutants.

Glutamine Synthetase (GS) activity was investigated in cerebellum (ce), cerebral cortex (cc), olfactory bulb (ob), and medulla oblongata (mo) of murine dysmyelinating mutants for correlations with modifications of astroglia associated with genetic dysmyelination. One of these mutants, jimpy, develops a strong gliosis throughout the CNS. The other three mutants: shiverer, mld, and quaking, exhibit various astrocytic responses to dysmyelination, but reduced gliosis if any. Comparison between CNS areas in control animals showed a higher GS activity in the olfactory bulb than in the cerebral cortex, medulla, and cerebellum. The developmental patterns of GS activity were similar in mutants and in controls in all four areas investigated. Data on Jimpy suggest that GS activity is not associated with reactive astrocytes.

Animals↗