Biomedical subjects

Sophie Layé

Publications and source records attributed to Sophie Layé.

6 recordsLinked to original sources

PubMed2006

Characterization of STAT3-expressing cells in the postnatal rat brain.

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor abundantly expressed in the postnatal brain that is involved in the differentiation of cultured astrocytes. Thus far, the cellular identity and anatomical distribution of STAT3-expressing cells in the postnatal brain is poorly known. This study identifies the cell type(s), anatomical location, and temporal distribution of STAT3-expressing cells by using immunohistochemistry and confocal microscopy on postnatal day 3 (P3), 10 (P10), and 21 (P21) rat brain sections. Furthermore, the phosphorylation of STAT3 on tyrosine and serine residues was analyzed at these different stages by immunoprecipitation followed by Western blot. STAT3 immunoreactivity was observed in the cytoplasm and nucleus of many maturating astrocytes positive for nestin (at P3) or positive for GFAP (at P10) distributed throughout the white and grey matter. Moreover, robust nuclear immunoreactivity was observed in brainstem motoneurons. Phosphorylation on tyrosine and serine was observed at P3 and increased at P10, which suggests an augmented activation of STAT3 at the mid-postnatal period. At P21, STAT3 immunoreactivity dramatically decreased to remain visible only in the cytoplasm of white matter astrocytes and hypothalamic and brainstem neuronal groups. Furthermore, while the phosphorylation of tyrosine residues tended to decrease, that of serine residues further increased. In summary, our study reveals a complex regulation of STAT3 phosphorylation in the postnatal brain and provides in vivo evidence of the specific expression of STAT3 in maturating astrocytes and brainstem motoneurons.

Animals↗

PubMed2003

Specific localization of signal transducer and activator of transcription 1 immunoreactivity in oxytocin neurons of the rat hypothalamus.

The transcription factor STAT1 participates in signaling pathways and cellular responses triggered by several cytokines, growth factors and hormones. The present work demonstrates for the first time the immunohistochemical distribution of STAT1 in the rat hypothalamus. STAT1 immunoreactivity was observed in somas, dendrites and axons of neurons throughout the supraoptic and paraventricular nuclei and co-localized specifically with oxytocin. These findings indicate that STAT1 is positioned to participate in specific neuroendocrine regulation in the nonpathological rat brain.

Animals↗

PubMed2003

Nuclear factor kappaB nuclear translocation as a crucial marker of brain response to interleukin-1. A study in rat and interleukin-1 type I deficient mouse.

The signalling pathways that mediate early central effects of interleukin-1 (IL-1) during the acute phase reaction have been poorly elucidated. Interaction of IL-1beta to its specific receptor interleukin-1 receptor type I (IL-1RI) leads to nuclear factor kappa B (NuFkappaB) nuclear translocation and a robust transcriptional activation of inhibitor of kappa B alpha (IkappaBalpha) within the rat brain. Indeed, we demonstrated that IL-1RI expressed in blood brain barrier (BBB) cells and in circumventricular organs (CVOs) is crucial for p65-NFkappaB translocation induced by peripheral injection of IL-1beta. Moreover, it has been previously shown that monitoring IkappaBalpha mRNA synthesis is an effective tool to investigate the activity of the transcription factor NFkappaB into the CNS. However in the present study we observed time-related and cell-type differences between IkappaBalpha mRNA synthesis and p65-NFkappaB translocation. This indicates that the expression of IkappaBalpha mRNA does not strictly parallel p65-NFkappaB nuclear translocation, suggesting that these markers are not interchangeable to investigate NFkappaB activity but must be studied together. Thus, we hypothesize that IL-1beta reached the brain across the CVOs that lack a BBB and endothelial cells all over the brain and interacted with its receptors to induce NFkappaB translocation. The study of the consequences of the impairment of NFkappaB pathway activation in in vivo experimentation should bring important clues about the precise role of this transcription factor.

Active Transport, Cell Nucleus↗

PubMed2003

In vivo activation of the interleukin-6 receptor/gp130 signaling pathway in pituitary corticotropes of lipopolysaccharide-treated rats.

Adrenocorticotropic hormone (ACTH) release from anterior pituitary corticotropes is greatly increased during peripheral inflammation induced by lipopolysaccharide (LPS) administration. Interleukin-6 (IL-6) is thought to participate in LPS-induced ACTH release, but whether or not corticotropes are directly targeted by this cytokine is unclear. Therefore, we investigated the expression and activation of IL-6 signaling components in the pituitary of rats 2 and 4 h after administration of LPS (250 microg/kg). Intraperitoneal LPS treatment provoked the nuclear translocation of signal transducer and activator of transcription 3 (STAT-3) and Fos expression in the anterior pituitary lobe, as demonstrated by immunohistochemistry. By using in situ hybridization, we demonstrated that suppressor of cytokine signaling 3 (SOCS-3) and c-fos mRNAs were significantly induced by the LPS treatment in the anterior lobe of the pituitary. Dual in situ hybridization revealed that most corticotropes expressed IL-6 receptor and gp130 mRNAs, and that 2 h after LPS treatment, SOCS-3 and c-fos mRNAs were induced in corticotropes. Our results suggest that LPS-induced IL-6 could regulate the hypothalamo-pituitary-adrenal axis by directly targeting corticotropes during peripheral inflammation.

Animals↗

PubMed2003

[Cytokines and nutritional disorders].

During an infection, a decrease in food intake together with elevated energy expenditure appears. Anorexia is one of the most common signs of illness and is often considered as an undesirable manifestation of sickness. However, compelling data demonstrate that anorexia constitutes an adaptative strategy systematically organised for pathogens elimination. Microbial products stimulate the production by immunocompetent cells of cytokines, which orchestrate the immune response. Since the administration of cytokines reduces food intake, it has been suggested that these agents play a key role in mediating anorexia during infection. This review details the mechanisms of cytokine-induced anorexia, focusing on the role of endogenously produced brain cytokines and more particularly interleukin-1 (IL-1). De novo synthesis of IL-1 occurs in the brain during peripheral infection mimicked by the administration of bacterial endotoxin lipopolysaccharide (LPS). Centrally produced IL-1 acts on its receptors to mediate anorexia as demonstrated by the use of knockout mice and specific IL-1 receptor antagonist. Functional neuroanatomy demonstrates further that LPS or IL-1 specifically activates the hypothalamic neurons that control food intake. Leptin is tightly regulated by IL-1, suggesting the involvement of this hormone in the anorexia of infection. The mechanisms by which hypothalamic arcuate nucleus neuropeptides, which are regulated by IL-1 and leptin, could mediate anorexia during infection are discussed.

Animals↗

PubMed1998

Molecular basis of sickness behavior.

Peripheral and central injections of lipopolysaccharide (LPS), a cytokine inducer, and recombinant proinflammatory cytokines such as interleukin-1 beta (IL-1 beta) induce sickness behavior in the form of reduced food intake and decreased social activities. Mechanisms of the behavioral effects of cytokines have been the subject of much investigation during the last 3 years. At the behavioral level, the profound depressing effects of cytokines on behavior are the expression of a highly organized motivational state. At the molecular level, sickness behavior is mediated by an inducible brain cytokine compartment that is activated by peripheral cytokines via neural afferent pathways. Centrally produced cytokines act on brain cytokine receptors that are similar to those characterized on peripheral immune and nonimmune cells, as demonstrated by pharmacologic experiments using cytokine receptor antagonists, neutralizing antibodies to specific subtypes of cytokine receptors, and gene targeting techniques. Evidence exists that different components of sickness behavior are mediated by different cytokines and that the relative importance of these cytokines is not the same in the peripheral and central cytokine compartments.

Animals↗