References of "BELACHEW, Shibeshih"
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See detailThe timed 100-meter walk test: an easy-t-use, sensitive tool to detect and evaluate restricted walking capacities in multiple sclerosis.
Belachew, Shibeshih ULg; CALAY, Philippe ULg; DELVAUX, Valérie ULg et al

Conference (2009, June)

Objectives: The primary aim of this study was to develop a quantitative ambulation test that correlates with the maximal walking distance in multiple sclerosis (MS) patients. Background: The timed 25-foot ... [more ▼]

Objectives: The primary aim of this study was to develop a quantitative ambulation test that correlates with the maximal walking distance in multiple sclerosis (MS) patients. Background: The timed 25-foot walk (T25FW) weakly correlates with overall walking capacities of MS patients. We developed the timed 100-meter walk test (T100T), which besides reflecting speed may be more sensitive to other walking parameters such as gait and spasticity-related fatigue. Methods: In the T100T, the patient is instructed to walk as fast as possible on a distance of 100 meters. Eighty-eight MS patients with an EDSS score from 0 to 5.5 and 60 normal controls performed the T100T and the T25FW. In addition, 30 normal controls and 30 patients performed the tests twice. Results: T25FW (R2= 0.79) and T100T (R2 = 0.89) correlated with the nonlinear distribution of EDSS scores. The correlation between T100T and T25FW values was high (r2 = 0.81) for the low (0 to 3.0) and high (3.5-5.5) scores of EDSS. The intra-class correlations were excellent and similar for both tests. The range of T100T values in MS patients (40.4 to 114.7 seconds) was 10-fold wider than that of the T25FW (3.0 to 9.1 seconds). The univariate distribution analyses demonstrated that abnormal T100T values appear to be more sensitive than T25FW to predict walking limitations. Finally, the correlation with the reported and/or actual maximal walking distance without aid and rest was significantly better for T100T. Conclusions : The T100T proves to be superior to the T25FW in terms of discriminatory power for the detection and evaluation of restricted walking capacities in MS. The T100T should be of interest for clinical trials studying disability worsening and improvement across the spectrum of EDSS. It may provide more sensitive measure for ambulation change in quantifying progressive MS pathology. [less ▲]

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See detailElongator controls the migration and differentiation of cortical neurons through acetylation of a tubulin
Creppe, Catherine ULg; Malinouskaya, Lina ULg; Volvert, Marie-Laure ULg et al

in Cell (2009), 136

The generation of cortical projection neurons relies on the coordination of radial migration with branching. Here we report that the multi-subunit histone acetyltransferase Elongator complex, which ... [more ▼]

The generation of cortical projection neurons relies on the coordination of radial migration with branching. Here we report that the multi-subunit histone acetyltransferase Elongator complex, which contributes to transcript elongation, also regulates the maturation of projection neurons. Indeed, silencing of its scaffold (Elp1) or catalytic subunit (Elp3) cell-autonomously delays the migration and impairs the branching of projection neurons. Strikingly, neurons defective in Elongator show reduced levels of acetylated alpha tubulin. A direct reduction of alpha tubulin acetylation leads to comparable defects in cortical neurons and suggests that alpha tubulin is a target of Elp3. This is further supported by the demonstration that Elp3 promotes acetylation and counteracts HDAC6-mediated deacetylation of this substrate in vitro. Our results uncover alpha tubulin as a target of the Elongator complex and suggest that a tight regulation of its acetylation underlies the maturation of cortical projection neurons. [less ▲]

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See detailAdult neurogenesis and the diseased brain.
Vandenbosch, Renaud ULg; Borgs, Laurence ULg; Beukelaers, Pierre ULg et al

in Current Medicinal Chemistry (2009), 16(6), 652-66

For a long time it was believed that the adult mammalian brain was completely unable to regenerate after insults. However, recent advances in the field of stem cell biology, including the identification ... [more ▼]

For a long time it was believed that the adult mammalian brain was completely unable to regenerate after insults. However, recent advances in the field of stem cell biology, including the identification of adult neural stem cells (NSCs) and evidence regarding a continuous production of neurons throughout life in the dentate gyrus (DG) and the subventricular zone of the lateral ventricles (SVZ), have provided new hopes for the development of novel therapeutic strategies to induce regeneration in the damaged brain. Moreover, proofs have accumulated this last decade that endogenous stem/progenitor cells of the adult brain have an intrinsic capacity to respond to brain disorders. Here, we first briefly summarize our current knowledge related to adult neurogenesis before focusing on the behaviour of adult neural stem/progenitors cells following stroke and seizure, and describe some of the molecular cues involved in the response of these cells to injury. In the second part, we outline the consequences of three main neurodegenerative disorders on adult neurogenesis and we discuss the potential therapeutic implication of adult neural stem/progenitors cells during the course of these diseases. [less ▲]

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See detailCell "circadian" cycle: new role for mammalian core clock genes.
Borgs, Laurence ULg; Beukelaers, Pierre ULg; Vandenbosch, Renaud ULg et al

in Cell Cycle (Georgetown, Tex.) (2009), 8(6), 832-7

In mammals, 24 hours rhythms are organized as a biochemical network of molecular clocks that are operative in all tissues, with the master clock residing in the hypothalamic suprachiasmatic nucleus (SCN ... [more ▼]

In mammals, 24 hours rhythms are organized as a biochemical network of molecular clocks that are operative in all tissues, with the master clock residing in the hypothalamic suprachiasmatic nucleus (SCN). The core pacemakers of these clocks consist of auto-regulatory transcriptional/post-transcriptional feedback loops. Several lines of evidence suggest the existence of a crosstalk between molecules that are responsible for the generation of circadian rhythms and molecules that control the cell cycle progression. In addition, highly specialized cell cycle checkpoints involved in DNA repair after damage seem also, at least in part, mediated by clock proteins. Recent studies have also highlighted a putative connection between clock protein dysfunction and cancer progression. This review discusses the intimate relation that exists between cell cycle progression and components of the circadian machinery. [less ▲]

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See detailPeriod 2 regulates neural stem/progenitor cell proliferation in the adult hippocampus.
Borgs, Laurence ULg; Beukelaers, Pierre ULg; Vandenbosch, Renaud ULg et al

in BMC Neuroscience (2009), 10

BACKGROUND: Newborn granule neurons are generated from proliferating neural stem/progenitor cells and integrated into mature synaptic networks in the adult dentate gyrus of the hippocampus. Since light ... [more ▼]

BACKGROUND: Newborn granule neurons are generated from proliferating neural stem/progenitor cells and integrated into mature synaptic networks in the adult dentate gyrus of the hippocampus. Since light/dark variations of the mitotic index and DNA synthesis occur in many tissues, we wanted to unravel the role of the clock-controlled Period2 gene (mPer2) in timing cell cycle kinetics and neurogenesis in the adult DG. RESULTS: In contrast to the suprachiasmatic nucleus, we observed a non-rhythmic constitutive expression of mPER2 in the dentate gyrus. We provide evidence that mPER2 is expressed in proliferating neural stem/progenitor cells (NPCs) and persists in early post-mitotic and mature newborn neurons from the adult DG. In vitro and in vivo analysis of a mouse line mutant in the mPer2 gene (Per2Brdm1), revealed a higher density of dividing NPCs together with an increased number of immature newborn neurons populating the DG. However, we showed that the lack of mPer2 does not change the total amount of mature adult-generated hippocampal neurons, because of a compensatory increase in neuronal cell death. CONCLUSION: Taken together, these data demonstrated a functional link between the constitutive expression of mPER2 and the intrinsic control of neural stem/progenitor cells proliferation, cell death and neurogenesis in the dentate gyrus of adult mice. [less ▲]

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See detailSevere liver dysfunction in a patient with multiple sclerosis: the guilty party is not always the disease-modifying therapy
Hotermans, C.; Belachew, Shibeshih ULg; Moonen, Gustave ULg et al

in Multiple Sclerosis : Clinical & Laboratory Research (2009), 15(11), 1378-1379

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See detailLes anticorps monoclonaux en neurologie.
Jedidi, Zayd ULg; Jedidi, Haroun ULg; Moonen, Gustave ULg et al

in Revue Médicale de Liège (2009), 64(5-6), 305-9

Since their inception in the 1970's, monoclonal antibody therapies became increasingly efficient and common in numerous medical conditions and their use in neurology has been boosted during the last ... [more ▼]

Since their inception in the 1970's, monoclonal antibody therapies became increasingly efficient and common in numerous medical conditions and their use in neurology has been boosted during the last couple of years with the rise of natalizumab (Tysabri). Furthermore, if most monoclonal antibodies currently assessed in neurologic conditions remain considered as experimental, they may soon become first-line approved treatments in a broad range of neuromuscular and demyelinating diseases. Since the introduction of new therapies is likely to unravel specific adverse events and sui generis iatrogenic disorders, it is important to be able to recognize the side-effects of monoclonal antibodies delivered for neurological or non-neurological diseases. [less ▲]

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See detailStrategies to Regenerate Hair Cells: Identification of Progenitors and Critical Genes
Breuskin, Ingrid ULg; Bodson, Morgan ULg; Thelen, Nicolas ULg et al

in Hearing Research (2008), 236(1-2), 1-10

Deafness commonly results from a lesion of the sensory cells and/or of the neurons of the auditory part of the inner ear. There are currently no treatments designed to halt or reverse the progression of ... [more ▼]

Deafness commonly results from a lesion of the sensory cells and/or of the neurons of the auditory part of the inner ear. There are currently no treatments designed to halt or reverse the progression of hearing loss. A key goal in developing therapy for sensorineural deafness is the identification of strategies to replace lost hair cells. In amphibians and birds, a spontaneous post-injury regeneration of all inner ear sensory hair cells occurs. In contrast, in the mammalian cochlea, hair cells are only produced during embryogenesis. Many studies have been carried out in order to demonstrate the persistence of endogenous progenitors. The present review is first focused on the occurrence of spontaneous supernumerary hair cells and on nestin positive precursors found in the organ of Corti. A second approach to regenerating hair cells would be to find genes essential for their differentiation. This review will also focus on critical genes for embryonic hair cell formation such as the cell cycle related proteins, the Atoh1 gene and the Notch signaling pathway. Understanding mechanisms that underlie hair cell production is an essential prerequisite to defining therapeutic strategies to regenerate hair cells in the mature inner ear. [less ▲]

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See detailDépression et neuroplasticité.
Pitchot, William ULg; Polis, Marie-Hélène ULg; Belachew, Shibeshih ULg et al

in Revue Médicale de Liège (2008), 63

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See detailWhen HIV gets into the brain
Cuvelier, Marie-Laure ULg; Leonard, Philippe ULg; Rikir, Estelle ULg et al

in Revue Médicale de Liège (2008), 63(5-6), 338-341

Besides opportunistic infections, direct or indirect HIV-mediated lesions of cerebral vascular or neural cells can also occur during the natural course of HIV infection. The main non-infectious ... [more ▼]

Besides opportunistic infections, direct or indirect HIV-mediated lesions of cerebral vascular or neural cells can also occur during the natural course of HIV infection. The main non-infectious complications of HIV are cerebral lymphomas, cerebrovascular disorders, HIV dementia and myelitis. [less ▲]

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See detailHIV-related infections of the brain
Cuvelier, Marie-Laure ULg; Leonard, Philippe ULg; Rikir, Estelle ULg et al

in Revue Médicale de Liège (2008), 63(5-6), 342-348

During the natural course of human immunodeficiency virus infection, central nervous system insults are very common. They can consist of infectious complications, consequently to the collapse of the ... [more ▼]

During the natural course of human immunodeficiency virus infection, central nervous system insults are very common. They can consist of infectious complications, consequently to the collapse of the patient's immune system. Alternatively, direct or indirect HIV-mediated lesions of cerebral vascular or neural cells can also occur. It is crucial to detect HIV-related infectious complications since their prognosis will depend on early and accurate treatments. The diagnosis is generally made by means of magnetic resonance imaging and lumbar puncture. [less ▲]

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See detailAcquired tonsillar herniation and syringomyelia after pleural effusion aspiration: case report.
Scholsem, Martin ULg; Scholtes, Félix ULg; Belachew, Shibeshih ULg et al

in Neurosurgery (2008), 62(5), 1172-31173

OBJECTIVE: We present a case of brachial plexus avulsion and reconstructive surgery with cerebrospinal fluid leak between the cervical subarachnoid space and the pleural cavity responsible for tonsillar ... [more ▼]

OBJECTIVE: We present a case of brachial plexus avulsion and reconstructive surgery with cerebrospinal fluid leak between the cervical subarachnoid space and the pleural cavity responsible for tonsillar herniation and syringomyelia. CLINICAL PRESENTATION: A 17-year-old man presented with headaches when he was positioned upright, simultaneously with a persistent right pleural effusion for about 4 months after reconstructive surgery for a right brachial plexus avulsion. In addition, the headaches had worsened considerably after two aspirations of the pleural effusion. Magnetic resonance imaging (MRI) demonstrated signs of chronic intracranial hypotension and tonsillar herniation with a presyrinx cavity from vertebral level C1 to C7. None of those abnormalities were seen on the MRI scan obtained a few days after the initial trauma 7 months previously. Plexus brachial MRI confirmed the presence of a cerebrospinal fluid leak between the avulsed root of C8 and the pulmonary apex. INTERVENTION: The leak was treated by surgical closure of the dural tear of the C8 root. Postoperatively, the patient's headaches immediately resolved, and MRI 4 months later showed resolution of cerebellar tonsil herniation and regression of the syrinx. CONCLUSION: Resolution of acquired tonsillar herniation and syringomyelia can be achieved by closure of the dural tear responsible of the cerebrospinal fluid leak. [less ▲]

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See detailCdk2 is critical for proliferation and self-renewal of neural progenitor cells in the adult subventricular zone
Jablonska, Beata; Aguirre, Adan A.; Vandenbosch, Renaud ULg et al

in Journal of Cell Biology (2007), 179(6), 1231-1245

We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)-expressing progenitor cells of the ... [more ▼]

We investigated the function of cyclin-dependent kinase 2 (Cdk2) in neural progenitor cells during postnatal development. Chondroitin sulfate proteoglycan (NG2)-expressing progenitor cells of the subventricular zone (SVZ) show no significant difference in density and proliferation between Cdk2(-/-) and wild-type mice at perinatal ages and are reduced only in adult Cdk2(-/-) mice. Adult Cdk2(-/-) SVZ cells in culture display decreased self-renewal capacity and enhanced differentiation. Compensatory mechanisms in perinatal Cdk2(-/-) SVZ cells, which persist until postnatal day 15, involve increased Cdk4 expression that results in retinoblastoma protein inactivation. A subsequent decline in Cdk4 activity to wild-type levels in postnatal day 28 Cdk2(-/-) cells coincides with lower NG2(+) proliferation and self-renewal capacity similar to adult levels. Cdk4 silencing in perinatal Cdk2(-/-) SVZ cells abolishes Cdk4 up-regulation and reduces cell proliferation and self-renewal to adult levels. Conversely, Cdk4 overexpression in adult SVZ cells restores proliferative capacity to wildtype levels. Thus, although Cdk2 is functionally redundant in perinatal SVZ, it is important for adult progenitor cell proliferation and self-renewal through age-dependent regulation of Cdk4. [less ▲]

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See detailCdk2 Is Dispensable for Adult Hippocampal Neurogenesis
Vandenbosch, Renaud ULg; Borgs, Laurence ULg; Beukelaers, Pierre ULg et al

in Cell Cycle (Georgetown, Tex.) (2007), 6(24), 3065-9

Granule neurons of the dentate gyrus (DG) of the hippocampus undergo continuous renewal throughout life. Among cell cycle regulators, cyclin-dependent kinase 2 (Cdk2) is considered as a major regulator of ... [more ▼]

Granule neurons of the dentate gyrus (DG) of the hippocampus undergo continuous renewal throughout life. Among cell cycle regulators, cyclin-dependent kinase 2 (Cdk2) is considered as a major regulator of S-phase entry. We used Cdk2-deficient mice to decipher the requirement of Cdk2 for the generation of new neurons in the adult hippocampus. The quantification of cell cycle markers first revealed that the lack of Cdk2 activity does not influence spontaneous or seizure-induced proliferation of neural progenitor cells (NPC) in the adult DG. Using bromodeoxyuridine incorporation assays, we showed that the number of mature newborn granule neurons generated de novo was similar in both wild-type (WT) and Cdk2-deficient adult mice. Moreover, the apparent lack of cell output reduction in Cdk2(-/-) mice DG did not result from a reduction in apoptosis of newborn granule cells as analyzed by TUNEL assays. Our results therefore suggest that Cdk2 is dispensable for NPC proliferation, differentiation and survival of adult-born DG granule neurons in vivo. These data emphasize that functional redundancies between Cdks also occur in the adult brain at the level of neural progenitor cell cycle regulation during hippocampal neurogenesis. [less ▲]

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See detailTherapeutic armamentarium in neurology: the birth of a new era
Belachew, Shibeshih ULg; Magis, Delphine ULg; Lievens, Isabelle ULg et al

in Revue Médicale de Liège (2007), 62(5-6), 432-448

The field of neurology was long infamous for a lack of therapeutic options. How many of you have once thought: "Neurologists don't cure the disease, they admire it". But those days have passed into ... [more ▼]

The field of neurology was long infamous for a lack of therapeutic options. How many of you have once thought: "Neurologists don't cure the disease, they admire it". But those days have passed into history, and the field is now vibrant with new treatments and hope even for patients with the worst neurodegenerative diseases. We summarized in the present review the latest major advances in therapeutic principles and practice for some of the most frequent chronic neurological disorders such as headaches, epilepsy, multiple sclerosis, dementias, Parkinson's disease, sleep/wake disturbances and peripheral neuropathies. We cannot cure or prevent, but we can now halt or control symptoms and disease progression to provide physical and psychological relief, and a better quality of life for patients who suffer from these otherwise devastating neurological conditions. [less ▲]

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See detailIdentification of Sox17 as a transcription factor that regulates oligodendrocyte development
Sohn, Jiho; Natale, Joanne; Chew, Li-Jin et al

in Journal of Neuroscience (2006), 26(38), 9722-9735

Microarray analysis of oligodendrocyte lineage cells purified by fluorescence-activated cell sorting (FACS) from 2', 3'- cyclic nucleotide 3'-phosphodiesterase (CNP)-enhanced green fluorescent protein ... [more ▼]

Microarray analysis of oligodendrocyte lineage cells purified by fluorescence-activated cell sorting (FACS) from 2', 3'- cyclic nucleotide 3'-phosphodiesterase (CNP)-enhanced green fluorescent protein (EGFP) transgenic mice revealed Sox17 (SRY-box containing gene 17) gene expression to be coordinately regulated with that of four myelin genes during postnatal development. In CNP-EGFP-positive (CNP-EGFP(+)) cells, Sox17 mRNA and protein levels transiently increased between postnatal days 2 and 15, with white matter O4(+) preoligodendrocytes expressing greater Sox17 levels than Nkx2.2(+) ( NK2 transcription factor related, locus 2) NG2(+), or GalC(+) ( galactocerebroside) cells. In spinal cord, Sox17 protein expression was undetectable in the primary motor neuron domain between embryonic days 12.5 and 15.5 but was evident in Nkx2.2(+) and CCl+ cells. In cultured oligodendrocyte progenitor cells (OPCs), Sox17 levels were maximal in O4(+) cells and peaked during the phenotypic conversion from bipolar to multipolar. Parallel increases in Sox17 and p27 occurred before MBP protein expression, and Sox17 upregulation was prevented by conditions inhibiting differentiation. Sox17 down-regulation with small interfering RNAs increased OPC proliferation and decreased lineage progression after mitogen withdrawal, whereas Sox17 overexpression in the presence of mitogen had opposite effects. Sox17 overexpression enhanced myelin gene expression in OPCs and directly stimulated MBP gene promoter activity. These findings support important roles for Sox17 in controlling both oligodendrocyte progenitor cell cycle exit and differentiation. [less ▲]

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See detailClinical Case of the Month. Cerebrovascular Accident Related to Arterial Brachiocephalic Trunk Stenosis
Pirard, Laurence ULg; Belachew, Shibeshih ULg; Trotteur, Geneviève ULg et al

in Revue Médicale de Liège (2006), 61(7-8, Jul-Aug), 553-8

The authors report the case of a 47-year old man, admitted for syncope and left-sided motor deficit. Diagnostic investigations revealed a right middle cerebral artery embolic stroke, secondary to a ... [more ▼]

The authors report the case of a 47-year old man, admitted for syncope and left-sided motor deficit. Diagnostic investigations revealed a right middle cerebral artery embolic stroke, secondary to a critical stenosis of the arterial brachiocephalic trunk, harboring a floating thrombus. The treatment options for occlusive lesions of the brachiocephalic trunk are discussed, as well as the optimal delay between stroke and brain revascularization. [less ▲]

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See detailThe Yin and Yang of cell cycle progression and differentiation in the oligodendroglial lineage
Nguyen, Laurent ULg; Borgs, Laurence ULg; Vandenbosch, Renaud ULg et al

in Mental Retardation & Developmental Disabilities Research Reviews (2006), 12(2), 85-96

In white matter disorders such as leukodystrophies (LD), periventricular leucomalacia (PVL), or multiple sclerosis (MS), the hypomyelination or the remyelination failure by oligodendrocyte progenitor ... [more ▼]

In white matter disorders such as leukodystrophies (LD), periventricular leucomalacia (PVL), or multiple sclerosis (MS), the hypomyelination or the remyelination failure by oligodendrocyte progenitor cells involves errors in the sequence of events that normally occur during development when progenitors proliferate, migrate through the white matter, contact the axon, and differentiate into myelin-forming oligodendrocytes. Multiple mechanisms underlie the eventual progressive deterioration that typifies the natural history of developmental demyelination in LID and PVL and of adult-onset demyelination in MS. Over the past few years, pathophysiological studies have mostly focused on seeking abnormalities that impede oligodendroglial maturation at the level of migration, myelination, and survival. In contrast, there has been a strikingly lower interest for early proliferative and differentiation events that are likely to be equally critical for white matter development and myelin repair. This review highlights the Yin and Yang principles of interactions between intrinsic factors that coordinately regulate progenitor cell division and the onset of differentiation, i.e. the initial steps of oligodendrocyte lineage progression that are obviously crucial in health and diseases. (C) 2006 Wiley-Liss, Inc. [less ▲]

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See detailUntangling regulatory cues that control cell cycle progression and fate specification in the oligodendroglial lineage
Belachew, Shibeshih ULg

Thèse d’agrégation de l’enseignement supérieur (2005)

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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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