References of "Lakaye, Bernard"
     in
Bookmark and Share    
Full Text
See detailMolecular evolution of the CYTH superfamily of proteins
Bettendorff, Lucien ULg; Delvaux, David ULg; Kohn, Grégory ULg et al

in FEBS Journal (2012), 279(Suppl. s1), 438

Molecular evolution of the CYTH superfamily of proteins L. Bettendorff, D. Delvaux, G. Kohn, P. Wins, B. Lakaye GIGA-Neurosciences, University of Liège, Belgium The CYTH superfamily of proteins was named ... [more ▼]

Molecular evolution of the CYTH superfamily of proteins L. Bettendorff, D. Delvaux, G. Kohn, P. Wins, B. Lakaye GIGA-Neurosciences, University of Liège, Belgium The CYTH superfamily of proteins was named after the two founding members, the CYaB adenylyl cyclase from Aeromonas hydrophila and the human 25-kDa THiamine triphosphatase (ThTPase). Members of this superfamily of proteins exist in all organisms including bacteria, archaea, plants and animals (except in birds) and can be traced back to the Last Universal Common Ancestor. They are characterized by a consensus sequence including several charged residues involved in divalent cation and triphosphate binding. Indeed, all members of the CYTH family that are characterized act on triphosphate derivatives and require at least one divalent cation for catalysis. The Nitrosomonas europaea (1) and E.coli CYTH proteins are specific inorganic triphosphatases. We propose that inorganic triphosphate (PPPi), the most simple triphosphate compound that can be imagined, is the primitive substrate of CYTH proteins. Other enzyme activities such as adenylate cyclase (in A. hydrophila), mRNA triphosphatase (in fungi and protozoans) and ThTPase (in metazoans) activities are secondary acquisitions. We show that ThTPase activity is not limited to mammals, but Sea anemone and Zebrafish CYTH proteins are already specific ThTPases and the acquisition of this enzyme activity is linked to the presence of a Trp (W53 in mammalian ThTPases) residue involved in the binding of the thiazole heterocycle of the thiamine molecule. The importance of W53 for the specificity of mammalian ThTPases is confirmed by site-directed mutagenesis. Furthermore, we propose a conserved catalytic mechanism between inorganic triphosphatases and ThTPases, based on a catalytic dyad comprising a Lys and a Tyr residue, explaining the alkaline pH optimum of CYTH proteins. (1) Delvaux et al. J. Biol. Chem 286 (2011) 34023-35 [less ▲]

Detailed reference viewed: 65 (11 ULg)
Full Text
Peer Reviewed
See detailA specific inorganic triphosphatase from Nitrosomonas europaea: structure and catalytic mechanism
Delvaux, David ULg; Murty, Mamidana R.V.S; Gabelica, Valérie ULg et al

in Journal of Biological Chemistry (2011), 286

The CYTH superfamily of proteins is named after its two founding members, the CyaB adenylyl cyclase from Aeromonas hydrophila and the human 25-kDa thiamine triphosphatase. Because these proteins often ... [more ▼]

The CYTH superfamily of proteins is named after its two founding members, the CyaB adenylyl cyclase from Aeromonas hydrophila and the human 25-kDa thiamine triphosphatase. Because these proteins often form a closed β-barrel, they are also referred to as “Triphosphate Tunnel Metalloenzymes” (TTM). Functionally, they are characterized by their ability to bind triphosphorylated substrates and divalent metal ions. These proteins exist in most organisms and catalyze different reactions, depending on their origin. Here we investigate structural and catalytic properties of the recombinant TTM protein from Nitrosomonas europaea (NeuTTM), a 19-kDa protein. Crystallographic data show that it crystallizes as a dimer and that, in contrast to other TTM proteins, it has an open β-barrel structure. We demonstrate that NeuTTM is a highly specific inorganic triphosphatase, hydrolyzing tripolyphosphate (PPPi) with high catalytic efficiency in the presence of Mg2+. These data are supported by native mass spectrometry analysis showing that the enzyme binds PPPi (and Mg-PPPi) with high affinity (Kd < 1.5 μM), while it has a low affinity for ATP or thiamine triphosphate. In contrast to Aeromonas and Yersinia CyaB proteins, NeuTTM has no adenylyl cyclase activity, but it shares several properties with other enzymes of the CYTH superfamily, e.g. heat-stability, alkaline pH optimum and inhibition by Ca2+ and Zn2+ ions. We suggest a catalytic mechanism involving a catalytic dyad formed by K52 and Y28. The present data provide the first characterization of a new type of phosphohydrolase (unrelated to pyrophosphatases or exopolyphosphatases), able to hydrolyze inorganic triphosphate with high specificity. [less ▲]

Detailed reference viewed: 95 (30 ULg)
Full Text
Peer Reviewed
See detailThiamine Status in Humans and Content of Phosphorylated Thiamine Derivatives in Biopsies and Cultured Cells
Gangolf, Marjorie ULg; Czerniecki, Jan; Radermecker, Marc ULg et al

in PLoS ONE (2010), 5(10), 13616

Background Thiamine (vitamin B1) is an essential molecule for all life forms because thiamine diphosphate (ThDP) is an indispensable cofactor for oxidative energy metabolism. The less abundant thiamine ... [more ▼]

Background Thiamine (vitamin B1) is an essential molecule for all life forms because thiamine diphosphate (ThDP) is an indispensable cofactor for oxidative energy metabolism. The less abundant thiamine monophosphate (ThMP), thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP), present in many organisms, may have still unidentified physiological functions. Diseases linked to thiamine deficiency (polyneuritis, Wernicke-Korsakoff syndrome) remain frequent among alcohol abusers and other risk populations. This is the first comprehensive study on the distribution of thiamine derivatives in human biopsies, body fluids and cell lines. Methodology and Principal Findings Thiamine derivatives were determined by HPLC. In human tissues, the total thiamine content is lower than in other animal species. ThDP is the major thiamine compound and tissue levels decrease at high age. In semen, ThDP content correlates with the concentration of spermatozoa but not with their motility. The proportion of ThTP is higher in humans than in rodents, probably because of a lower 25-kDa ThTPase activity. The expression and activity of this enzyme seems to correlate with the degree of cell differentiation. ThTP was present in nearly all brain and muscle samples and in ~60% of other tissue samples, in particular fetal tissue and cultured cells. A low ([ThTP]+[ThMP])/([Thiamine]+[ThMP]) ratio was found in cardiovascular tissues of patients with cardiac insufficiency. AThTP was detected only sporadically in adult tissues but was found more consistently in fetal tissues and cell lines. Conclusions and Significance The high sensitivity of humans to thiamine deficiency is probably linked to low circulating thiamine concentrations and low ThDP tissue contents. ThTP levels are relatively high in many human tissues, as a result of low expression of the 25-kDa ThTPase. Another novel finding is the presence of ThTP and AThTP in poorly differentiated fast-growing cells, suggesting a hitherto unsuspected link between these compounds and cell division or differentiation. [less ▲]

Detailed reference viewed: 74 (26 ULg)
Full Text
Peer Reviewed
See detailMajor impairments of glutamatergic transmission and long term synaptic plasticity in the hippocampus of mice lacking the melanin-concentrating hormone receptor-1
Pachoud, Bastien; Adamantidis, Antoine ULg; Ravassard, Pascal et al

in Journal of Neurophysiology (2010), 104

Detailed reference viewed: 48 (9 ULg)
Full Text
Peer Reviewed
See detailTetracycline-controlled transgene activation using the ROSA26-iM2-GFP knock-in mouse strain permits GFP monitoring of DOX-regulated transgene-expression
Wortge, Simone; Eshkind, Leonid; Cabezas-Wallscheid, Nina et al

in BMC Developmental Biology (2010), 10

Detailed reference viewed: 29 (1 ULg)
Full Text
Peer Reviewed
See detailDistribution of EFHC1 or myoclonin 1 in mouse neural structures
Leon, Christine ULg; de Nijs, Laurence ULg; Chanas, Grazyna et al

in Epilepsy Research (2010), 88

Detailed reference viewed: 20 (6 ULg)
Full Text
See detailEthanol-induced behaviors in mice genetically deficient in MCH1 receptors
Didone, Vincent ULg; Tirelli, Ezio ULg; Quertemont, Etienne ULg et al

in Alcoholism, Clinical & Experimental Research (2010), 34(8), 93-93

Detailed reference viewed: 37 (2 ULg)
Full Text
Peer Reviewed
See detailEffects of the H(3) receptor inverse agonist thioperamide on cocaine-induced locomotion in mice: role of the histaminergic system and potential pharmacokinetic interactions.
Brabant, Christian ULg; Alleva, Livia ULg; Grisar, Thierry ULg et al

in Psychopharmacology (2009), 202(4), 673-87

RATIONALE: Previous studies have shown that intraperitoneal injections of thioperamide, an imidazole-based H(3) receptor inverse agonist that enhances histamine release in the brain, potentiate cocaine ... [more ▼]

RATIONALE: Previous studies have shown that intraperitoneal injections of thioperamide, an imidazole-based H(3) receptor inverse agonist that enhances histamine release in the brain, potentiate cocaine-induced hyperlocomotion. The present study examined the involvement of the histaminergic system in these effects of thioperamide in mice. MATERIALS AND METHODS: We investigated whether immepip, a selective H(3) agonist, could reverse the potentiating effects of thioperamide. Moreover, the non-imidazole H(3) inverse agonist A-331440 was tested on the locomotor effects of cocaine. Using high-performance liquid chromatography with ultraviolet detection, cocaine plasma concentrations were measured to study potential drug-drug interactions between thioperamide and cocaine. Finally, thioperamide was tested on the locomotor effects of cocaine in histamine-deficient knockout mice in order to determine the contribution of histamine to the modulating effects of thioperamide. RESULTS: Thioperamide potentiated cocaine-induced hyperlocomotion in normal mice, and to a higher extent, in histamine-deficient knockout mice. A-331440 only slightly affected the locomotor effects of cocaine. Immepip did not alter cocaine-induced hyperactivity but significantly reduced the potentiating actions of thioperamide on cocaine's effects. Finally, plasma cocaine concentrations were more elevated in mice treated with thioperamide than in mice that received cocaine alone. CONCLUSIONS: The present results indicate that histamine released by thioperamide through the blockade of H(3) autoreceptors is not involved in the ability of this compound to potentiate cocaine induced-hyperactivity. Our data suggest that thioperamide, at least at 10 mg/kg, increases cocaine-induced locomotion through the combination of pharmacokinetic effects and the blockade of H(3) receptors located on non-histaminergic neurons. [less ▲]

Detailed reference viewed: 103 (16 ULg)
See detailCytoskeletal genes and idiopathic epilepsies
Lakaye, Bernard ULg; de Nijs, Laurence ULg; Leon, Christine et al

in Schwartzkroin, A. (Ed.) Encyclopedia of Basic Epilepsy Research (2009)

Detailed reference viewed: 11 (3 ULg)
Full Text
Peer Reviewed
See detailMelanin-concentrating hormone and immune function
Lakaye, Bernard ULg; Coumans, Bernard ULg; Harray, Sophie ULg et al

in Peptides (2009), 30

To date,melanin-concentrating hormone (MCH) has been generally considered as peptide acting almost exclusively in the central nervous system. In the present paper, we revise the experimental evidence ... [more ▼]

To date,melanin-concentrating hormone (MCH) has been generally considered as peptide acting almost exclusively in the central nervous system. In the present paper, we revise the experimental evidence, demonstrating that MCH and its receptors are expressed by cells of the immune system and directly influence the response of these cells in some circumstances. This therefore supports the idea that, as with other peptides, MCH could be considered as a modulator of the immune system. Moreover, we suggest that this could have important implications in several immune-mediated disorders and affirm that there is a clear need for further investigation [less ▲]

Detailed reference viewed: 38 (8 ULg)
Full Text
Peer Reviewed
See detailEFHC1 interacts with microtubules to regulate cell division and cortical development
de Nijs, Laurence ULg; Leon, Christine ULg; Nguyen, Laurent ULg et al

in Nature Neuroscience (2009), 12(10), 1266-74

Mutations in the EFHC1 gene are linked to juvenile myoclonic epilepsy (JME), one of the most frequent forms of idiopathic generalized epilepsies. JME is associated with subtle alterations of cortical and ... [more ▼]

Mutations in the EFHC1 gene are linked to juvenile myoclonic epilepsy (JME), one of the most frequent forms of idiopathic generalized epilepsies. JME is associated with subtle alterations of cortical and subcortical architecture, but the underlying pathological mechanism remains unknown. We found that EFHC1 is a microtubule-associated protein involved in the regulation of cell division. In vitro, EFHC1 loss of function disrupted mitotic spindle organization, impaired M phase progression, induced microtubule bundling and increased apoptosis. EFHC1 impairment in the rat developing neocortex by ex vivo and in utero electroporation caused a marked disruption of radial migration. We found that this effect was a result of cortical progenitors failing to exit the cell cycle and defects in the radial glia scaffold organization and in the locomotion of postmitotic neurons. Therefore, we propose that EFHC1 is a regulator of cell division and neuronal migration during cortical development and that disruption of its functions leads to JME [less ▲]

Detailed reference viewed: 127 (32 ULg)
Full Text
Peer Reviewed
See detailAmphetamine- and cocaine-induced conditioned place preference and concomitant psychomotor sensitization in mice with genetically inactivated melanin-concentrating hormone MCH(1) receptor.
Tyhon, Amélie ULg; Lakaye, Bernard ULg; Adamantidis, Antoine ULg et al

in European Journal of Pharmacology (2008), 599(1-3), 72-80

The melanin-concentrating hormone MCH(1) receptor has been proposed to exert an inhibitory control on monoaminergic (especially dopaminergic) activity within the mesolimbic system, which underpins drug ... [more ▼]

The melanin-concentrating hormone MCH(1) receptor has been proposed to exert an inhibitory control on monoaminergic (especially dopaminergic) activity within the mesolimbic system, which underpins drug seeking and reward. That hypothesis predicts that an inactivation of these receptors should enhance the sensitivity to drug rewarding effects. To test that prediction, we examined the propensity of mice lacking the melanin-concentrating receptor (MCH(1) KO) and their intact counterparts (WT) to form cocaine- and amphetamine-induced conditioned place preference. The conditioned rewarding effects induced by 0.375, 0.75, 1.5 and 3 mg/kg amphetamine were assessed in two sub-experiments and those induced by 1, 2, 4 and 8 mg/kg cocaine in two other sub-experiments. All mice were tested under saline for place preference 24 h following four every-other-day conditioning trials and an initial pre-conditioning session under saline. Most of the cocaine and amphetamine doses induced place preference, but without any genotype difference being revealed. Also, none of the cocaine doses induced psychomotor sensitization during conditioning, whereas amphetamine generated clear-cut dose-dependent sensitization in both genotypes. Albeit MCH(1) KO mice exhibited higher levels of psychomotor activation, the rates of sensitization were comparable across genotypes at 1.5 and 3 mg/kg amphetamine. Moreover, 0.375 and especially 0.75 mg/kg amphetamine produced a slight but yet significant sensitization in MCH(1) KO but not in their WT counterparts. Despite such an effect, the results cannot be considered as unambiguously supportive of the tested prediction. [less ▲]

Detailed reference viewed: 105 (3 ULg)
Full Text
Peer Reviewed
See detailDeletion of Melanin-Concentrating Hormone Receptor-1 gene accentuates D-amphetamine-induced psychomotor activation but neither the subsequent development of sensitization nor the expression of conditioned activity in mice
Tyhon, Amélie ULg; Lakaye, Bernard ULg; Grisar, Thierry ULg et al

in Pharmacology, Biochemistry & Behavior (2008), 88

The present study aimed to test the hypothesis that mice lacking the MCHR1 receptor (Melanin-Concentrating Hormone Receptor-1) present an elevated vulnerability towards the neurobehavioural effects of D ... [more ▼]

The present study aimed to test the hypothesis that mice lacking the MCHR1 receptor (Melanin-Concentrating Hormone Receptor-1) present an elevated vulnerability towards the neurobehavioural effects of D-amphetamine, presumably due to previously established up-regulations of dopamine D1 receptors in these mice. We examined the psychomotor effects of five once-daily injections of 1.5 and 3 mg/kg D-amphetamine (i.p.) or ten once-daily injections of 2.25 mg/kg D-amphetamine in knockout (KO) mice lacking the MCHR1 receptor. The first injection of Damphetamine induced a greater psychomotor response amongst the KO mice at 2.25 and 3.0 mg/kg. On all subsequent D-amphetamine injections, KO mice still showed greater levels of psychomotor activity than the WT mice, but with no between-genotype difference in the rate of development of sensitization (similar slopes of the curves). Furthermore, 24 h after the last injection of 2.25 mg/kg D-amphetamine both genotypes exhibited a significant post-sensitization conditioned activity. Thus, MCHR1 receptors are likely not deeply involved in the mechanisms of induction of sensitization and related conditioned activity induced by D-amphetamine, albeit our results confirm a contribution of these receptors to the mechanisms of the acute effects of that drug, possibly via an inhibitory action on the dopaminergic mesolimbic system. Our results do not support the hypothesis of a functional contribution of MCHR1 receptors to the addictive effects of D-amphetamine [less ▲]

Detailed reference viewed: 27 (3 ULg)
Full Text
Peer Reviewed
See detailAdenylate Kinase-Independent Thiamine Triphosphate Accumulation under Severe Energy Stress in Escherichia Coli
Gigliobianco, Tiziana ULg; Lakaye, Bernard ULg; Makarchikov, Alexander F et al

in BMC Microbiology (2008), 8

BACKGROUND: Thiamine triphosphate (ThTP) exists in most organisms and might play a role in cellular stress responses. In E. coli, ThTP is accumulated in response to amino acid starvation but the mechanism ... [more ▼]

BACKGROUND: Thiamine triphosphate (ThTP) exists in most organisms and might play a role in cellular stress responses. In E. coli, ThTP is accumulated in response to amino acid starvation but the mechanism of its synthesis is still a matter of controversy. It has been suggested that ThTP is synthesized by an ATP-dependent specific thiamine diphosphate kinase. However, it is also known that vertebrate adenylate kinase 1 catalyzes ThTP synthesis at a very low rate and it has been postulated that this enzyme is responsible for ThTP synthesis in vivo. RESULTS: Here we show that bacterial, as vertebrate adenylate kinases are able to catalyze ThTP synthesis, but at a rate more than 106-fold lower than ATP synthesis. This activity is too low to explain the high rate of ThTP accumulation observed in E. coli during amino acid starvation. Moreover, bacteria from the heat-sensitive CV2 strain accumulate high amounts of ThTP (>50% of total thiamine) at 37 degrees C despite complete inactivation of adenylate kinase and a subsequent drop in cellular ATP. CONCLUSION: These results clearly demonstrate that adenylate kinase is not responsible for ThTP synthesis in vivo. Furthermore, they show that E. coli accumulate large amounts of ThTP under severe energy stress when ATP levels are very low, an observation not in favor of an ATP-dependent mechanisms for ThTP synthesis. [less ▲]

Detailed reference viewed: 90 (23 ULg)
Full Text
Peer Reviewed
See detailSleep architecture of the melanin-concentrating hormone receptor 1-knockout mice
Adamantidis, Antoine ULg; Salvert, D.; Goutagny, R. et al

in European Journal of Neuroscience (2008), 27(7), 1793-800

Growing amounts of data indicate involvement of the posterior hypothalamus in the regulation of sleep, especially paradoxical sleep (PS). Accordingly, we previously showed that the melanin-concentrating ... [more ▼]

Growing amounts of data indicate involvement of the posterior hypothalamus in the regulation of sleep, especially paradoxical sleep (PS). Accordingly, we previously showed that the melanin-concentrating hormone (MCH)-producing neurons of the rat hypothalamus are selectively activated during a PS rebound. In addition, intracerebroventricular infusion of MCH increases total sleep duration, suggesting a new role for MCH in sleep regulation. To determine whether activation of the MCH system promotes sleep, we studied spontaneous sleep and its homeostatic regulation in mice with deletion of the MCH-receptor 1 gene (MCH-R1– ⁄ – vs. MCH-R1+ ⁄ +) and their behavioural response to modafinil, a powerful antinarcoleptic drug. Here, we show that the lack of functional MCH-R1 results in a hypersomniac-like phenotype, both in basal conditions and after total sleep deprivation, compared to wild-type mice. Further, we found that modafinil was less potent at inducing wakefulness in MCH-R1– ⁄ – than in MCH-R1+ ⁄ + mice. We report for the first time that animals with genetically inactivated MCH signaling exhibit altered vigilance state architecture and sleep homeostasis. This study also suggests that the MCH system may modulate central pathways involved in the wake-promoting effect of modafinil [less ▲]

Detailed reference viewed: 62 (7 ULg)
Full Text
Peer Reviewed
See detailEffect of ppMCH derived peptides on PBMC proliferation and cytokine expression
Coumans, Bernard ULg; Grisar, Thierry ULg; Nahon, J. L. et al

in Regulatory Peptides (2007), 143(1-3), 104-108

The mRNA encoding prepro-Melanin concentrating hormone (ppMCH) is mainly expressed in the central nervous system but has also been detected at lower amount in many peripheral tissues including spleen and ... [more ▼]

The mRNA encoding prepro-Melanin concentrating hormone (ppMCH) is mainly expressed in the central nervous system but has also been detected at lower amount in many peripheral tissues including spleen and thymus. At the peptide level however, several forms of the precursor can be detected in these tissues and are sometimes expressed at similar levels compared to brain. In the present work, we have studied the in vitro action of a wide range of concentration (1 nM to 1 microM) of the different peptides encoded by ppMCH i.e. neuropeptide glycine-glutamic acid (NGE), neuropeptide glutamic acid-isoleucine (NEI), Melanin concentrating hormone (MCH) and the dipeptide NEI-MCH on peripheral blood mononuclear cells (PBMC) proliferation and cytokine production following anti-CD3 stimulation. Among them only MCH decreased PBMC proliferation with a maximal effect of 35% at 100 nM. Moreover as demonstrated by using ELISA, MCH significantly decreases IL-2 production by 25% but not IL-4, INF-gamma or TNF-alpha expression. Interestingly, exogenous IL-2 decreases significantly MCH-mediated inhibition, suggesting that it is an important downstream mediator of MCH action. Finally, we showed that after 7 to 9 days of incubation, MCH also inhibits proliferation of non-stimulated PBMC. Altogether, these data demonstrate that fully mature MCH modulates proliferation of anti-CD3 stimulated PBMC partially through regulation of IL-2 production. [less ▲]

Detailed reference viewed: 37 (0 ULg)
Full Text
Peer Reviewed
See detailAlcohol drinking in MCH receptor-1-deficient mice
Duncan, E. A.; Sorrell, J. E.; Adamantidis, Antoine ULg et al

in Alcoholism, Clinical & Experimental Research (2007), 31(8), 1325-1337

Background: Recently, we demonstrated that exogenous melanin-concentrating hormone (MCH) increases alcohol drinking in rats when administered into the brain. However, because the physiological relevance ... [more ▼]

Background: Recently, we demonstrated that exogenous melanin-concentrating hormone (MCH) increases alcohol drinking in rats when administered into the brain. However, because the physiological relevance of this finding is unclear, we tested the hypothesis that endogenous MCH signaling enhances alcohol consumption. Methods: Alcohol intake was assessed in male and female wildtype (WT), heterozygous (HET), and homozygous MCH receptor-1-deficient (KO) mice. Mice were given 24-hour access to a series of alcohol-containing solutions. Following this, the mice were given limited (1-hour) access to 10% alcohol. Finally, mice were allowed 24-hour access to sucrose/quinine as a caloric control and a means to assess taste preference. A naive cohort of male WT and KO mice was tested for alcohol clearance following intraperitoneal administration of 3 g/kg alcohol. Another naive cohort of female mice was utilized to confirm that intracerebroventricular administration of MCH (5 mu g) would augment alcohol drinking in mice. Results: Exogenous MCH enhanced 10% alcohol consumption in mice (saline=0.45 +/- 0.08 g/kg, 5 mu g MCH=0.94 +/- 0.20 g/kg). Male KO mice consumed more 10% alcohol (11.50 +/- 1.31 g/kg) than WT (6.26 +/- 1.23 g/kg) and HET mice (6.49 +/- 1.23 g/kg) during ad libitum access. However, alcohol intake was similar among genotypes during 1 hour daily access. Male KO mice tended to consume less 17.75% sucrose+1.3 mM quinine than controls (WT=10.5 +/- 3.6, HET=7.5 +/- 1.7, KO=4.4 +/- 0.9 g/kg). Alcohol metabolism was similar between WT and KO mice. Conclusions: The finding that male KO consume more alcohol than WT and HET mice, are reminiscent of the counterintuitive reports that KO mice are hyperphagic and yet eat more when administered exogenous MCH. Changes in taste preference or alcohol metabolism do not appear to be important for the increased alcohol drinking in KO mice. [less ▲]

Detailed reference viewed: 64 (1 ULg)
Full Text
Peer Reviewed
See detailMice lacking the melanin-concentrating hormone receptor-1 exhibit an atypical psychomotor susceptibility to cocaine and no conditioned cocaine response
Tyhon, Amélie ULg; Adamantidis, Antoine ULg; Foidart, Agnès ULg et al

in Behavioural Brain Research (2006), 173(1), 94-103

The present study aimed at characterizing the acute and intermittent psychomotor responsiveness to cocaine in mice lacking the MCHR1 receptor, which is thought to modulate the mesocorticolimbic sytem ... [more ▼]

The present study aimed at characterizing the acute and intermittent psychomotor responsiveness to cocaine in mice lacking the MCHR1 receptor, which is thought to modulate the mesocorticolimbic sytem functioning [Smith DG, Tzavara ET, Shaw J, Luecke S, Wade M, Davis R, et al. Mesolimbic dopamine super-sensitivity in melanin-concentrating hormone-1 receptor deficient mice. J Neurosci 2005;25:914-22]. On a first free-drug session, MCHR1-deficient mice exhibited significantly higher levels of locomotor activity elicited by the novelty of the test chambers than their wild-type counterparts. On the following day session, a first injection of 6 or 12mg/kg cocaine induced comparable dose-related psychomotor activations in both genotypes, without significant difference in the relative increase in locomotion. Over the following eight once-daily test sessions, the slight psychomotor increase induced by 6mg/kg was equivalent in both genotypes and constant over the sessions. At 12mg/kg, cocaine induced a clear-cut incremental responsiveness to cocaine in both genotypes on the three first sessions; on the following sessions, only the wild-types displayed an incremental responsiveness until the last session, a sensitized effect that was confirmed for the wild-types but not for the knockouts on a subsequent sensitization test (cocaine challenge). Finally, the knockouts did not exhibit any sign of cocaine-conditioning (saline challenge), contrarily to the wild-types. It is speculated that MCHR1 may contribute to the neurobiological mechanisms of conditioned cocaine-induced psychomotor effects, possibly to those underpinning sensitization, and to a lesser extent to those sub-serving acute pharmacological cocaine action. [less ▲]

Detailed reference viewed: 67 (24 ULg)
Full Text
Peer Reviewed
See detailEFHC1, a protein mutated in juvenile myoclonic epilepsy, associates with the mitotic spindle through its N-terminus
de Nijs, Laurence ULg; Lakaye, Bernard ULg; Coumans, Bernard ULg et al

in Experimental Cell Research (2006), 312(15), 2872-2879

A novel gene, EFHC1, mutated in juvenile myoclonic epilepsy (JME) encodes a protein with three DM10 domains of unknown function and one putative EF-hand motif. To study the properties of EFHC1, we ... [more ▼]

A novel gene, EFHC1, mutated in juvenile myoclonic epilepsy (JME) encodes a protein with three DM10 domains of unknown function and one putative EF-hand motif. To study the properties of EFHC1, we expressed EGFP-tagged protein in various cell lines. In interphase cells, the fusion protein was present in the cytoplasm and in the nucleus with specific accumulation at the centrosome. During mitosis EGFP-EFHC1 colocalized with the mitotic spindle, especially at spindle poles and with the midbody during cytokinesis. Using a specific antibody, we demonstrated the same distribution of the endogenous protein. Deletion analyses revealed that the N-terminal region of EFHC1 is crucial for the association with the mitotic spindle and the midbody. Our results suggest that EFHC1 could play an important role during cell division. (c) 2006 Elsevier Inc. All rights reserved. [less ▲]

Detailed reference viewed: 47 (6 ULg)