References of "Moonen, Gustave"
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See detailChemical inhibitors of cyclin-dependent kinases control proliferation, apoptosis and differentiation of oligodendroglial cells
Nguyen, Laurent ULg; Malgrange, Brigitte ULg; Rocher, Véronique et al

in International Journal of Developmental Neuroscience (2003), 21(6), 321-326

Since cyclin-dependent kinases (Cdks) and their endogenous inhibitors (Cdkis) play an essential role as regulators of cell cycle withdrawal and onset of differentiation within oligodendroglial cells, we ... [more ▼]

Since cyclin-dependent kinases (Cdks) and their endogenous inhibitors (Cdkis) play an essential role as regulators of cell cycle withdrawal and onset of differentiation within oligodendroglial cells, we assessed here the effects of exogenous chemical Cdk inhibitors (CKIs) on cultured rat cortical oligodendrocyte progenitor cells (OPCs). We showed that purine derivatives and especially roscovitine strongly inhibited OPCs proliferation. In the presence of mitogenic signals, roscovitine synergized with thyroid hormone to stimulate oligodendrocyte differentiation. Roscovitine also prevented oligodendroglial apoptosis induced by growth factor deprivation. We thus demonstrated that small molecular weight chemical CKIs have important effects on crucial events of oligodendroglial development in vitro. This might open prospects for using these apparently well tolerated agents in remyelination strategies. (C) 2003 ISDN. Published by Elsevier Ltd. All rights reserved. [less ▲]

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See detailUntangling the functional potential of PSA-NCAM-expressing cells in CNS development and brain repair strategies
Nguyen, Laurent ULg; Rigo, Jean-Michel; Malgrange, Brigitte ULg et al

in Current Medicinal Chemistry (2003), 10(20), 2185-2196

Central nervous system (CNS) neural stem cells (NSCs), which are mostly defined by their ability to self-renew and to generate the three main cell lineages of the CNS, were isolated from discrete regions ... [more ▼]

Central nervous system (CNS) neural stem cells (NSCs), which are mostly defined by their ability to self-renew and to generate the three main cell lineages of the CNS, were isolated from discrete regions of the adult mammalian CNS including the subventricular zone (SVZ) of the lateral ventricle and the dentate gyrus in the hippocampus. At early stages of CNS cell fate determination, NSCs give rise to progenitors that express the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). PSA-NCAM(+) cells persist in adult brain regions where neuronal plasticity and sustained formation of new neurons occur. PSA-NCAM, has been shown to be involved in the regulation of CNS myelination as well as in changes of cell morphology that are necessary for motility, axonal guidance, synapse formation, and functional plasticity in the CNS. Although being preferentially committed to a restricted either glial or neuronal fate, cultured PSA-NCAM(+) progenitors do preserve a relative degree of multipotentiality. Considering that PSA-NCAM(+) cells can be neatly used for brain repair purposes, there is much interest for studying signaling factors regulating their development. With this regard, it is noteworthy that neurotransmitters, which belong to the micro-environment of neural cells in vivo, regulate morphogenetic events preceding synaptogenesis such as cell proliferation, migration, differentiation and death. Consistently, several ionotropic but also G-protein-coupled neurotransmitter receptors were found to be expressed in CNS embryonic and postnatal progenitors. In the present review, we outlined the ins and outs of PSA-NCAM(+) cells addressing to what extent our understanding of extrinsic and in particular neurotransmitter-mediated signaling in these CNS precursor cells might represent a new leading track to develop alternative strategies to stimulate brain repair. [less ▲]

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See detailImage analysis of the axonal ingrowth into poly(D,L-lactide) porous scaffolds in relation to the 3-D porous structure
Blacher, Silvia ULg; Maquet, Véronique; Luyckx, Françoise ULg et al

in Biomaterials (2003), 24(6), 1033-1040

Porous polymer scaffolds are promising materials for neural tissue engineering because they offer valuable three-dimensional (3D) supports for the in vitro and in vivo axonal growth and tissue expansion ... [more ▼]

Porous polymer scaffolds are promising materials for neural tissue engineering because they offer valuable three-dimensional (3D) supports for the in vitro and in vivo axonal growth and tissue expansion. At the time being, how the in vivo neuronal cell development depends on the scaffold 3-D architecture is unknown. Therefore, scanning electron micrographs of longitudinal sections of porous polylactide scaffolds and immunohistological sections of these scaffolds after implantation and neurofilament staining have been studied by image analysis. Pore orientation and axonal ingrowth have been investigated by spectral analysis on gray level SEM images. Binary image processing has been carried out and the binary images have been studied by spectral analysis in order to estimate the possible effect of the image noise on the real pattern. In addition to axonal orientation, density and length distribution of the regenerated axons into the polymer scaffold have been measured. Dependence of the axonal ingrowth on the 3D-polymer scaffold has been discussed on the basis of the collected data. (C) 2002 Elsevier Science Ltd. All rights reserved. [less ▲]

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See detailEffects of Alzheimer's disease on the recognition of novel versus familiar words : Neuropsychological and clinico-metabolic data
Lekeu, Françoise ULg; Van der Linden, Martial ULg; Degueldre, Christian ULg et al

in Neuropsychology (2003), 17(1), 143-154

This study explored recognition memory performance for novel versus familiar words in Alzheimer's disease (AD) patients and normal controls (NCs), using an adaptation of E. Tulving and N. Kroll's (1995 ... [more ▼]

This study explored recognition memory performance for novel versus familiar words in Alzheimer's disease (AD) patients and normal controls (NCs), using an adaptation of E. Tulving and N. Kroll's (1995) procedure. Results showed that both groups exhibited more hits and more false alarms for familiar than for novel words. The groups did not differ in the recognition of familiar words, reflecting preserved familiarity processes in AD. However, AD patients made more false alarms than NCs in the recognition of novel words, reflecting impairment of recollection processes in AD. A positron emission tomography analysis of clinico-metabolic correlations in AD patients showed a correlation between recognition of novel words and right hippocampal activity, whereas recognition of familiar words was more related to metabolic activity in the left posterior orbitofrontal cortex. [less ▲]

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See detailAutocrine/paracrine activation of the GABA(A) receptor inhibits the proliferation of neurogenic polysialylated neural cell adhesion molecule-positive (PSA-NCAM+) precursor cells from postnatal striatum.
Nguyen, Laurent ULg; Malgrange, Brigitte ULg; Breuskin, Ingrid ULg et al

in Journal of Neuroscience (2003), 23(8), 3278-94

GABA and its type A receptor (GABA(A)R) are present in the immature CNS and may function as growth-regulatory signals during the development of embryonic neural precursor cells. In the present study, on ... [more ▼]

GABA and its type A receptor (GABA(A)R) are present in the immature CNS and may function as growth-regulatory signals during the development of embryonic neural precursor cells. In the present study, on the basis of their isopycnic properties in a buoyant density gradient, we developed an isolation procedure that allowed us to purify proliferative neural precursor cells from early postnatal rat striatum, which expressed the polysialylated form of the neural cell adhesion molecule (PSA-NCAM). These postnatal striatal PSA-NCAM+ cells were shown to proliferate in the presence of epidermal growth factor (EGF) and formed spheres that preferentially generated neurons in vitro. We demonstrated that PSA-NCAM+ neuronal precursors from postnatal striatum expressed GABA(A)R subunits in vitro and in situ. GABA elicited chloride currents in PSA-NCAM+ cells by activation of functional GABA(A)R that displayed a typical pharmacological profile. GABA(A)R activation in PSA-NCAM+ cells triggered a complex intracellular signaling combining a tonic inhibition of the mitogen-activated protein kinase cascade and an increase of intracellular calcium concentration by opening of voltage-gated calcium channels. We observed that the activation of GABA(A)R in PSA-NCAM+ neuronal precursors from postnatal striatum inhibited cell cycle progression both in neurospheres and in organotypic slices. Furthermore, postnatal PSA-NCAM+ striatal cells synthesized and released GABA, thus creating an autocrine/paracrine mechanism that controls their proliferation. We showed that EGF modulated this autocrine/paracrine loop by decreasing GABA production in PSA-NCAM+ cells. This demonstration of GABA synthesis and GABA(A)R function in striatal PSA-NCAM+ cells may shed new light on the understanding of key extrinsic cues that regulate the developmental potential of postnatal neuronal precursors in the CNS. [less ▲]

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See detailBrain correlates of performance in a free/cued recall task with semantic encoding in Alzheimer disease
Lekeu, Françoise ULg; Van der Linden, Martial ULg; Chicherio, C. et al

in Alzheimer Disease and Associated Disorders (2003), 17(1), 35-45

The goal of this study was to explore in patients with Alzheimer's disease (AD) the brain correlates of free and cued recall performance using an adaptation of the procedure developed by Grober and ... [more ▼]

The goal of this study was to explore in patients with Alzheimer's disease (AD) the brain correlates of free and cued recall performance using an adaptation of the procedure developed by Grober and Buschke (1987). This procedure, which ensures semantic processing and coordinates encoding and retrieval, has been shown to be very sensitive to an early diagnosis of AD. Statistical parametric mapping (SPM 99) was used to establish clinicometabolic correlations between performance at free and cued verbal recall and resting brain metabolism in 31 patients with AD. Results showed that patient's score on free recall correlated with metabolic activity in right frontal regions (BA 10 and BA 45), suggesting that performance reflected a strategic retrieval attempt. Poor retrieval performance was tentatively attributed to a loss of functional correlation between frontal and medial temporal regions in patients with AD compared with elderly controls. Performance on cued recall was correlated to residual metabolic activity in bilateral parahippocampal regions (BA 36), suggesting that performance reflected retrieval of semantic associations, without recollection in AD. In conclusion, this study demonstrates that the diagnostic sensitivity for Alzheimer's disease of the cued recall performance in the Grober and Buschke procedure (1987) depends on the activity of parahippocampal regions, one of the earliest targets of the disease. Moreover, the results suggest that the poor performance of patients with AD during free and cued recall is related to a decreased connectivity between parahippocampal regions and frontal areas. [less ▲]

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See detailRegulation of neural markers nestin and GFAP expression by cultivated bone marrow stromal cells.
Wislet-Gendebien, Sabine ULg; Leprince, Pierre ULg; Moonen, Gustave ULg et al

in Journal of Cell Science (2003), 116(Pt 16), 3295-302

Bone marrow stromal cells can differentiate into many types of mesenchymal cells, i.e. osteocyte, chondrocyte and adipocyte, but can also differentiate into non-mesenchymal cells, i.e. neural cells under ... [more ▼]

Bone marrow stromal cells can differentiate into many types of mesenchymal cells, i.e. osteocyte, chondrocyte and adipocyte, but can also differentiate into non-mesenchymal cells, i.e. neural cells under appropriate in vivo experimental conditions (Kopen et al., 1999; Brazelton et al., 2000; Mezey et al., 2000). This neural phenotypic plasticity allows us to consider the utilization of mesenchymal stem cells as cellular material in regenerative medicine. In this study, we demonstrate that cultured adult rat stromal cells can express nestin, an intermediate filament protein predominantly expressed by neural stem cells. Two factors contribute to the regulation of nestin expression by rat stromal cells: serum in the culture medium inhibits nestin expression and a threshold number of passages must be reached below which nestin expression does not occur. Only nestin-positive rat stromal cells are able to form spheres when they are placed in the culture conditions used for neural stem cells. Likewise, only nestin-positive stromal cells are able to differentiate into GFAP (glial fibrillary acidic protein)-positive cells when they are co-cultivated with neural stem cells. We thus demonstrated that adult rat stromal cells in culture express nestin in absence of serum after passaging the cells at least ten times, and we suggest that nestin expression by these cells might be a prerequisite for the acquisition of the capacity to progress towards the neural lineage. [less ▲]

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See detailBrain function in the vegetative state
Laureys, Steven ULg; Antoine, S.; Boly, Mélanie ULg et al

in Acta Neurologica Belgica (2002), 102(4), 177-185

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates ... [more ▼]

Positron emission tomography (PET) techniques represent a useful tool to better understand the residual brain function in vegetative state patients. It has been shown that overall cerebral metabolic rates for glucose are massively reduced in this condition. However, the recovery of consciousness from vegetative state is not always associated with substantial changes in global metabolism. This finding led us to hypothesize that some vegetative patients are unconscious not just because of a global loss of neuronal function, but rather due to an altered activity in some critical brain regions and to the abolished functional connections between them. We used voxel-based Statistical Parametric Mapping (SPM) approaches to characterize the functional neuroanatomy of the vegetative state. The most dysfunctional brain regions were bilateral frontal and parieto-temporal associative cortices. Despite the metabolic impairment, external stimulation still induced a significant neuronal activation (i.e., change in blood flow) in vegetative patients as shown by both auditory click stimuli and noxious somatosensory stimuli. However this activation was limited to primary cortices and dissociated from higher-order associative cortices, thought to be necessary for conscious perception. Finally, we demonstrated that vegetative patients have impaired functional connections between distant cortical areas and between the thalami and the cortex and, more importantly, that recovery of consciousness is paralleled by a restoration of this cortico-thalamo-cortical interaction. [less ▲]

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See detailExploring the effect of action familiarity on SPTs recall performance in Alzheimer's disease
Lekeu, Françoise ULg; Van der Linden, Martial ULg; Moonen, Gustave ULg et al

in Journal of Clinical & Experimental Neuropsychology (2002), 24(8), 1057-1069

This study examined the performance of normal controls (NC) and Alzheimer's disease (AD) patients on free recall, semantic cued recall and object cued recall of both subject-performed tasks (SPTs) and ... [more ▼]

This study examined the performance of normal controls (NC) and Alzheimer's disease (AD) patients on free recall, semantic cued recall and object cued recall of both subject-performed tasks (SPTs) and verbal descriptions of actions, by controlling familiarity of actions associated to objects. The results showed that both groups performed better after SPT encoding than after verbal encoding. in all three types of recall. In addition, this SPT advantage was greater for AD patients than for NC in the object cued recall test, emphasizing AD patients' sensibility to the congruence of cues between encoding and retrieval conditions. Following verbal encoding. NC showed a better recall for less familiar actions than for highly familiar actions, whereas AD patients exhibited the opposite pattern. These results reflect that AD patients did not benefit from a distinctiveness effect at encoding for improving subsequent retrieval of verbal information, probably due to a reduced level of elaboration during encoding. However, there was no effect of action familiarity on recall performance by both groups following SPT encoding. These results suggest that memory for verbal actions and SPTs is governed by different principles. In addition. they demonstrate the robustness of the SPT effect in AD patients, who were able to improve memory performance in the SPT condition not only with highly familiar actions but also with less familiar actions. [less ▲]

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See detailEpithelial supporting cells can differentiate into outer hair cells and Deiters' cells in the cultured organ of Corti
Malgrange, Brigitte ULg; Thiry, Marc ULg; Van De Water, Thomas R. et al

in Cellular and Molecular Life Sciences : CMLS (2002), 59(10), 1744-1757

The organ of Corti is a complex structure containing a single row of inner hair cells (IHCs) and three rows of outer hair cells (OHCs), supported respectively by one row of inner phalangeal cells and ... [more ▼]

The organ of Corti is a complex structure containing a single row of inner hair cells (IHCs) and three rows of outer hair cells (OHCs), supported respectively by one row of inner phalangeal cells and three rows of Deiters' cells. When fetal rat organ of Corti explants are cultured, supernumerary OHCs and supernumerary Deiters' cells are produced, without any additional cell proliferation. Analysis of semi- and ultrathin sections revealed that supernumerary OHCs are produced at the distal edge of the organ of Corti. Quantitative analysis of cell types present in the organ of Corti demonstrates that when the number of OHCs increases: (i) the total number of cells remains constant; (ii) the number of Deiters' cells increases; (iii) the number of tectal cells decreases and of Hensen's cells decreases. Using specific HC markers, i.e. jagged2 (Jag2) and Math1, we showed that in addition to existing OHCs, supernumerary OHCs, tectal cells and Hensen's cells expressed these markers in embryonic day 19 organ of Corti explants after 5 days in vitro. The results of this study suggest that Hensen's cells retain the capacity to differentiate into either tectal cells, which differentiate into OHCs, or into undertectal cells which differentiate into Deiters' cells. [less ▲]

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See detailCortical processing of noxious somatosensory stimuli in the persistent vegetative state
Laureys, Steven ULg; Faymonville, Marie-Elisabeth ULg; Peigneux, Philippe ULg et al

in NeuroImage (2002), 17(2), 732-741

The persistent vegetative state (PVS) is a devastating medical condition characterized by preserved wakefulness contrasting with absent voluntary interaction with the environment. We used positron ... [more ▼]

The persistent vegetative state (PVS) is a devastating medical condition characterized by preserved wakefulness contrasting with absent voluntary interaction with the environment. We used positron emission tomography to assess the central processing of noxious somatosensory stimuli in the PVS. Changes in regional cerebral blood flow were measured during high-intensity electrical stimulation of the median nerve compared with rest in 15 nonsedated patients and in 15 healthy controls. Evoked potentials were recorded simultaneously. The stimuli were experienced as highly unpleasant to painful in controls. Brain glucose metabolism was also studied with [F-18]fluorodeoxyglucose in resting conditions. In PVS patients, overall cerebral metabolism was 40% of normal values. Nevertheless, noxious somatosensory stimulation-activated midbrain, contralateral thalamus, and primary somatosensory cortex in each and every PVS patient, even in the absence of detectable cortical evoked potentials. Secondary somatosensory, bilateral insular, posterior parietal, and anterior cingulate cortices did not show activation in any patient. Moreover, in PVS patients, the activated primary somatosensory cortex was functionally disconnected from secondary somatosensory, bilateral posterior parietal, premotor, polysensory superior temporal, and prefrontal cortices. In conclusion, somatosensory stimulation of PVS patients, at intensities that elicited pain in controls, resulted in increased neuronal activity in primary somatosensory cortex, even if resting brain metabolism was severely impaired. However, this activation of primary cortex seems to be isolated and dissociated from higher-order associative cortices. (C) 2002 Elsevier Science (USA). [less ▲]

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See detailIdentification of factors that maintain mammalian outer hair cells in adult organ of Corti explants
Malgrange, Brigitte ULg; Rigo, Jean-Michel; Coucke, Paul et al

in Hearing Research (2002), 170(1-2), 48-58

Both outer hair cells (OHCs) and inner hair cells (IHCs) survive and mature in 3 days old rat organ of Corti explants cultured for I month in a minimal essential medium. In contrast. under the same ... [more ▼]

Both outer hair cells (OHCs) and inner hair cells (IHCs) survive and mature in 3 days old rat organ of Corti explants cultured for I month in a minimal essential medium. In contrast. under the same culture conditions, only IHCs survive in explants from adult guinea pig organ of Corti while many of the OHCs are lost within the first 48 It. Hair cell Count,, show OHCs loss to be greater in the lower portion (i.e. middle turn) of the cochlea than Lit the apex. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) indicates that there is DNA damage in adult OHCs, within 8 h of explantation. Treatment of the adult organ of Corti explants with either actinomycin D (10(-7) M) or cycloheximide (10(-6) M) prevents most OHC losses . According to these results apoptosis may be the mechanism of OHC loss in adult organ of Corti explants, Stable membrane potentials recorded from the OHCs in both uncultured and actinomycin D-treated organ of Corti explants cultured for 72 h demonstrate the functional integrity of these hair cells. OHC losses in the adult guinea pig, organ of Corti cultures can also be prevented by treatment with several of the growth factors tested. i.e. acidic fibroblast growth factor (aFGF), insulin-like growth factor-1 (IGF-1), epidermal growth factor (EGF), transforming growth factor-beta1 (TGF-beta1). and glial cell-derived neurotrophic factor (GDNF). The results of this study suggest that growth factor therapy may be applicable to the treatment of some hearing disorders. (C) 2002 Elsevier Science B.V. All rights reserved. [less ▲]

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See detailThe anti-epileptic drug levetiracetam reverses the inhibition by negative allosteric modulators of neuronal GABA- and glycine-gated currents
Rigo, Jean-Michel; Hans, Grégory ULg; Nguyen, Laurent ULg et al

in British Journal of Pharmacology (2002), 136(5), 659-672

1 In this study in vitro and in vivo approaches were combined in order to investigate if the anti-epileptic mechanism(s) of action of levetiracetam (LEV; Keppra(R)) may involve modulation of inhibitory ... [more ▼]

1 In this study in vitro and in vivo approaches were combined in order to investigate if the anti-epileptic mechanism(s) of action of levetiracetam (LEV; Keppra(R)) may involve modulation of inhibitory neurotransmission. 2 GABA- and glycine-gated currents were studied in vitro using whole-cell patch-clamp techniques applied on cultured cerebellar granule, hippocampal and spinal neurons. Protection against clonic convulsions was assessed in vivo in sound-susceptible mice. The effect of LEV was compared with reference anti-epileptic drugs (AEDs): carbamazepine, phenytoin, valproate, clonazepam, phenobarbital and ethosuximide. 3 LEV contrasted the reference AEDs by an absence of any direct effect on glycine-gated currents. At high concentrations, beyond therapeutic relevance, it induced a small reduction in the peak amplitude and a prolongation of the decay phase of GABA-gated currents. A similar action on GABA-elicited currents was observed with the reference AEDs, except ethosuximide. 4 These minor direct effects contrasted with a potent ability of LEV (EC50 = 1-10 muM) to reverse the inhibitory effects of the negative allosteric modulators zinc and beta-carbolines on both GABA(A) and glycine receptor-mediated responses. 5 Clonazepam, phenobarbital and valproate showed a similar ability to reverse the inhibition of beta-carbolines on GABA-gated currents. Blockade of zinc inhibition of GABA responses was observed with clonazepam and ethosuximide. Phenytoin was the only AED together with LEV that inhibited the antagonism of zinc on glycine-gated currents and only clonazepam and phenobarbital inhibited the action of DMCM. 6 LEV (17 mg kg(-1)) produced a potent suppression of sound-induced clonic convulsions in mice. This protective effect was significantly abolished by co-administration of the beta-carboline FG 7142, from a dose of 5 mg kg(-1). In contrast, the benzodiazepine receptor antagonist flumazenil (up to 10 mg kg(-1)) was without any effect on the protection afforded by LEV. 7 The results of the present study suggest that a novel ability to oppose the action of negative modulators on the two main inhibitory ionotropic receptors may be of relevance for the anti-epileptic mechanism(s) of action of LEV. [less ▲]

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See detailNestin expression in cultivated mesenchymal stem cells: Regulation and potential role in their neural differentiation
Wislet-Gendebien, Sabine ULg; Leprince, Pierre ULg; Moonen, Gustave ULg et al

in Glia (2002, May), (Suppl. 1), 87

Bone marrow stromal cells can differentiate into many types of mesenchymal cells, i.e. osteocyte, chondrocyte, fibroblast and adipocyte, but can also differentiate into non-mesenchymal cell, i.e. neural ... [more ▼]

Bone marrow stromal cells can differentiate into many types of mesenchymal cells, i.e. osteocyte, chondrocyte, fibroblast and adipocyte, but can also differentiate into non-mesenchymal cell, i.e. neural cells in appropriate in vivo experimental conditions (Kopen and al.,PNAS,96, 10711,1999, Brazelton and al, Science, 290,1175, 2000, Mezey and al, Science, 290,1179, 2000). In neurological disorders, such as Alzheimer's and Parkinson's diseases, auto-transplantation of neural cell types derived from mesenchymal stem cells offers the potential of replacing lost cells and recovering lost functions. Nestin is an intermediate filament protein predominantly expressed by neural stem cells and is used to identify neural progenitor. In this study, we demonstrate that cultured rat mesenchymal stem cells (rMSC) can express nestin in appropriate conditions. Two factors contribute to the regulation of nestin expression by rMSC : 1) the presence of serum-derived components in the culture medium which repress nestin expression and 2) the cell’s number of passages. LPA and thrombin mimic this serum effect. Furthermore, when nestin- positive cells are trypsinized and resuspended into culture conditions used for neural stem cells (NSC), sphere formation is observed. Likewise, by co-cultivating nestin-positive rMSC with NSC derived from green mouse, heterogenous spheres were obtained. When those heterogenous spheres are placed on polyornithine-coated surfaces, a differentiation of some rMSC into GFAP-positive cells occurs. These results indicate that nestin expression might be a pre-requisite for the acquisition by rMSC of the capacity to differentiate into some neural cell types. [less ▲]

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See detailFunctional glycine receptors are expressed by postnatal nestin-positive neural stem/progenitor cells
Nguyen, Laurent ULg; Malgrange, Brigitte ULg; Belachew, Shibeshih ULg et al

in European Journal of Neuroscience (2002), 15(8), 1299-1305

Multipotent neural stem and progenitor cells (NS/PCs) are well-established cell subpopulations occurring in the developing, and also in the mature mammalian nervous systems. Trophic and transcription ... [more ▼]

Multipotent neural stem and progenitor cells (NS/PCs) are well-established cell subpopulations occurring in the developing, and also in the mature mammalian nervous systems. Trophic and transcription factors are currently the main signals known to influence the development and the commitment of NS/PCs and their progeny. However, recent studies suggest that neurotransmitters could also contribute to neural development. In that respect, rodent-cultured embryonic NS/PCs have been reported to express functional neurotransmitter receptors. No similar investigation has, however, been made in postnatal and/or in adult rodent brain stem cells. In this study, using RT-PCR and immunocytochemical methods, we show that alpha(1) -, alpha(2) - and beta-subunit mRNAs and alpha-subunit proteins of the glycine ionotropic receptor are expressed by 80.5 +/- 0.9% of postnatal rat striatum-derived, nestin-positive cells within cultured neurospheres. Whole-cell patch-clamp experiments further demonstrated that glycine triggers in 33.5% of these cells currents that can be reversibly blocked by strychnine and picrotoxin. This demonstrates that NS/PCs express functional glycine receptors, the consequence(s) of their activation remaining unknown. [less ▲]

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See detailProliferative generation of mammalian auditory hair cells in culture
Malgrange, Brigitte ULg; Belachew, Shibeshih ULg; Thiry, Marc ULg et al

in Mechanisms of Development (2002), 112(1-2), 79-88

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See detailProliferation generation of auditory hair cells in culture
Malgrange, B; Belachew, S; Thiry, Marc ULg et al

in Acta Oto-Rhino-Laryngologica Belgica (2002), 56

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See detailPharmacologic treatment of inner ear: from basic science to the patient.
Lefèbvre, Philippe ULg; Staecker, H.; Van de Water, T. et al

in Acta Oto-Rhino-Laryngologica Belgica (2002), 56(1), 45-9

Most of the deafness are of sensorineural origin and are characterized by a loss of hair cells and of spiral ganglion neurons. At the present time, hearing aids are the only treatment. However, in some ... [more ▼]

Most of the deafness are of sensorineural origin and are characterized by a loss of hair cells and of spiral ganglion neurons. At the present time, hearing aids are the only treatment. However, in some diseases of the inner ear, pharmacological treatment have been proposed and used successfully. In this paper, we will review some basic science aspects of the biology of the neurosensory structures of the inner ear, in particular of the auditory neurons, that lead to the rationale of some treatments for the inner ear diseases. Developmental studies, neuronal cell culture experiments, and analyses of gene knockout animals reveal a number of growth factors which are important for the rescue and repair of injured auditory neurons in the inner ear. These factors rescue the injured auditory neurons in vivo. Furthermore, perfusion of antioxydant to the cochlea prevented the hearing loss induced by cisplatin. These in vitro and in vivo experiments demonstrate that it is possible to manipulate the neurosensory structures of the inner ear and provide an effective treatment to prevent the degeneration of the neurons. The molecules or drugs can be administered locally to the inner ear through a direct perilymphatic perfusion or through the round window membrane. As an example, we will discuss the treatment of patients suffering from idiopathic sensorineural hearing loss which can be treated successfully by a perfusion through the round window membrane, improving their hearing threshold and their speech discrimination. [less ▲]

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See detailMechanisms of cell death in the injured auditory system: Otoprotective strategies
Lefèbvre, Philippe ULg; Malgrange, Brigitte ULg; Lallemend, François et al

in Audiology & Neuro-otology (2002), 7(3, May-Jun), 165-170

Oxidative stress insults such as neurotrophin withdrawal, sound trauma, hypoxia/ischemia, ototoxic antibiotics, and chemotherapeutic agents have been shown to induce apoptosis of both auditory hair cells ... [more ▼]

Oxidative stress insults such as neurotrophin withdrawal, sound trauma, hypoxia/ischemia, ototoxic antibiotics, and chemotherapeutic agents have been shown to induce apoptosis of both auditory hair cells and neurons. In this paper, we review some components of the apoptotic pathways leading to the death of hair cells and auditory induced by growth factor withdrawal or cisplatin intoxication: (1) reactive oxygen species and free radicals are formed as by-products of several metabolic pathways and these molecules can themselves cause cell damage by reacting with cellular proteins; (2) activation of caspases, and (3) activation of calpain. These mechanisms have several different points at which inhibitors could be targeted to protect cells from programmed cell death, including the prevention of oxidative stress-induced apoptosis and the activation of caspases and calpains. Copyright (C) 2002 S. Karger AG, Basel. [less ▲]

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See detailEffects of incidental and intentional feature binding on recognition: a behavioural and PET activation study
Lekeu, Françoise ULg; Van der Linden, Martial ULg; Collette, Fabienne ULg et al

in Neuropsychologia (2002), 40(2), 131-144

Using Positron Emission Tomography (PET), we investigated cerebral regions associated with the episodic recognition of words alone and words bound to contextual colours. Two modes of colour encoding were ... [more ▼]

Using Positron Emission Tomography (PET), we investigated cerebral regions associated with the episodic recognition of words alone and words bound to contextual colours. Two modes of colour encoding were tested: incidental and intentional word-to-colour binding. Word-only recognition was associated with brain activation in a lexico-semantic left middle temporal region and in the cerebellum following an incidental colour encoding, and with brain activation in the left posterior middle frontal gyrus, right anterior cingulate and right inferior frontal gyrus following an intentional encoding. Recognition of bound features was associated with activation in left prefrontal and superior parietal regions following an incidental colour encoding, and with preferential right prefrontal cortex activation following an intentional colour encoding. Our results are in line with the hypothesis of a parietal involvement in context processing, and prefrontal areas in monitoring retrieval processes. Our results also support the hypothesis of a 'cortical asymmetry for reflective activity' (CARA). [less ▲]

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