References of "Moonen, Gustave"
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See detailActivation of protein kinase CbetaI constitutes a new neurotrophic pathway for deafferented spiral ganglion neurons
Lallemend, François; Hadjab, Saida; Hans, Grégory ULg et al

in Journal of Cell Science (2005), 118(19), 4511-4525

In mammals, degeneration of peripheral auditory neurons constitutes one of the main causes of sensorineural hearing loss. Unfortunately, to date, pharmacological interventions aimed at counteracting this ... [more ▼]

In mammals, degeneration of peripheral auditory neurons constitutes one of the main causes of sensorineural hearing loss. Unfortunately, to date, pharmacological interventions aimed at counteracting this condition have not presented complete effectiveness in protecting the integrity of cochlear neural elements. In this context, the protein kinase C (PKC) family of enzymes are important signalling molecules that play a role in preventing neurodegeneration after nervous system injury. The present study demonstrates, for the first time, that the PKC signalling pathway is directly neurotrophic to axotomised spiral ganglion neurons (SGNs). We found that PKC beta I was strictly expressed by postnatal and adult SGNs both in situ and in vitro. In cultures of SGNs, we observed that activators of PKC, such as phorbol esters and bryostatin 1, induced neuronal survival and neurite regrowth in a manner dependent on the activation of PKC beta I. The neuroprotective effects of PKC activators were suppressed by pre-treatment with LY294002 (a PI3K inhibitor) and with U0126 (a MEK inhibitor), indicating that PKC activators promote the survival and neurite outgrowth of SGNs by both PI3K/Akt and MEK/ERK-dependent mechanisms. In addition, whereas combining the neurotrophins brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) was shown to provide only an additive effect on SGN survival, the interaction between PKC and neurotrophin signalling gave rise to a synergistic increase in SGN survival. Taken together, the data indicate that PKC beta I activation represents a key factor for the protection of the integrity of neural elements in the cochlea. [less ▲]

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See detailDevelopmental regulation of beta-carboline-induced inhibition of glycine-evoked responses depends on glycine receptor beta subunit expression
Mangin, Jean-Marie; Nguyen, Laurent ULg; Gougnard, Catherine et al

in Molecular Pharmacology (2005), 67(5), 1783-1796

In this work, we show that beta-carbolines, which are known negative allosteric modulators of GABA A receptors, inhibit glycine-induced currents of embryonic mouse spinal cord and hippocampal neurons. In ... [more ▼]

In this work, we show that beta-carbolines, which are known negative allosteric modulators of GABA A receptors, inhibit glycine-induced currents of embryonic mouse spinal cord and hippocampal neurons. In both cell types, beta-carboline-induced inhibition of glycine receptor (GlyR)-mediated responses decreases with time in culture. Single-channel recordings show that the major conductance levels of GlyR unitary currents shifts from high levels (>= 50 pS) in 2 to 3 days in vitro (DIV) neurons to low levels (< 50 pS) in 11 to 14 DIV neurons, assessing the replacement of functional homomeric GlyR by heteromeric GlyR. In cultured spinal cord neurons, the disappearance of beta-carboline inhibition of glycine responses and high conductance levels is almost complete in mature neurons, whereas a weaker decrease in beta-carboline-evoked glycine response inhibition and high conductance level proportion is observed in hippocampal neurons. To confirm the hypothesis that the decreased sensitivity of GlyR to beta-carbolines depends on beta subunit expression, Chinese hamster ovary cells were permanently transfected either with GlyR alpha 2 subunit alone or in combination with GlyR beta subunit. Single-channel recordings revealed that the major conductance levels shifted from high levels (>= 50 pS) in GlyR-alpha 2-transfected cells to low levels (< 50 pS) in GlyR-alpha 2-containing cells. Consistently, both picrotoxinand beta-carboline-induced inhibition of glycine-gated currents were significantly decreased in GlyR-alpha 2-transfected cells compared with GlyR-alpha 2-containing cells. In summary, we demonstrate that the incorporation of beta subunits in GlyRs confers resistance not only to picrotoxin but also to beta-carbolineinduced inhibition. Furthermore, we also provide evidence that hippocampal neurons undergo in vitro a partial maturation process of their GlyR-mediated responses. [less ▲]

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See detailPeripheral benzodiazepine receptor (PBR) ligand cytotoxicity unrelated to PBR expression
Hans, Grégory ULg; Wislet, Sabine ULg; Lallemend, François et al

in Biochemical Pharmacology (2005), 69(5), 819-830

Some synthetic ligands of the peripheral-type benzodiazepine receptor (PBR), an 18 kDa protein of the outer mitochondrial membrane, are cytotoxic for several tumor cell lines and arise as promising ... [more ▼]

Some synthetic ligands of the peripheral-type benzodiazepine receptor (PBR), an 18 kDa protein of the outer mitochondrial membrane, are cytotoxic for several tumor cell lines and arise as promising chemotherapeutic candidates. However, conflicting results were reported regarding the actual effect of these drugs on cellular survival ranging from protection to toxicity. Moreover, the concentrations needed to observe such a toxicity were usually high, far above the affinity range for their receptor, hence questioning its specificity. In the present study, we have shown that micromolar concentrations of FGIN-1-27 And Ro 5-4864, two chemically unrelated PBR ligands are toxic for both PBR-expressing SK-N-BE neuroblastoma cells and PBR-deficient Jurkat lymphoma cells. We have thereby demonstrated that the cytotoxicity of these drugs is unrelated to their PBR-binding activity. Moreover, Ro 54864-induced cell death differed strikingly between both cell types, being apoptotic in Jurkat cells while necrotic in SK-N-BE cells. Again, this did not seem to be related to PBR expression since Ro 5-4864-induced death of PBR-transfected Jurkat cells remained apoptotic. Taken together, our results show that PBR is unlikely to mediate all the effects of these PBR ligands. They however confirm that some of these ligands are very effective cytotoxic drugs towards various cancer cells, even for reputed chemoresistant tumors such as neuroblastoma, and, surprisingly, also for PBR-lacking tumor cells. (C) 2004 Elsevier Inc. All rights reserved. [less ▲]

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See detailDiffuse cortical atrophy in a patient with Turner syndrome and Leber hereditary optic neuropathy
Blaise, Pierre ULg; Fumal, Arnaud ULg; Janin, Nicolas ULg et al

in Journal of Neurology (2005), 252(2), 232-233

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See detailbeta-carbolines induce apoptosis in cultured cerebellar granule neurons via the mitochondrial pathway
Hans, Grégory ULg; Malgrange, Brigitte ULg; Lallemend, François et al

in Neuropharmacology (2005), 48(1), 105-117

N-Butyl-beta-carboline-3-carboxylate (betaCCB) is, together with 2-methyl-norharmanium and 2,9-dimethylnorharmanium ions, an endogenously occurring beta-carboline. Due to their structural similarities ... [more ▼]

N-Butyl-beta-carboline-3-carboxylate (betaCCB) is, together with 2-methyl-norharmanium and 2,9-dimethylnorharmanium ions, an endogenously occurring beta-carboline. Due to their structural similarities with the synthetic neurotoxin 1-methy14-phenyl-1,2,3,6-tetrahydropyridine (MPTP), harman and norharman compounds have been proposed to be involved in the pathogenesis of Parkinson's disease. While also structurally related, betaCCB has received much less interest in that respect although we had previously demonstrated that it induces the apoptotic cell death of cultured cerebellar granule neurons (CGNs). Herein, we have investigated the molecular events leading to CGN apoptosis upon betaCCB treatment. We first demonstrated that betaCCB-induced apoptosis occurs in neurons only, most likely as a consequence of a specific neuronal uptake as shown using binding/uptake experiments. Then we observed that, in betaCCB-treated CGNs, caspases 9, 3 and 8 were successively activated, suegesing an activation of the mitochondrial pathway. Consistently, betaCCB also induced the release from the mitochondrial intermembrane space of two pro-apoptotic factors. i.e. cytochrome c and apotptosis inducing factor (AIF). Interestingly, no mitochondrial membrane depolarisation was associated with this release. suggesting a mitochondrial permeability transition pore-independent mechanism. The absence of any neuroprotective effect provided by two mPTP inhibitors. i.e. cyclosporine A and bongkrekic acid. further supported this hypothesis. Together. these results show that betaCCB is specifically taken up by neuronal cells where it triggers a specific permeabilization of the outer mitochondrial membrane and a subsequent apoptotic cell death. (C) 2004 Elsevier Ltd. All rights reserved. [less ▲]

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See detailMolecular pathways involved in apoptotic cell death in the injured cochlea: Cues to novel therapeutic strategies
Lallemend, François; Lefèbvre, Philippe ULg; Hans, Grégory ULg et al

in Current Pharmaceutical Design (2005), 11(17), 2257-2275

Most hearing loss results from lesions of the sensory cells and/or neurons of the auditory portion of the inner ear. To date, only the cochlear implantation offers long-term hearing-aid benefit, but still ... [more ▼]

Most hearing loss results from lesions of the sensory cells and/or neurons of the auditory portion of the inner ear. To date, only the cochlear implantation offers long-term hearing-aid benefit, but still with limited performance and expensive cost. While the underlying causes of deafness are not clear, the death or hair cells and/or neurons and the loss of neuronal contacts are key pathological features. Pinpointing molecular events that control cell death in the cochlea is critical for the development of new strategies to prevent and treat deafness, whether in combination or not with cochlear implant therapy. [less ▲]

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See detailNeural mechanisms involved in the detection of our first name : A combined ERPs and PET study
Perrin, Fabien; Maquet, Pierre ULg; Peigneux, Philippe ULg et al

in Neuropsychologia (2005), 43(1), 12-19

In everyday social interactions, hearing our own first name captures our attention and gives rise to a sense of self-awareness, since it is one of the most socially self related stimulus. In the present ... [more ▼]

In everyday social interactions, hearing our own first name captures our attention and gives rise to a sense of self-awareness, since it is one of the most socially self related stimulus. In the present study, we combined ERPs and PET scan methods to explore the cerebral mechanisms underlying the detection of our own name. While categorical analyses of PET data failed to reveal significant results, we found that the amplitude of the P3 component, elicited when hearing one's own name, correlates with regional cerebral blood changes in right superior temporal sulcus, precuneus and medial prefrontal cortex. Additionally, the latter was more correlated to the P3 obtained for the subject's name compared to that obtained for other first names. These results suggest that the medial prefrontal cortex plays the most prominent role in self-processing. (C) 2004 Elsevier Ltd. All rights reserved. [less ▲]

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See detailCerebral processing of auditory and noxious stimuli in severely brain injured patients: Differences between VS and MCS
Boly, Mélanie ULg; Faymonville, Marie-Elisabeth ULg; Peigneux, Philippe ULg et al

in Neuropsychological Rehabilitation (2005), 15(3-4, Jul-Sep), 283-289

We review cerebral processing of auditory and noxious stimuli in minimally conscious state (MCS) and vegetative state (VS) patients. In contrast with limited brain activation found in VS patients, MCS ... [more ▼]

We review cerebral processing of auditory and noxious stimuli in minimally conscious state (MCS) and vegetative state (VS) patients. In contrast with limited brain activation found in VS patients, MCS patients show activation similar to controls in response to auditory, emotional and noxious stimuli. Despite an apparent clinical similarity between MCS and VS patients, functional imaging data show striking differences in cortical segregation and integration between these two conditions. However, in the absence of a generally accepted neural correlate of consciousness as measured by functional neuroirnaging, clinical assessment remains the gold standard for the evaluation and management of severely brain damaged patients. [less ▲]

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See detailPlasticity of cultured mesenchymal stem cells: switch from nestin-positive to excitable neuron-like phenotype.
Wislet-Gendebien, Sabine ULg; Hans, Grégory ULg; Leprince, Pierre ULg et al

in Stem Cells (2005), 23(3), 392-402

Bone marrow mesenchymal stem cells (MSCs) can differentiate into several types of mesenchymal cells, including osteocytes, chondrocytes, and adipocytes, but, under appropriate experimental conditions, can ... [more ▼]

Bone marrow mesenchymal stem cells (MSCs) can differentiate into several types of mesenchymal cells, including osteocytes, chondrocytes, and adipocytes, but, under appropriate experimental conditions, can also differentiate into nonmesenchymal cells--for instance, neural cells. These observations have raised interest in the possible use of MSCs in cell therapy strategies for various neurological disorders. In the study reported here, we addressed the question of in vitro differentiation of MSCs into functional neurons. First, we demonstrate that when they are co-cultured with cerebellar granule neurons, adult MSCs can express neuronal markers. Two factors are needed for the emergence of neuronal differentiation of the MSCs: the first one is nestin expression by MSCs (nestin is a marker for the responsive character of MSCs to extrinsic signals), and the second one is a direct cell-cell interaction between neural cells and MSCs that allows the integration of these extrinsic signals. Three different approaches suggest that neural phenotypes arise from MSCs by a differentiation rather than a cell fusion process, although this last phenomenon can also coexist. The expression of several genes--including sox, pax, notch, delta, frizzled, and erbB--was analyzed by quantitative reverse transcription polymerase chain reaction (RT-PCR) in order to further characterize the nestin-positive phenotype compared to the nestin-negative one. An overexpression of sox2, sox10, pax6, fzd, erbB2, and erbB4 is found in nestin-positive MSCs. Finally, electrophysiological analyses demonstrate that MSC-derived neuron-like cells can fire single-action potentials and respond to several neurotransmitters such as GABA, glycine, and glutamate. We conclude that nestin-positive MSCs can differentiate in vitro into excitable neuron-like cells. [less ▲]

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See detailThe locked-in syndrome : what is it like to be conscious but paralyzed and voiceless?
Laureys, Steven ULg; Pellas, Frédéric; Van Eeckhout, Philippe et al

in Progress in Brain Research (2005), 150(Boundaries of Consciousness: Neurobiology and Neuropathology), 495-511

The locked-in syndrome (pseudocoma) describes patients who are awake and conscious but selectively deefferented, i.e., have no means of producing speech, limb or facial movements. Acute ventral pontine ... [more ▼]

The locked-in syndrome (pseudocoma) describes patients who are awake and conscious but selectively deefferented, i.e., have no means of producing speech, limb or facial movements. Acute ventral pontine lesions are its most common cause. People with such brainstem lesions often remain comatose for some days or weeks, needing artificial respiration and then gradually wake up, but remaining paralyzed and voiceless, superficially resembling patients in a vegetative state or akinetic mutism, In acute locked-in syndrome (LIS), eye-coded communication and evaluation of cognitive and emotional functioning is very limited because vigilance is fluctuating and eye movements may be inconsistent, very small, and easily exhausted. It has been shown that more than half of the time it is the family and not the physician who first realized that the patient was aware. Distressingly, recent studies reported that the diagnosis of LIS on average takes over 2.5 months. In some cases it took 4-6 years before aware and sensitive patients, locked in an immobile body, were recognized as being conscious. Once a LIS patient becomes medically stable, and given appropriate medical care, life expectancy increases to several decades. Even if the chances of good motor recovery are very limited, existing eye-controlled, computer-based communication technology currently allow the patient to control his environment, use a word processor coupled to a speech synthesizer, and access the worldwide net. Healthy individuals and medical professionals sometimes assume that the quality of life of an LIS patient is so poor that it is not worth living. On the contrary, chronic LIS patients typically self-report meaningful quality of life and their demand for euthanasia is surprisingly infrequent. Biased clinicians might provide less aggressive medical treatment and influence the family in inappropriate ways. It is important to stress that only the medically stabilized, informed LIS patient is competent to consent to or refuse life-sustaining treatment. Patients suffering from LIS should not be denied the right tot die - and to die with dignity - but also, and more importantly, and pain and symptom management. In our opinion, there is an urgent need for a renewed ethical and medicolegal framework for our care of locked-in patients. [less ▲]

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See detailZerebrale Funktionen bei hirngeschädigten Patienten. Was bedeuten Koma, "vegetative state“, "minimally conscious state“, "Locked-in-Syndrom“ und Hirntod?
Faymonville, Marie-Elisabeth ULg; Pantke, Karl-Heinz; Berré, Jacques et al

in Anaesthesist (2004), 53(12), 1195-1202

Comatose, vegetative, minimally conscious or locked-in patients represent a problem in terms of diagnosis, prognosis, treatment and everyday management at the intensive care unit. The evaluation of ... [more ▼]

Comatose, vegetative, minimally conscious or locked-in patients represent a problem in terms of diagnosis, prognosis, treatment and everyday management at the intensive care unit. The evaluation of possible cognitive functions in these patients is difficult because voluntary movements may be very small, inconsistent and easily exhausted. Functional neuroimaging cannot replace the clinical assessment of patients with altered states of consciousness. Nevertheless, it can describe objectively how deviant from normal the cerebral activity is and its regional distribution at rest and under various conditions of stimulation. The quantification of brain activity differentiates patients who sometimes only differ by a brief and incomplete blink of an eye. In the present paper, we will first try to define consciousness as it can be assessed at the patient's bedside. We then review the major clinical entities of altered states of consciousness encountered in the intensive care unit. Finally, we discuss the functional neuroanatomy of these conditions as assessed by positron emission tomography (PET) scanning. [less ▲]

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See detailCerebral processing in the minimally conscious state
Laureys, Steven ULg; Perrin, Fabien; Faymonville, Marie ULg et al

in Neurology (2004), 63(5), 916-918

We studied a patient in a minimally conscious state using PET and cognitive evoked potentials. Cerebral metabolism was below half of normal values. Auditory stimuli with emotional valence ( infant cries ... [more ▼]

We studied a patient in a minimally conscious state using PET and cognitive evoked potentials. Cerebral metabolism was below half of normal values. Auditory stimuli with emotional valence ( infant cries and the patient's own name) induced a much more widespread activation than did meaningless noise; the activation pattern was comparable with that previously obtained in controls. Cognitive potentials showed preserved P300 responses to the patient's own name. [less ▲]

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See detailStriatal PSA-NCAM(+) precursor cells from the newborn rat express functional glycine receptors
Nguyen, Laurent ULg; Malgrange, Brigitte ULg; Breuskin, Ingrid ULg et al

in Neuroreport (2004), 15(4), 583-587

Immunocytochemical analysis showed that ionotropic glycine receptors are expressed in neurogenic progenitors purified from the newborn rat striatum and expressing the polysialylated form of the neural ... [more ▼]

Immunocytochemical analysis showed that ionotropic glycine receptors are expressed in neurogenic progenitors purified from the newborn rat striatum and expressing the polysialylated form of the neural cell adhesion molecule, both in vitro and in situ. To ascertain whether glycine receptors were functional in vitro, whole-cell patch-clamp recordings demonstrated that glycine triggers inward strychnine-sensitive currents in the majority of these cells. Moreover, we found that glycine receptors expressed by these neurogenic progenitors display intermediate electrophysiological characteristics between those of glycine receptors expressed by neural stem cells and by mature interneurons from the rat striatum. Altogether, the present data show that functional strychnine-sensitive glycine receptors are expressed in neurogenic progenitors purified from the newborn rat striatum. [less ▲]

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See detailImaging a cognitive model of apraxia: The neural substrate of gesture-specific cognitive processes
Peigneux, Philippe ULg; Van der Linden, Martial ULg; Garraux, Gaëtan ULg et al

in Human Brain Mapping (2004), 21(3), 119-142

The present study aimed to ascertain the neuroanatomical basis of an influential neuropsychological model for upper limb apraxia [Rothi LJ, et al. The Neuropsychology of Action. 1997. Hove, UK: Psychology ... [more ▼]

The present study aimed to ascertain the neuroanatomical basis of an influential neuropsychological model for upper limb apraxia [Rothi LJ, et al. The Neuropsychology of Action. 1997. Hove, UK: Psychology Press]. Regional cerebral blood flow was measured in healthy volunteers using (H2O)-O-15 PET during performance of four tasks commonly used for testing upper limb apraxia, i.e., pantomime of familiar gestures on verbal command, imitation of familiar gestures, imitation of novel gestures, and an action-semantic task that consisted in matching objects for functional use. We also re-analysed data from a previous PET study in which we investigated the neural basis. of the visual analysis of gestures. First; we found that two sets of discrete brain areas are predominantly engaged in the imitation of familiar and novel gestures, respectively. Segregated brain activation for novel gesture mutation concur with neuropsychological reports to support the hypothesis that knowledge about the organization of the human body mediates the transition from visual perception to motor execution when imitating novel gestures [Goldenberg Neuropsychologia 1995;35.63-72]. Second, conjunction analyses revealed distinctive neural bases for most of the gesture-specific cognitive processes proposed in this cognitive model of upper limb apraxia. However, a functional analysis of brain imaging data suggested that one single memory store may be used for "to be-perceived" and "to-be-produced" gestural representations, departing from Rothi et al.'s proposal. Based on the above considerations, we suggest and discuss a revised model for upper limb apraxia that might best account for both brain imaging findings and neuropsychological dissociations reported in the apraxia literature. (C) 2004 Wiley-Liss, Inc. [less ▲]

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See detailBrain function in the vegetative state
Laureys, Steven ULg; Faymonville, Marie-Elisabeth ULg; De Tiège, Xavier et al

in Brain Death and Disorders of Consciousness (2004)

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See detailAuditory processing in severely brain injured patients: differences between the minimally conscious state and the persistent vegetative state.
Boly, Mélanie ULg; FAYMONVILLE, Marie-Elisabeth ULg; Peigneux, Philippe ULg et al

in Archives of Neurology (2004), 61(2), 233-8

BACKGROUND: The minimally conscious state (MCS) is a recently defined clinical condition; it differs from the persistent vegetative state (PVS) by the presence of inconsistent, but clearly discernible ... [more ▼]

BACKGROUND: The minimally conscious state (MCS) is a recently defined clinical condition; it differs from the persistent vegetative state (PVS) by the presence of inconsistent, but clearly discernible, behavioral evidence of consciousness. OBJECTIVE: To study auditory processing among patients who are in an MCS, patients who are in a PVS, and healthy control subjects. METHODS: By means of (15)O-radiolabeled water-positron emission tomography, we measured changes in regional cerebral blood flow induced by auditory click stimuli in 5 patients in an MCS, 15 patients in a PVS, and 18 healthy controls. RESULTS: In both patients in an MCS and the healthy controls, auditory stimulation activated bilateral superior temporal gyri (Brodmann areas 41, 42, and 22). In patients in a PVS, the activation was restricted to Brodmann areas 41 and 42 bilaterally. We also showed that, compared with patients in a PVS, patients in an MCS demonstrated a stronger functional connectivity between the secondary auditory cortex and temporal and prefrontal association cortices. CONCLUSIONS: Although assumptions about the level of consciousness in severely brain injured patients are difficult to make, our findings suggest that the cerebral activity observed in patients in an MCS is more likely to lead to higher-order integrative processes, thought to be necessary for the gain of conscious auditory perception. [less ▲]

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See detailNestin-positive mesenchymal stem cells favour the astroglial lineage in neural progenitors and stem cells by releasing active BMP4.
Wislet-Gendebien, Sabine ULg; Bruyere, Françoise ULg; Hans, Grégory ULg et al

in BMC Neuroscience (2004), 5

BACKGROUND: Spontaneous repair is limited after CNS injury or degeneration because neurogenesis and axonal regrowth rarely occur in the adult brain. As a result, cell transplantation has raised much ... [more ▼]

BACKGROUND: Spontaneous repair is limited after CNS injury or degeneration because neurogenesis and axonal regrowth rarely occur in the adult brain. As a result, cell transplantation has raised much interest as potential treatment for patients with CNS lesions. Several types of cells have been considered as candidates for such cell transplantation and replacement therapies. Foetal brain tissue has already been shown to have significant effects in patients with Parkinson's disease. Clinical use of the foetal brain tissue is, however, limited by ethical and technical problems as it requires high numbers of grafted foetal cells and immunosuppression. Alternatively, several reports suggested that mesenchymal stem cells, isolated from adult bone marrow, are multipotent cells and could be used in autograft approach for replacement therapies. RESULTS: In this study, we addressed the question of the possible influence of mesenchymal stem cells on neural stem cell fate. We have previously reported that adult rat mesenchymal stem cells are able to express nestin in defined culture conditions (in the absence of serum and after 25 cell population doublings) and we report here that nestin-positive (but not nestin-negative) mesenchymal stem cells are able to favour the astroglial lineage in neural progenitors and stem cells cultivated from embryonic striatum. The increase of the number of GFAP-positive cells is associated with a significant decrease of the number of Tuj1- and O4-positive cells. Using quantitative RT-PCR, we demonstrate that mesenchymal stem cells express LIF, CNTF, BMP2 and BMP4 mRNAs, four cytokines known to play a role in astroglial fate decision. In this model, BMP4 is responsible for the astroglial stimulation and oligodendroglial inhibition, as 1) this cytokine is present in a biologically-active form only in nestin-positive mesenchymal stem cells conditioned medium and 2) anti-BMP4 antibodies inhibit the nestin-positive mesenchymal stem cells conditioned medium inducing effect on astrogliogenesis. CONCLUSIONS: When thinking carefully about mesenchymal stem cells as candidates for cellular therapy in neurological diseases, their effects on resident neural cell fate have to be considered. [less ▲]

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See detailResidual cerebral functioning in the vegetative state
Laureys, Steven ULg; Faymonville, Marie-Elisabeth ULg; De Tiège, X. et al

in Arco di Giano (2004)

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See detailThe Inhibition of Cyclin-Dependent Kinases Induces Differentiation of Supernumerary Hair Cells and Deiters' Cells in the Developing Organ of Corti
Malgrange, Brigitte ULg; Knockaert, Marie; Belachew, Shibeshih ULg et al

in FASEB Journal (2003), 17(14), 2136-8

In the embryonic day 19 organs of Corti, we showed that roscovitine, a chemical inhibitor of cyclin-dependent kinases (CDKs), significantly increased the number of hair cells (HCs) and corresponding ... [more ▼]

In the embryonic day 19 organs of Corti, we showed that roscovitine, a chemical inhibitor of cyclin-dependent kinases (CDKs), significantly increased the number of hair cells (HCs) and corresponding supporting cells (SCs) by triggering differentiation of precursor cells without interacting with cell proliferation. The effect of roscovitine was mimicked by other CDK1, 2, 5, and 7 inhibitors but not by CDK4/6 and mitogen-activated protein kinase pathway antagonists. Immunohistochemical analysis indicated that roscovitine-specific intracellular targets, CDK1, 2, 5, and 7, were expressed in the organ of Corti and especially in Hensen's cells. Affinity chromatography studies showed a tight correlation between the protein levels of CDK1/2 and 5 and the rate of roscovitine-induced supernumerary cells in the organ of Corti. In addition, we demonstrated that basal CDK activity was higher and more roscovitine-sensitive at developmental stages that are selectively permissive for the emergence of supernumerary cells. These results suggest that CDKs are involved in the normal development of the organ of Corti and that, at least in E19 embryos, inhibition of CDKs is sufficient to trigger the differentiation of HCs and corresponding SCs, presumably from the Hensen's cell progenitors and/or from progenitors located in the greater epithelial ridge area. [less ▲]

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See detailSubstance P protects spiral ganglion neurons from apoptosis via PKC-Ca2+-MAPK/ERK pathways
Lallemend, François; Lefèbvre, Philippe ULg; Hans, Grégory ULg et al

in Journal of Neurochemistry (2003), 87(2), 508-521

In the current study, we have investigated the ability of substance P (SP) to protect 3-day-old (P3) rat spiral ganglion neurons (SGNs) from trophic factor deprivation (TFD)-induced cell death. The ... [more ▼]

In the current study, we have investigated the ability of substance P (SP) to protect 3-day-old (P3) rat spiral ganglion neurons (SGNs) from trophic factor deprivation (TFD)-induced cell death. The presence of SP high affinity neurokinin-1 receptor (NK1) transcripts was detected in the spiral ganglion and the NK1 protein localized to SGNs both ex vivo and in vitro. Treatment with SP increased cytoplasmic Ca2+ in SGNs, further arguing for the presence of functional NK1 on these neurons. Both SP and the agonist [Sar(9), Met(O-2)(11)]-SP significantly decreased SGN cell death induced by TFD, with no effect on neurite outgrowth. The survival promoting effect of SP was blocked by the NK1 antagonist, WIN51708. Both pan-caspase inhibitor BOC-D-FMK and SP treatments markedly reduced activation of caspases and DNA fragmentation in trophic factor deprived-neurons. The neuroprotective action of SP was antagonised by specific inhibitors of second messengers, including 1.2-bis-(O-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid (BAPTA-AM) to chelate cytosolic Ca2+, the protein kinase C (PKC) inhibitors bisindolylmaleimide I, Go6976 and LY333531 and the MAPK/ERK inhibitor U0126. In contrast, nifedipine, a specific inhibitor of L-type Ca2+ channel, and LY294002, a phosphatidylinositol-3-OH kinase (PI3K) inhibitor, had no effect on SP trophic support of SGNs. Moreover, activation of endogenous PKC by 4beta-phorbol 12-myristate 13-acetate (PMA) also reduced the loss of trophic factor-deprived SGNs. Thus, NK1 expressed by SGNs transmit a survival-promoting regulatory signal during TFD-induced SGN cell death via pathways involving PKC activation, Ca2+ signalling and MAPK/ERK activation, which can be accounted for by an inhibition of caspase activation. [less ▲]

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