Martial Ruat - Academia.edu (original) (raw)

Papers by Martial Ruat

Journal of Visualized Experiments, 2015

Neural stem cells (NSCs) in the subventricular zone of the lateral ventricles (SVZ) sustain olfac... more Neural stem cells (NSCs) in the subventricular zone of the lateral ventricles (SVZ) sustain olfactory neurogenesis throughout life in the mammalian brain. They successively generate transit amplifying cells (TACs) and neuroblasts that differentiate into neurons once they integrate the olfactory bulbs. Emerging fluorescent activated cell sorting (FACS) techniques have allowed the isolation of NSCs as well as their progeny and have started to shed light on gene regulatory networks in adult neurogenic niches. We report here a cell sorting technique that allows to follow and distinguish the cell cycle dynamics of the above-mentioned cell populations from the adult SVZ with a LeX/EGFR/CD24 triple staining. Isolated cells are then plated as adherent cells to explore in details their cell cycle progression by time-lapse video microscopy. To this end, we use transgenic Fluorescence Ubiquitination Cell Cycle Indicator (FUCCI) mice in which cells are red-fluorescent during G 1 phase due to a G 1 specific red-Cdt1 reporter. This method has recently revealed that proliferating NSCs progressively lengthen their G 1 phase during aging, leading to neurogenesis impairment. This method is easily transposable to other systems and could be of great interest for the study of the cell cycle dynamics of brain cells in the context of brain pathologies.

Thérapie, 2003

Le récepteur aux ions calcium extracellulaires (CaSR) appartient à la famille 3 des récepteurs co... more Le récepteur aux ions calcium extracellulaires (CaSR) appartient à la famille 3 des récepteurs couplés aux protéines G. Il contrôle la sécrétion de l'hormone parathyroïdienne (PTH) et joue un rôle clef dans la régulation de l'homéostasie calcique. Son activité est modulée par de faibles variations de la concentration des ions calcium (Ca 2+) et magnésium (Mg 2+) extracellulaires conduisant à la stimulation de la voie des phospholipases C et A2. Le développement récent de molécules de synthèse capables de potentialiser (calcimimétiques) les actions du Ca 2+ sur ce récepteur et de réduire la concentration de PTH circulant in vivo, suggère qu'il constitue une nouvelle cible thérapeutique pour le traitement des hyperparathyroïdies primaires et secondaires. Son blocage par un antagoniste (calcilytique) stimule la sécrétion de PTH et pourrait être mis à profit pour le traitement de l'ostéoporose. Ce récepteur est aussi exprimé dans d'autres tissus tels que la thyroïde, les reins, l'os ou encore dans des populations neuronales et gliales, où il participerait aux réponses cellulaires complexes induites par les ions Ca 2+ et Mg 2+ présents dans les fluides extracellulaires.

Proceedings of the National Academy of Sciences, 1996

Heme oxygenase 2 (HO-2), which synthesizes carbon monoxide (CO), has been localized by immunohist... more Heme oxygenase 2 (HO-2), which synthesizes carbon monoxide (CO), has been localized by immunohistochemistry to endothelial cells and adventitial nerves of blood vessels. HO-2 is also localized to neurons in autonomic ganglia, including the petrosal, superior cervical, and nodose ganglia, as well as ganglia in the myenteric plexus of the intestine. Enzyme studies demonstrated that tin protoporphyrin-9 is a selective inhibitor of HO with approximately 10-fold selectivity for HO over endothelial nitric oxide synthase (NOS) and soluble guanylyl cyclase. Inhibition of HO activity by tin protoporphyrin 9 reverses the component of endothelial-derived relaxation of porcine distal pulmonary arteries not reversed by an inhibitor of NOS. Thus, CO, like NO, may have endothelial-derived relaxing activity. The similarity of NOS and HO-2 localizations and functions in blood vessels and the autonomic nervous system implies complementary and possibly coordinated physiologic roles for these two media...

Experimental Cell Research, 2007

Oligodendrocytes (OLs) are the glial cells of the central nervous system (CNS) classically known ... more Oligodendrocytes (OLs) are the glial cells of the central nervous system (CNS) classically known to be devoted to the formation of myelin sheaths around most axons of the vertebrate brain. We have addressed the role of these cells during cerebellar development, by ablating OLs in vivo. Previous analyses had indicated that OL ablation during the first six postnatal days results into a striking cerebellar phenotype, whose major features are a strong reduction of granule neurons and aberrant Purkinje cells development. These two cell types are highly interconnected during cerebellar development through the production of molecules that help their proliferation, differentiation and maintenance. In this article, we present data showing that OL ablation has major effects on the physiology of Purkinje (PC) and granule cells (GC). In particular, OL ablation results into a reduction of sonic hedgehog (Shh), Brain Derived Neurotrophic Factor (BDNF), and Reelin (Rln) expression. These results indicate that absence of OLs profoundly alters the normal cerebellar developmental program.

Biophysical Journal, 2011

Intrinsically disordered proteins undergo conformational changes that are often beyond the scope ... more Intrinsically disordered proteins undergo conformational changes that are often beyond the scope of current computational techniques used to study the dynamics of folded proteins. New approaches to define a metric for the dynamics of disordered proteins have been developed which are also readily applicable to the study of non-equilibrium globular protein dynamics. We use dimensionality reduction and clustering techniques applied to molecular dynamics (MD) simulations of a class of entirely disordered proteins (outside of a small anchoring domain) involved in nucleocytoplasmic transport, the FG-nucleoporins (FGnups), as well as folding simulations of several globular proteins of similar size and sequence composition to compare disordered protein dynamics to early-stage folding dynamics. Our results provide detailed maps of the protein conformation space, allow us to classify proteins based on their dynamics, and indicate that disordered protein motion is of higher-dimensionality than earlystage folding dynamics.

Information about reprints can be found online at: Reprints: document. Permissions and Rights Que... more Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer about this process is available in the located, click Request Permissions in the middle column of the Web page under Services. Further information Editorial Office. Once the online version of the published article for which permission is being requested is can be obtained via RightsLink, a service of the Copyright Clearance Center, not theCirculation Researchin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on March 4,

La presente invention concerne donc les diamines de formule generale (I) : (CF DESSIN DANS BOPI) ... more La presente invention concerne donc les diamines de formule generale (I) : (CF DESSIN DANS BOPI) dans laquelle : A represente un groupe A1 ou A2 de formule generale suivante : (CF DESSIN DANS BOPI) B represente un groupe B1 ou B2 de formule generale suivante : (CF DESSIN DANS BOPI) X represente un groupe SO2 , CH2 , C=O ou COO, (CF DESSIN DANS BOPI) represente un groupe deformule CH (R25) -CH (R26) ou CH (R27) =CH (R28) et R1 a R28, identiques ou differents, representent, independamment l'un de l'autre, un atome d'hydrogene oud'halogene ou un groupe alkyle, cycloalkyle, CN, NO2 , hydroxy, aryle, aralkyle, alcoxy, aryloxy, amino, alkylamino, dialkylamino, cycloalkylamino, arylamino, arylalkylamino, diarylamino, diarylalkylamino, trihalogenoalkyle ou trihalogenoalcoxy, a la condition que dans le groupe A1, au moins un des radicaux R1, R2, R3, R4 ou R5 represente l'atome d'hydrogene lorsque les quatre autres ne representent pas l'atome d'hydrogene et dan...

International Journal of Developmental Neuroscience, 2006

Neuroscience, 2000

Bone morphogenetic proteins belong to the transforming growth factor-b superfamily and act throug... more Bone morphogenetic proteins belong to the transforming growth factor-b superfamily and act through serine/threonine kinase type I and type II receptors such as bone morphogenetic protein receptor type I and type II. In order to further understand the roles that these factors exert in the nervous system, we have examined the expression pattern of seven bone morphogenetic proteins and bone morphogenetic protein receptor type I and II transcripts in the brain and spinal cord of rodent. Whereas bone morphogenetic protein receptor type I expression was low in rat brain, in situ hybridization studies performed with specific digoxigeninlabelled riboprobes revealed the presence of bone morphogenetic protein receptor type II-positive cells throughout the brain, with a notable localization in dopaminergic cells of the substantia nigra. Bone morphogenetic protein receptor type II transcripts were also expressed by large motoneuron-like cells located in the ventral horn of the spinal cord and by sensory neurons of dorsal root ganglia. In addition, we observed a significant up-regulation of bone morphogenetic protein receptor type II in the granule cells of the dentate gyrus 48 h after transient global cerebral ischemia in rat suggesting that modulation of this receptor intervenes during neuronal plasticity or repair that occur upon brain injury. Among the potential ligands for this receptor, bone morphogenetic protein-6 and bone morphogenetic protein-7 were expressed in meninges and the choroid plexus, while bone morphogenetic protein-4-expressing cells were spatially and temporally regulated in myelinated structures during development and in the adult suggesting its expression in oligodendrocytes. These data clearly indicate that besides their roles in bone and embryonic tissues, bone morphogenetic proteins and their receptors may have also important functions in adult neural tissues.

NeuroReport, 2005

Institut des maladies rares, La Ligue contre le Cancer and Fondation pour la Recherche sur le Cer... more Institut des maladies rares, La Ligue contre le Cancer and Fondation pour la Recherche sur le Cerveau (FRC). K.L. is the recipient of a doctoral fellowship from the 'Ministe' re de la Recherche', and from La Ligue contre le Cancer and Association pour la Recherche contre le Cancer.

Molecular Aspects of Medicine, 2013

The Na +-independent, high affinity choline carrier system proposed to supply choline for the syn... more The Na +-independent, high affinity choline carrier system proposed to supply choline for the synthesis of cell membrane phospholipids was recently associated with SLC44 family members (SLC44A1-5) also called choline-like transporter family. SLC44A1 is widely expressed throughout the nervous system in both neurons and oligodendrocytes, while SLC44A2-4 are mainly detected in peripheral tissues. The subcellular localization of the proteins was mainly addressed for SLC44A1 through the development of specific antibodies. SLC44A1 is detected in both the plasma and mitochondrial membranes where the protein is able to transport choline at high affinity and in a Na +-independent manner. The physiological relevance of SLC44A1 as a choline carrier is indicated by its likely involvement in membrane synthesis for cell growth or repair, and also by its role in phospholipid production for the generation of lung surfactant. Moreover, an autoimmune disease has been related to the blockade of SLC44A2 function, which results in the alteration of hair cells in the inner ear and leads to autoimmune hearing loss. In the alloimmune syndrome called transfusion-related acute lung injury, antibodies to SLC44A2 cause a deleterious aggregation of granulocytes. Therefore transporters of the SLC44 family represent attractive and promising targets for therapeutic and diagnostic applications regarding both immune and degenerative diseases.

Journal of Neurochemistry, 2010

The discovery of a Sonic Hedgehog (Shh) signaling pathway in the mature vertebrate CNS has paved ... more The discovery of a Sonic Hedgehog (Shh) signaling pathway in the mature vertebrate CNS has paved the way to the characterization of the functional roles of Shh signals in normal and diseased brain. Shh is proposed to participate in the establishment and maintenance of adult neurogenic niches and to regulate the proliferation of neuronal or glial precursors in several brain areas. Consistent with its role during brain development, misregulation of Shh signaling is associated with tumorigenesis while its recruitement in damaged neural tissue might be part of the regenerating process. This review focuses on the most recent data of the Hedgehog pathway in the adult brain and its relevance as a novel therapeutic approach for brain diseases including brain tumors.

Journal of Neurochemistry, 2005

We show here that the choline transporter-like (CTL) family is more extensive than initially desc... more We show here that the choline transporter-like (CTL) family is more extensive than initially described with five genes in humans and complex alternative splicing. In adult rat tissues, CTL2-4 mRNAs are mainly detected in peripheral tissues, while CTL1 is widely expressed throughout the nervous system. During rat post-natal development, CTL1 is expressed in several subpopulations of neurones and in the white matter, where its spatio-temporal distribution profile recalls that of myelin basic protein, an oligodendrocyte marker. We identified two major rat splice variants of CTL1 (CTL1a and CTL1b) differing in their carboxy-terminal tails with both able to increase choline transport after transfection in neuroblastoma cells. In the developing brain, CTL1a is expressed in both neurones and oligodendroglial cells, whereas CTL1b is restricted to oligodendroglial cells. These findings suggest specific roles for CTL1 splice variants in both neuronal and oligodendrocyte physiology.

Journal of Neurochemistry, 1992

HI receptors from guinea pig cerebellum were solubilized using digitonin, and [1251]iodobolpyrami... more HI receptors from guinea pig cerebellum were solubilized using digitonin, and [1251]iodobolpyramine was used as a probe. [ 1251]Iodobolpyramine binding to this solubilized preparation occurred with a KD of 0.1 nM and a B,, of 220 fmol/mg of protein and was inhibited by various HI ligands

Journal of Neurochemistry, 1989

The photoaffinity probe [125I]iodoazidophenpyramine was used to label irreversibly the H1-recepto... more The photoaffinity probe [125I]iodoazidophenpyramine was used to label irreversibly the H1-receptor in membranes of several guinea pig brain regions and of the cerebral cortex of the rat, mouse, and pig. Following sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, two main bands were specifically labeled in all tissues: a 56-kilodalton (kDa) peptide and a 41-47-kDa peptide whose relative importance diminished in the presence of protease inhibitors. This indicates that, in all tissues examined, in spite of evidence for pharmacological heterogeneity, the ligand recognition domain of the H1-receptor resides in a 56-kDa peptide.

Journal of Neurochemistry, 2006

Sonic hedgehog signaling is required for the maintenance of stem cell niches in the postnatal sub... more Sonic hedgehog signaling is required for the maintenance of stem cell niches in the postnatal subventricular zone and the proliferation of neural progenitors in the mature hippocampus. We show here that delivery of Sonic hedgehog protein into the lateral ventricle of adult mice increases cell proliferation in the corpus callosum and cerebral cortex. In this latter area, the number of neural progenitors expressing the proteoglycan NG2 is enhanced 2 days after the injection. In both areas, mRNA up-regulation of the transcriptional target gene Patched was observed in cells expressing the oligodendroglial transcription factor Olig1. Twenty-six days following the adenovirus-mediated delivery of Sonic hedgehog into the lateral ventricle, newly generated cells in the cerebral cortex and in the corpus callosum are influenced towards the initial steps of oligodendrogenesis, as indicated by a 50% increase in the number of cells expressing the oligodendroglial marker DM20. Our experiments demonstrate that the number of oligodendrocyte precursor cells in the cerebral cortex and corpus callosum can be increased upon delivery of Sonic hedgehog proteins and highlight the potential capacity of the adult brain to mobilize a pool of premyelinating cells.

Journal of Cellular and Molecular Medicine, 2009

Bone loss associated with aging, oestrogen deficiency, immobilization or glucocorticoid treatment... more Bone loss associated with aging, oestrogen deficiency, immobilization or glucocorticoid treatment is characterized by insufficient bone formation relative to resorption, resulting in negative bone balance, alterations of bone mass and increased incidence of fractures [1, 2]. The available anti-osteoporotic drugs act by decreasing bone resorption or promoting bone formation, thereby resulting in increased bone mass and reduced fracture incidence in patients with osteoporosis [2]. The di-strontium salt strontium ranelate is a new anti-osteoporotic drug. In postmenopausal osteoporotic women, strontium ranelate (2 g/day) was found to reduce the risk of vertebral fracture, non-vertebral fracture and hip fracture over 3 years [3,4]. Strontium ranelate was reported to act by inhibiting bone resorption and promoting bone formation [5], thereby inducing a positive bone balance in experimental osteopenic models [6, 7] and in patients with postmenopausal osteoporosis [3-5, 8]. Previous studies indicate that strontium ranelate may act on osteoblasts to promote cell activity and differentiation [9-12]. Notably, others and we showed that strontium ranelate can activate cell replication in rodent calvaria osteoblasts, resulting in stimulation of collagen synthesis [9,13]. However, the cellular mechanisms involved in the effects of strontium ranelate in osteoblasts are not fully understood. One attractive hypothesis Calcium sensing receptor-dependent and receptor-independent activation of osteoblast replication and survival by strontium ranelate

Human Genetics, 1994

We have assigned the human histamine H1-receptor gene to chromosome 3 by Southern blot analysis o... more We have assigned the human histamine H1-receptor gene to chromosome 3 by Southern blot analysis of a chromosome mapping panel constructed from human-hamster somatic cell hybrids. This assignment was confirmed by in situ hybridization on metaphase chromosomes and involved bands 3p14-p21.