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3. Sonic Hedgehog Is an Early Oligodendrocyte Marker During Remyelination.

Author

Russo, Mariagiovanna, Zahaf, Amina, Kassoussi, Abdelmoumen, Sharif, Ariane, Faure, Hélène, Traiffort, Elisabeth, and Ruat, Martial

Subjects
PLATELET-derived growth factor receptors, MYELIN basic protein, HEDGEHOG signaling proteins, CORPUS callosum, GENE expression, MYELIN proteins, OLIGODENDROGLIA
Abstract

Failure of myelin regeneration by oligodendrocytes contributes to progressive decline in many neurological diseases. Here, using in vitro and in vivo rodent models, functional blockade, and mouse brain demyelination, we demonstrate that Sonic hedgehog (Shh) expression in a subset of oligodendrocyte progenitor cells precedes the expression of myelin basic protein (MBP), a major myelin sheath protein. Primary cultures of rodent cortical oligodendrocytes show that Shh mRNA and protein are upregulated during oligodendrocyte maturation before the upregulation of MBP expression. Importantly, almost all MBP-positive cells are Shh positive during differentiation. During remyelination, we identify a rapid induction of Shh mRNA and peptide in oligodendroglial cells present in the demyelinated corpus callosum of mice, including a population of PDGFRα-expressing cells. Shh invalidation by an adeno-associated virus strategy demonstrates that the downregulation of Shh impairs the differentiation of oligodendrocytes in vitro and decreases MBP and myelin proteolipid protein expression in the demyelinated mouse brain at late stages of remyelination. We also report a parallel expression of Shh and MBP in oligodendroglial cells during early post-natal myelination of the mouse brain. Thus, we identify a crucial Shh signal involved in oligodendroglial cell differentiation and remyelination, with potential interest in the design of better-targeted remyelinating therapeutic strategies. [ABSTRACT FROM AUTHOR]

Published
2024
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5. Smoothened, Stem Cell Maintenance and Brain Diseases

Author

Ruat, Martial, Faure, Hélène, Daynac, Mathieu, Bernstein, Peter R., Series editor, Buschauer, Armin, Series editor, Georg, Gunda I., Series editor, Lowe, John A., Series editor, Stilz, Ulrich, Series editor, Supuran, Claudiu T., Series editor, Saxena, Anil Kumar, Series editor, and Ruat, Martial, editor

Published
2015
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6. Smoothened Inhibitors in Cancer

Author

Ruat, Martial, Hoch, Lucile, Bernstein, Peter R., Series editor, Buschauer, Armin, Series editor, Georg, Gunda I., Series editor, Lowe, John A., Series editor, Stilz, Ulrich, Series editor, Supuran, Claudiu T., Series editor, Saxena, Anil Kumar, Series editor, and Ruat, Martial, editor

Published
2015
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19. Smoothened/AMP-Activated Protein Kinase Signaling in Oligodendroglial Cell Maturation

Author

Del Giovane, Alice, primary, Russo, Mariagiovanna, additional, Tirou, Linda, additional, Faure, Hélène, additional, Ruat, Martial, additional, Balestri, Sonia, additional, Sposato, Carola, additional, Basoli, Francesco, additional, Rainer, Alberto, additional, Kassoussi, Abdelmoumen, additional, Traiffort, Elisabeth, additional, and Ragnini-Wilson, Antonella, additional

Published
2022
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25. PTH-independent regulation of blood calcium concentration by the calcium-sensing receptor

Author

Loupy, Alexandre, Ramakrishnan, Suresh Krishna, Wootla, Bharath, Chambrey, Regine, Faille, Renaud de la, Bourgeois, Soline, Bruneval, Patrick, Mandet, Chantal, Christensen, Erik Ilso, Faure, Helene, Cheval, Lydie, Laghmani, Kamel, Collet, Corinne, Eladari, Dominique, Dodd, Robert H., Ruat, Martial, and Houillier, Pascal

Subjects
Measurement, Research, Methods, Health aspects, Calcium (Nutrient) -- Health aspects -- Measurement, Parathyroid hormones -- Health aspects, Blood chemical analysis -- Methods, Gene expression -- Research, Parathyroid hormone -- Health aspects, Blood -- Analysis and chemistry, Calcium, Dietary -- Health aspects -- Measurement
Abstract

Introduction Calcium is the most abundant mineral in the human body, and its tight regulation is required for many critical biological functions, such as bone mineralization, muscle contraction, nerve conduction, [...], Tight regulation of calcium levels is required for many critical biological functions. The [Ca.sup.2+]-sensing receptor (CaSR) expressed by parathyroid cells controls blood calcium concentration by regulating parathyroid hormone (PTH) secretion. However, CaSR is also expressed in other organs, such as the kidney, but the importance of extraparathyroid CaSR in calcium metabolism remains unknown. Here, we investigated the role of extraparathyroid CaSR using thyroparathyroidectomized, PTH-supplemented rats. Chronic inhibition of CaSR selectively increased renal tubular calcium absorption and blood calcium concentration independent of PTH secretion change and without altering intestinal calcium absorption. CaSR inhibition increased blood calcium concentration in animals pretreated with a bisphosphonate, indicating that the increase did not result from release of bone calcium. Kidney CaSR was expressed primarily in the thick ascending limb of the loop of Henle (TAL). As measured by in vitro microperfusion of cortical TAL, CaSR inhibitors increased calcium reabsorption and paracellular pathway permeability but did not change NaCl reabsorption. We conclude that CaSR is a direct determinant of blood calcium concentration, independent of PTH, and modulates renal tubular calcium transport in the TAL via the permeability of the paracellular pathway. These findings suggest that CaSR inhibitors may provide a new specific treatment for disorders related to impaired PTH secretion, such as primary hypoparathyroidism.

Published
2012
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43. Molecular cloning, characterization, and localization of a high-affinity serotonin receptor (5-HT7) activating cAMP formation

Author

Ruat, Martial, Traiffort, Elisabeth, Leurs, Rob, Tardivel-Lacombe, Joel, Diaz, Jorge, Arrang, Jean-Michel, and Schwartz, Jean-Charles

Subjects
Circular DNA -- Research, Serotoninergic mechanisms -- Analysis, Serotonin -- Receptors, Science and technology
Abstract

The cloning of a cDNA which encodes a functional serotonin (5-HT) receptor, a neutrotransmitter representing the superfamily of G-protein-coupled receptors, is facilitated by employing a methodology underlined by a nucleotide sequence homology. The 5-HT receptor is suggested to be involved in the regulation of serotoninerigic functions associated with limbic brain divisions.

Published
1993

48. Expression of a cloned rat histamine H (sub 2) receptor mediating inhibitionof arachidonate release and activation of cAMP accumulation

Author

Traiffort, Elisabeth, Ruat, Martial, Arrang, Jean-Michel, Leurs, Rob, Piomelli, Daniele, and Schwartz, Jean-Charles

Subjects
Histamine receptors -- Research, Cyclic adenylic acid -- Research, Arachidonic acid -- Research, Science and technology
Abstract

A rat DNA segment encoding a protein homologous to canine H (sub 2) was cloned and transfected into Chinese hamster ovary cells. Transfected cells expressed the gene transcripts in a distribution consistent with that of H (sub2) receptors. Pharmacologic analysis show that stimulation of these H (sub 2) receptors results in cAMP accumulation. In addition, further studies show that receptor stimulation in the same cell also leads to inhibition of arachidonic release by a mechanism independent of cAMP and calcium levels. These results suggest that a single H (sub 2) receptor is involved in the regulation of adenylyl cyclase and phospholipase A (sub 2) activity.

Published
1992

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