Merce Lliberia - Academia.edu (original) (raw)
Papers by Merce Lliberia
Acofar Revista De La Distribucion Farmaceutica Cooperativista, 1999
Copyright © 2014 Daniel Ortuño-Sahagún et al.This is an open access article distributed under t... more Copyright © 2014 Daniel Ortuño-Sahagún et al.This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the originalwork is properly cited. Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual’s Quality of Life (QOL). Although extensive research efforts in recent years have beenmade, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS]), which are currently used as an integral approach to study the aging proces...
ConferènCies (AulAri de lA fACultAt de fArmàCiA) 25/09 13.30-15.30 h: Presentació del seminari "P... more ConferènCies (AulAri de lA fACultAt de fArmàCiA) 25/09 13.30-15.30 h: Presentació del seminari "Passaport a la professió" i de l'assignatura de pràctiques en empreses, a càrrec d'una orientadora del SAE i de les coordinadores: Dra. Carmen Escolano i Dra. Encarna García 30/10 13.30-15.00 h: Com començar a buscar feina* 20/11 13.30-15.00h: la professió farmacèutica a través del Col•legi de farmacèutics de Barcelona 18/12 13.30-15.00 h: Com presentar un currículum vitae i una carta de motivació* 12/02 15.00-18.00 h: Workshop d'empreses químico-farmacèutiques 12/03 13.30-15.00 h: taula rodona: quins llocs de treball puc trobar a les empreses químico-farmacètiques?, a càrrec de diferents professionals 9/04 13.30-15.00 h: oportunitats a l'estranger* 14/05 13.30-15.00 h: màsters ofertats a la facultat de farmàcia, a càrrec de la Dra. Josefa Badia ACtivitAts d'orientACió (instAl•lACions del servei d'AtenCió A l'estudiAnt) visitar i conèixer els recursos del Club de feina-simulació personalitzada d'una entrevista de feina-Assessorament personalitzat del currículum vitae-Assessorament de la carta de motivació finalitat Aportar recursos a l'alumnat per a la recerca de pràctiques/feina, oportunitats a l'estranger, i de formació continuada. destinataris Alumnat de grau de Farmàcia (preferentment alumnes que hagin superat 150 crèdits), i de màsters de la Facultat de Farmàcia Preu Assistència sense reconeixement acadèmic: gratuït Assistència amb reconeixement acadèmic: 10 euros inscripció més informació Del 25 de setembre al 24 d'octubre de 2013 a: www.ub.edu/sae/orientacio/lorientacio-facultats.htm Servei d'Atenció a l'Estudiant (SAE)
La Facultat de Farmàcia ha realitzat accions encaminades a enfortir el contacte amb els centres d... more La Facultat de Farmàcia ha realitzat accions encaminades a enfortir el contacte amb els centres de secundària. En aquest context, es situa l'activitat Farmaestiu que es va celebrar del 16 al 18 de juny de 2014 a la Facultat de Farmàcia. Farmaestiu va estar promogut i organitzat per professors de diferents departaments de la Facultat de Farmàcia juntament amb l'equip deganal de la Facultat de Farmàcia i el Servei d'Atenció a l'Estudiant. Farmaestiu es va adreçar a estudiants de primer i segon dels batxillerat científic (els alumnes havien de cursar 1r de batxillerat durant el curs 2013-2014). La nota acadèmica de la segona avaluació havia d'estar per sobre del 7,5. El nombre de places ofertes va ser de 20. Es va rebre un nombre de sol•licituds molt superior i es va realitzar la selecció tenint en compte la nota acadèmica. Els alumnes van disposar d'un guió de pràctiques elaborat pels professors responsables dels tallers. En aquest guió es descrivien, acompanyats de gràfics, totes les activitats a desenvolupar i es donaven detalls per situar el tema en context i facilitar la compressió del Taller. Les sessions (CONFERÈNCIES I TALLERS) van estar organitzades i impartides per professors de la Facultat i s'indiquen a continuació.
El Farmaceutico Profesion Y Cultura, 2014
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2014
List of nonstandard abbreviations used in the paper: 3,4-methylenedioxymethamphetamine (MDMA); Ka... more List of nonstandard abbreviations used in the paper: 3,4-methylenedioxymethamphetamine (MDMA); Kainic acid (KA); calcium binding proteins (CaBP), parvalbumin (PV), calbindin (CB) and calretinin (CR).
Frontiers in cellular neuroscience, 2014
Pleiotrophin (PTN) is a secreted growth factor, and also a cytokine, associated with the extracel... more Pleiotrophin (PTN) is a secreted growth factor, and also a cytokine, associated with the extracellular matrix, which has recently starting to attract attention as a significant neuromodulator with multiple neuronal functions during development. PTN is expressed in several tissues, where its signals are generally related with cell proliferation, growth, and differentiation by acting through different receptors. In Central Nervous System (CNS), PTN exerts post-developmental neurotrophic and -protective effects, and additionally has been involved in neurodegenerative diseases and neural disorders. Studies in Drosophila shed light on some aspects of the different levels of regulatory control of PTN invertebrate homologs. Specifically in hippocampus, recent evidence from PTN Knock-out (KO) mice involves PTN functioning in learning and memory. In this paper, we summarize, discuss, and contrast the most recent advances and results that lead to proposing a PTN as a neuromodulatory molecule ...
Psychopharmacology, 2013
Objectives Addictive drugs produce forms of structural plasticity in the nucleus accumbens and pr... more Objectives Addictive drugs produce forms of structural plasticity in the nucleus accumbens and prefrontal cortex. The aim of this study was to investigate the impact of chronic MDMA exposure on pyramidal neurons in the CA1 region of hippocampus and drug-related spatial learning and memory changes. Methods and results Adolescent rats were exposed to saline or MDMA in a regime that mimicked chronic administration. One week later, when acquisition or reference memory was evaluated in a standard Morris water maze (MWM), no differences were obtained between groups. However, MDMAexposed animals performed better when the MWM was implemented under more difficult conditions. Animals of MDMA group were less anxious and were more prepared to take risks, as in the open field test they ventured more frequently into the central area. We have demonstrated that MDMA caused an increase in brain-derived neurotrophic factor (BDNF) expression. When spine density was evaluated, MDMA-treated rats presented a reduced density when compared with saline, but overall, training increased the total number of spines, concluding that in MDMA-group, training prevented a reduction in spine density or induced its recovery. Conclusions This study provides support for the conclusion that binge administration of MDMA, known to be associated to neurotoxic damage of hippocampal serotonergic terminals, increases BDNF expression and stimulates synaptic plasticity when associated with training. In these conditions, adolescent rats perform better in a more difficult water maze task under restricted conditions of learning and memory. The effect on this task could be modulated by other behavioural changes provoked by MDMA.
NeuroToxicology, 2009
Pentachlorophenol (PCP) (C(6)HCl(5)O) is a synthetic toxic organochloride fungicide for humans wh... more Pentachlorophenol (PCP) (C(6)HCl(5)O) is a synthetic toxic organochloride fungicide for humans which exhibit neurotoxic properties. In the present research, we describe the potential pathways implicated in PCP-induced apoptosis in an acute model of toxicity in rat cerebellar granule neurons (CGNs). In our experiments, acute exposure of CGNs to micromolar concentrations of PCP induced the transcriptional activity of genes related to the classical apoptosis pathway (caspase 3, caspase 8, Bad), oxidative stress and glutathione metabolism (glutathione peroxidase-1, catalase, glutathione-S-transferase-3 and superoxide dismutase-1), and mitogenic response (cyclin D1, cdk2, cdk4, cdkn2b). Results from Western blot also shown significative increases in the expression of cyclins D1, E and A and cdk4. The mitogenic response was also related to a significative increase in the phosphorylation of retinoblastoma protein (Rb). PCP would cause apoptosis up-regulating the transcriptional activity of p53 gene and also increasing their activation by phosphorylation, concomitant with a decrease in the sirtuin 1 content. In conclusion, acute exposure of CGNs to PCP induces the classical p53 apoptotic pathway, promotes the up-regulation of several genes related to oxidative stress and the over-expression of molecules involved in the cell cycle control.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2003
The consequences of the neurotoxic insult induced by 3,4-methylenedioxymethamphetamine (MDMA, an ... more The consequences of the neurotoxic insult induced by 3,4-methylenedioxymethamphetamine (MDMA, an amphetamine derivative with specific action on the serotonergic system) were compared with those of methamphetamine (a derivative with specific action on dopaminergic system) in rats. Both drugs induced a very similar loss of body weight, especially evident 24 h after treatment. Their hyperthermic profile was also very similar and was dependent on ambient temperature, corroborating the thermo-dysregulatory effect of both substances. Methamphetamine (four injections of 10 mg kg-1 s.c. at 2-h intervals) induced the loss of dopaminergic (35%) but not of serotonergic, terminals in the rat striatum and, simultaneously, a significant increase in striatal peripheraltype benzodiazepine receptor density, pointing to a glial reaction. Evidence for this drug-induced astrogliosis was the increased heat shock protein 27 (HSP27) expression in striatum, cortex and hippocampus. MDMA (20 mg kg-1 s.c. b.i.d. for 4 days) induced a similar dopaminergic lesion in the striatum 3 days posttreatment, which reversed 4 days later. An important neurotoxic effect on serotonergic terminals was also observed in the cortex, striatum and hippocampus 3 days post-treatment, which partially reversed 4 days later in the striatum and hippocampus. No microglial activation was noticeable at either 3 or 7 days after MDMA treatment. This lack of effect on microglial cells was assessed by [ 3 H]PK 11195 binding and OX-6 immunostaining, which were unchanged in the striatum and cortex after MDMA treatment. A nonsignificant tendency to increase was noted in the hippocampus 3 days after MDMA treatment. Furthermore, in MDMA-treated rats, neither HSP27 expression nor an increase in HSP27 immunoreactivity were detected. This result , together with the lack of increase in glial fibrilliary acidic protein (GFAP) immunoreactivity, indicate no astroglial activation at either 3 or 7 days post-treatment. Without microglial activation, an inflammatory process would not accompany the lesion induced by MDMA. The differences in glial activation between methamphetamine and MDMA observed in the present study could have implications for the prognosis of the injury induced by these drugs.
Mechanisms of Ageing and Development, 2005
Tau is a neuronal microtubule associated protein whose main biological functions are to promote m... more Tau is a neuronal microtubule associated protein whose main biological functions are to promote microtubule self-assembly by tubulin and to stabilize those already formed. Tau also plays an important role as an axonal microtubule protein. Tau is an amazing protein that plays a key role in cognitive processes, however, deposits of abnormal forms of tau are associated with several neurodegenerative diseases, including Alzheimer disease (AD), the most prevalent, and Chronic Traumatic Encephalopathy (CTE) and Traumatic Brain Injury (TBI), the most recently associated to abnormal tau. Tau post-translational modifications (PTMs) are responsible for its gain of toxic function. Alonso et al. (1996) were the first to show that the pathological tau isolated from AD brains has prion-like properties and can transfer its toxic function to the normal molecule. Furthermore, we reported that the pathological changes are associated with tau phosphorylation at Ser199 and 262 and Thr212 and 231. This pathological version of tau induces subcellular mislocalization in cultured cells and neurons, and translocates into the nucleus or accumulated in the perinuclear region of cells. We have generated a transgenic mouse model that expresses pathological human tau (PH-Tau) in neurons at two different concentrations (4% and 14% of the total endogenous tau). In this model, PH-Tau causes cognitive decline by at least two different mechanisms: one that involves the cytoskeleton with axonal disruption (at high concentration), and another in which the apparent neuronal morphology is not grossly affected, but the synaptic terminals are altered (at lower concentration). We will discuss the putative involvement of tau in proteostasis under these conditions. Understanding tau's biological activity on and off the microtubules will help shed light to the mechanism of neurodegeneration and of normal neuronal function.
Journal of Pineal Research, 2009
Journal of Neuroscience Research, 2000
European Journal of Pharmacology, 2009
Osteoblasts play a fundamental role in determining bone structure and function. These cells origi... more Osteoblasts play a fundamental role in determining bone structure and function. These cells originate from mesenchymal stem cells (MSCs) and through proliferation and differentiation develop into preosteoblasts and then into mature cells. Most of these cells undergo apoptosis before reaching their terminal differentiated stages of either osteocytes or bone lining cells. These processes, i.e. proliferation, differentiation, and apoptosis, are affected by systemic hormones and local factors. In addition, there are exogenous regulators, which can either be natural substances or synthetic compounds. This thesis describes investigations of the effects of several selected factors on proliferation, differentiation, and apoptosis of osteoblastic cells. The thesis is based on four papers: In the first paper, the effects of Sirt1 regulators, resveratrol (RSV), nicotinamide (NAM), and isonicotinamide (INM), on the commitment of mesenchymal stem cells (MSC) were studied. We found that the Sirt1 activators, RSV and INM, inhibited adipocyte formation and enhanced osteoblast differentiation, while the inhibitor NAM had the opposite effect. In the second paper, osteoblastic cells from different origins, mouse, rat, and human, were treated with 1α,25(OH) 2 D 3 and its analogue, 2-methylene-19-nor-(20S)-1α,25(OH) 2 D 3 (2MD). Species-dependent effects on cell growth and alkaline phosphatase (ALP) activity were clearly seen. In the third paper, we found that the expression of Interleukin-6 (IL-6) receptor increased during osteoblast differentiation. IL-6 acted as a differentiation accelerator in the early stage and an apoptosis inducer at late mature stage. In the forth paper, the effects of Sirt1 activators, RSV and INM, on proliferation and apoptosis of human osteosarcoma (OS) cells were studied. We found an inhibitory effect of Sirt1 activators on OS cells and showed a synergism between RSV and L-asparaginase (ASNase), which is a selective nutritional restrictor. In summary, the work presented in this thesis provides new information about the effects of two osteoblast differentiation regulators, 1α,25(OH) 2 D 3 and IL-6. Additionally, certain compounds affecting Sirt1 activity were found to influence osteoblast differentiation; RSV and INM which increase Sirt1 activity also had a profoundly negative effect on growth of OS cells in vitro. LIST OF PUBLICATIONS This thesis is based on the work of the following papers. They are referred to by their Roman numerals. I. Bäckesjö CM, Li Y, Lindgren U, and Haldosén LA. Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells. J Bone Miner Res 2006; 21: 993-1002. II. Li Y, Bäckesjö CM, Haldosén LA, and Lindgren U. Species difference exists in the effects of 1α,25(OH)2D3 and its analogue 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 (2MD) on osteoblastic cells. Accepted Manuscript, The Journal of Steroid Biochemistry and Molecular Biology.
European Journal of Pharmacology, 1996
The effect of MK-801 (dizocilpine) on the noradrenergic neurotransmission of the epididymal porti... more The effect of MK-801 (dizocilpine) on the noradrenergic neurotransmission of the epididymal portion of rat vas deferens has been investigated. This drug potentiated the electrically induced responses (46.6% +/- 5.09 at a concentration of 3.7 microM) and the contractile effect of exogenous noradrenaline with a concentration-dependent reduction of EC50 (from 0.99 +/- 0.11 microM to 0.06 +/- 0.01 microM). Moreover, MK-801 alone induced spontaneous contractile responses that were abolished by prazosin, not reversed by N-methyl-D-aspartate (NMDA) + glycine and that did not appear in organs obtained from reserpinized rats. In addition, MK-801 inhibited the [3H]noradrenaline uptake in slices from rat vas deferens (IC50 = 1.79 +/- 0.06 microM). Since these effects took place in the presence of magnesium and were sodium-dependent, a direct participation of the NMDA receptor complex can be ruled out, pointing to the inhibition of the cathecolamine uptake systems in the postganglionic sympathetic nerve endings as the most feasible mechanism.
Brain Research Protocols, 1999
The overexcitation of glutamate receptors is believed to be the cause of several neurodegenerativ... more The overexcitation of glutamate receptors is believed to be the cause of several neurodegenerative disorders. The determination of calcium fluxes, mitochondrial membrane potential (MMP) variations or the production of reactive oxygen species (ROS) in mammalian cells are usually measured during the development of potentially useful drugs that might interfere in the events induced by glutamate receptor activation. By using flow cytometry with dissociated cerebellar granule cells, we have developed a rapid and economical method to measure changes in biochemical parameters that are involved in neuronal cell death. The formation of intracellular ROS is measured using 2',7'-dichlorofluorescin diacetate (DCFH-DA). The mitochondrial membrane potential is assessed by the retention of rhodamine 123 (Rh123), a specific fluorescent cationic dye that is readily sequestered by active mitochondria, depending on their transmembrane potential. Finally, intracellular calcium increases are detected by using the calcium-selective indicator Indo-1. Cell viability is also assessed by using propidium iodide (PI) which stains DNA strands of permeabilized cells. This method might be useful for the screening of new drugs with potential neuroprotective activity, with improved cost/effectiveness ratio compared to other techniques.
Brain Research, 1997
Activation of NMDA receptors in dissociated cerebellar granule cells reduced mitochondrial membra... more Activation of NMDA receptors in dissociated cerebellar granule cells reduced mitochondrial membrane potential (MMP), as measured by rhodamine 123 fluorescence in a flow cytometer. This effect was inhibited by several NMDA-receptor antagonists with the following rank order of potency: MK-801 > PCP > TCP > dextrorphan > dichlorokynurenic acid > D-AP5 > dextromethorphan. Neither spermine nor arcaine modified the NMDA-induced reduction in MMP, whereas ifenprodil and eliprodil inhibited this response in the micromolar range. The mechanism responsible for the alteration of MMP mediated by NMDA was studied. Mepacrine and dibucaine prevented the MMP reduction induced by NMDA, as did W13 (calmodulin antagonist). In contrast, this effect was not blocked by cyclooxygenase or lipooxygenase inhibitors, H7 (a protein kinase C inhibitor) or nitroarginine (nitric oxide synthase inhibitor). These data suggest a direct interaction between NMDA-receptor activation and arachidonic acid formation, and indicate that NMDA receptor-mediated effect on MMP could involve arachidonic acid.
Acófar: Revista del Mundo Farmacéutico, 2002
... Resultado de la búsqueda, 1-1/1, Seleccionar todos Título: El resfriado común Autores: Pallàs... more ... Resultado de la búsqueda, 1-1/1, Seleccionar todos Título: El resfriado común Autores: PallàsLiberia, Mercè Revista: Acófar : Revista del Mundo Farmacéutico, 2002 DIC; (415) Página(s): 38-42 ISSN: 05677114. © UCM 2010, Biblioteca de la Universidad Complutense. ...
Acofar Revista De La Distribucion Farmaceutica Cooperativista, 1999
Copyright © 2014 Daniel Ortuño-Sahagún et al.This is an open access article distributed under t... more Copyright © 2014 Daniel Ortuño-Sahagún et al.This is an open access article distributed under the Creative CommonsAttribution License, which permits unrestricted use, distribution, and reproduction in anymedium, provided the originalwork is properly cited. Aging is a gradual, complex process in which cells, tissues, organs, and the whole organism itself deteriorate in a progressive and irreversible manner that, in the majority of cases, implies pathological conditions that affect the individual’s Quality of Life (QOL). Although extensive research efforts in recent years have beenmade, the anticipation of aging and prophylactic or treatment strategies continue to experience major limitations. In this review, the focus is essentially on the compilation of the advances generated by cellular expression profile analysis through proteomics studies (two-dimensional [2D] electrophoresis and mass spectrometry [MS]), which are currently used as an integral approach to study the aging proces...
ConferènCies (AulAri de lA fACultAt de fArmàCiA) 25/09 13.30-15.30 h: Presentació del seminari "P... more ConferènCies (AulAri de lA fACultAt de fArmàCiA) 25/09 13.30-15.30 h: Presentació del seminari "Passaport a la professió" i de l'assignatura de pràctiques en empreses, a càrrec d'una orientadora del SAE i de les coordinadores: Dra. Carmen Escolano i Dra. Encarna García 30/10 13.30-15.00 h: Com començar a buscar feina* 20/11 13.30-15.00h: la professió farmacèutica a través del Col•legi de farmacèutics de Barcelona 18/12 13.30-15.00 h: Com presentar un currículum vitae i una carta de motivació* 12/02 15.00-18.00 h: Workshop d'empreses químico-farmacèutiques 12/03 13.30-15.00 h: taula rodona: quins llocs de treball puc trobar a les empreses químico-farmacètiques?, a càrrec de diferents professionals 9/04 13.30-15.00 h: oportunitats a l'estranger* 14/05 13.30-15.00 h: màsters ofertats a la facultat de farmàcia, a càrrec de la Dra. Josefa Badia ACtivitAts d'orientACió (instAl•lACions del servei d'AtenCió A l'estudiAnt) visitar i conèixer els recursos del Club de feina-simulació personalitzada d'una entrevista de feina-Assessorament personalitzat del currículum vitae-Assessorament de la carta de motivació finalitat Aportar recursos a l'alumnat per a la recerca de pràctiques/feina, oportunitats a l'estranger, i de formació continuada. destinataris Alumnat de grau de Farmàcia (preferentment alumnes que hagin superat 150 crèdits), i de màsters de la Facultat de Farmàcia Preu Assistència sense reconeixement acadèmic: gratuït Assistència amb reconeixement acadèmic: 10 euros inscripció més informació Del 25 de setembre al 24 d'octubre de 2013 a: www.ub.edu/sae/orientacio/lorientacio-facultats.htm Servei d'Atenció a l'Estudiant (SAE)
La Facultat de Farmàcia ha realitzat accions encaminades a enfortir el contacte amb els centres d... more La Facultat de Farmàcia ha realitzat accions encaminades a enfortir el contacte amb els centres de secundària. En aquest context, es situa l'activitat Farmaestiu que es va celebrar del 16 al 18 de juny de 2014 a la Facultat de Farmàcia. Farmaestiu va estar promogut i organitzat per professors de diferents departaments de la Facultat de Farmàcia juntament amb l'equip deganal de la Facultat de Farmàcia i el Servei d'Atenció a l'Estudiant. Farmaestiu es va adreçar a estudiants de primer i segon dels batxillerat científic (els alumnes havien de cursar 1r de batxillerat durant el curs 2013-2014). La nota acadèmica de la segona avaluació havia d'estar per sobre del 7,5. El nombre de places ofertes va ser de 20. Es va rebre un nombre de sol•licituds molt superior i es va realitzar la selecció tenint en compte la nota acadèmica. Els alumnes van disposar d'un guió de pràctiques elaborat pels professors responsables dels tallers. En aquest guió es descrivien, acompanyats de gràfics, totes les activitats a desenvolupar i es donaven detalls per situar el tema en context i facilitar la compressió del Taller. Les sessions (CONFERÈNCIES I TALLERS) van estar organitzades i impartides per professors de la Facultat i s'indiquen a continuació.
El Farmaceutico Profesion Y Cultura, 2014
Progress in Neuro-Psychopharmacology and Biological Psychiatry, 2014
List of nonstandard abbreviations used in the paper: 3,4-methylenedioxymethamphetamine (MDMA); Ka... more List of nonstandard abbreviations used in the paper: 3,4-methylenedioxymethamphetamine (MDMA); Kainic acid (KA); calcium binding proteins (CaBP), parvalbumin (PV), calbindin (CB) and calretinin (CR).
Frontiers in cellular neuroscience, 2014
Pleiotrophin (PTN) is a secreted growth factor, and also a cytokine, associated with the extracel... more Pleiotrophin (PTN) is a secreted growth factor, and also a cytokine, associated with the extracellular matrix, which has recently starting to attract attention as a significant neuromodulator with multiple neuronal functions during development. PTN is expressed in several tissues, where its signals are generally related with cell proliferation, growth, and differentiation by acting through different receptors. In Central Nervous System (CNS), PTN exerts post-developmental neurotrophic and -protective effects, and additionally has been involved in neurodegenerative diseases and neural disorders. Studies in Drosophila shed light on some aspects of the different levels of regulatory control of PTN invertebrate homologs. Specifically in hippocampus, recent evidence from PTN Knock-out (KO) mice involves PTN functioning in learning and memory. In this paper, we summarize, discuss, and contrast the most recent advances and results that lead to proposing a PTN as a neuromodulatory molecule ...
Psychopharmacology, 2013
Objectives Addictive drugs produce forms of structural plasticity in the nucleus accumbens and pr... more Objectives Addictive drugs produce forms of structural plasticity in the nucleus accumbens and prefrontal cortex. The aim of this study was to investigate the impact of chronic MDMA exposure on pyramidal neurons in the CA1 region of hippocampus and drug-related spatial learning and memory changes. Methods and results Adolescent rats were exposed to saline or MDMA in a regime that mimicked chronic administration. One week later, when acquisition or reference memory was evaluated in a standard Morris water maze (MWM), no differences were obtained between groups. However, MDMAexposed animals performed better when the MWM was implemented under more difficult conditions. Animals of MDMA group were less anxious and were more prepared to take risks, as in the open field test they ventured more frequently into the central area. We have demonstrated that MDMA caused an increase in brain-derived neurotrophic factor (BDNF) expression. When spine density was evaluated, MDMA-treated rats presented a reduced density when compared with saline, but overall, training increased the total number of spines, concluding that in MDMA-group, training prevented a reduction in spine density or induced its recovery. Conclusions This study provides support for the conclusion that binge administration of MDMA, known to be associated to neurotoxic damage of hippocampal serotonergic terminals, increases BDNF expression and stimulates synaptic plasticity when associated with training. In these conditions, adolescent rats perform better in a more difficult water maze task under restricted conditions of learning and memory. The effect on this task could be modulated by other behavioural changes provoked by MDMA.
NeuroToxicology, 2009
Pentachlorophenol (PCP) (C(6)HCl(5)O) is a synthetic toxic organochloride fungicide for humans wh... more Pentachlorophenol (PCP) (C(6)HCl(5)O) is a synthetic toxic organochloride fungicide for humans which exhibit neurotoxic properties. In the present research, we describe the potential pathways implicated in PCP-induced apoptosis in an acute model of toxicity in rat cerebellar granule neurons (CGNs). In our experiments, acute exposure of CGNs to micromolar concentrations of PCP induced the transcriptional activity of genes related to the classical apoptosis pathway (caspase 3, caspase 8, Bad), oxidative stress and glutathione metabolism (glutathione peroxidase-1, catalase, glutathione-S-transferase-3 and superoxide dismutase-1), and mitogenic response (cyclin D1, cdk2, cdk4, cdkn2b). Results from Western blot also shown significative increases in the expression of cyclins D1, E and A and cdk4. The mitogenic response was also related to a significative increase in the phosphorylation of retinoblastoma protein (Rb). PCP would cause apoptosis up-regulating the transcriptional activity of p53 gene and also increasing their activation by phosphorylation, concomitant with a decrease in the sirtuin 1 content. In conclusion, acute exposure of CGNs to PCP induces the classical p53 apoptotic pathway, promotes the up-regulation of several genes related to oxidative stress and the over-expression of molecules involved in the cell cycle control.
Naunyn-Schmiedeberg's Archives of Pharmacology, 2003
The consequences of the neurotoxic insult induced by 3,4-methylenedioxymethamphetamine (MDMA, an ... more The consequences of the neurotoxic insult induced by 3,4-methylenedioxymethamphetamine (MDMA, an amphetamine derivative with specific action on the serotonergic system) were compared with those of methamphetamine (a derivative with specific action on dopaminergic system) in rats. Both drugs induced a very similar loss of body weight, especially evident 24 h after treatment. Their hyperthermic profile was also very similar and was dependent on ambient temperature, corroborating the thermo-dysregulatory effect of both substances. Methamphetamine (four injections of 10 mg kg-1 s.c. at 2-h intervals) induced the loss of dopaminergic (35%) but not of serotonergic, terminals in the rat striatum and, simultaneously, a significant increase in striatal peripheraltype benzodiazepine receptor density, pointing to a glial reaction. Evidence for this drug-induced astrogliosis was the increased heat shock protein 27 (HSP27) expression in striatum, cortex and hippocampus. MDMA (20 mg kg-1 s.c. b.i.d. for 4 days) induced a similar dopaminergic lesion in the striatum 3 days posttreatment, which reversed 4 days later. An important neurotoxic effect on serotonergic terminals was also observed in the cortex, striatum and hippocampus 3 days post-treatment, which partially reversed 4 days later in the striatum and hippocampus. No microglial activation was noticeable at either 3 or 7 days after MDMA treatment. This lack of effect on microglial cells was assessed by [ 3 H]PK 11195 binding and OX-6 immunostaining, which were unchanged in the striatum and cortex after MDMA treatment. A nonsignificant tendency to increase was noted in the hippocampus 3 days after MDMA treatment. Furthermore, in MDMA-treated rats, neither HSP27 expression nor an increase in HSP27 immunoreactivity were detected. This result , together with the lack of increase in glial fibrilliary acidic protein (GFAP) immunoreactivity, indicate no astroglial activation at either 3 or 7 days post-treatment. Without microglial activation, an inflammatory process would not accompany the lesion induced by MDMA. The differences in glial activation between methamphetamine and MDMA observed in the present study could have implications for the prognosis of the injury induced by these drugs.
Mechanisms of Ageing and Development, 2005
Tau is a neuronal microtubule associated protein whose main biological functions are to promote m... more Tau is a neuronal microtubule associated protein whose main biological functions are to promote microtubule self-assembly by tubulin and to stabilize those already formed. Tau also plays an important role as an axonal microtubule protein. Tau is an amazing protein that plays a key role in cognitive processes, however, deposits of abnormal forms of tau are associated with several neurodegenerative diseases, including Alzheimer disease (AD), the most prevalent, and Chronic Traumatic Encephalopathy (CTE) and Traumatic Brain Injury (TBI), the most recently associated to abnormal tau. Tau post-translational modifications (PTMs) are responsible for its gain of toxic function. Alonso et al. (1996) were the first to show that the pathological tau isolated from AD brains has prion-like properties and can transfer its toxic function to the normal molecule. Furthermore, we reported that the pathological changes are associated with tau phosphorylation at Ser199 and 262 and Thr212 and 231. This pathological version of tau induces subcellular mislocalization in cultured cells and neurons, and translocates into the nucleus or accumulated in the perinuclear region of cells. We have generated a transgenic mouse model that expresses pathological human tau (PH-Tau) in neurons at two different concentrations (4% and 14% of the total endogenous tau). In this model, PH-Tau causes cognitive decline by at least two different mechanisms: one that involves the cytoskeleton with axonal disruption (at high concentration), and another in which the apparent neuronal morphology is not grossly affected, but the synaptic terminals are altered (at lower concentration). We will discuss the putative involvement of tau in proteostasis under these conditions. Understanding tau's biological activity on and off the microtubules will help shed light to the mechanism of neurodegeneration and of normal neuronal function.
Journal of Pineal Research, 2009
Journal of Neuroscience Research, 2000
European Journal of Pharmacology, 2009
Osteoblasts play a fundamental role in determining bone structure and function. These cells origi... more Osteoblasts play a fundamental role in determining bone structure and function. These cells originate from mesenchymal stem cells (MSCs) and through proliferation and differentiation develop into preosteoblasts and then into mature cells. Most of these cells undergo apoptosis before reaching their terminal differentiated stages of either osteocytes or bone lining cells. These processes, i.e. proliferation, differentiation, and apoptosis, are affected by systemic hormones and local factors. In addition, there are exogenous regulators, which can either be natural substances or synthetic compounds. This thesis describes investigations of the effects of several selected factors on proliferation, differentiation, and apoptosis of osteoblastic cells. The thesis is based on four papers: In the first paper, the effects of Sirt1 regulators, resveratrol (RSV), nicotinamide (NAM), and isonicotinamide (INM), on the commitment of mesenchymal stem cells (MSC) were studied. We found that the Sirt1 activators, RSV and INM, inhibited adipocyte formation and enhanced osteoblast differentiation, while the inhibitor NAM had the opposite effect. In the second paper, osteoblastic cells from different origins, mouse, rat, and human, were treated with 1α,25(OH) 2 D 3 and its analogue, 2-methylene-19-nor-(20S)-1α,25(OH) 2 D 3 (2MD). Species-dependent effects on cell growth and alkaline phosphatase (ALP) activity were clearly seen. In the third paper, we found that the expression of Interleukin-6 (IL-6) receptor increased during osteoblast differentiation. IL-6 acted as a differentiation accelerator in the early stage and an apoptosis inducer at late mature stage. In the forth paper, the effects of Sirt1 activators, RSV and INM, on proliferation and apoptosis of human osteosarcoma (OS) cells were studied. We found an inhibitory effect of Sirt1 activators on OS cells and showed a synergism between RSV and L-asparaginase (ASNase), which is a selective nutritional restrictor. In summary, the work presented in this thesis provides new information about the effects of two osteoblast differentiation regulators, 1α,25(OH) 2 D 3 and IL-6. Additionally, certain compounds affecting Sirt1 activity were found to influence osteoblast differentiation; RSV and INM which increase Sirt1 activity also had a profoundly negative effect on growth of OS cells in vitro. LIST OF PUBLICATIONS This thesis is based on the work of the following papers. They are referred to by their Roman numerals. I. Bäckesjö CM, Li Y, Lindgren U, and Haldosén LA. Activation of Sirt1 decreases adipocyte formation during osteoblast differentiation of mesenchymal stem cells. J Bone Miner Res 2006; 21: 993-1002. II. Li Y, Bäckesjö CM, Haldosén LA, and Lindgren U. Species difference exists in the effects of 1α,25(OH)2D3 and its analogue 2-methylene-19-nor-(20S)-1,25-dihydroxyvitamin D3 (2MD) on osteoblastic cells. Accepted Manuscript, The Journal of Steroid Biochemistry and Molecular Biology.
European Journal of Pharmacology, 1996
The effect of MK-801 (dizocilpine) on the noradrenergic neurotransmission of the epididymal porti... more The effect of MK-801 (dizocilpine) on the noradrenergic neurotransmission of the epididymal portion of rat vas deferens has been investigated. This drug potentiated the electrically induced responses (46.6% +/- 5.09 at a concentration of 3.7 microM) and the contractile effect of exogenous noradrenaline with a concentration-dependent reduction of EC50 (from 0.99 +/- 0.11 microM to 0.06 +/- 0.01 microM). Moreover, MK-801 alone induced spontaneous contractile responses that were abolished by prazosin, not reversed by N-methyl-D-aspartate (NMDA) + glycine and that did not appear in organs obtained from reserpinized rats. In addition, MK-801 inhibited the [3H]noradrenaline uptake in slices from rat vas deferens (IC50 = 1.79 +/- 0.06 microM). Since these effects took place in the presence of magnesium and were sodium-dependent, a direct participation of the NMDA receptor complex can be ruled out, pointing to the inhibition of the cathecolamine uptake systems in the postganglionic sympathetic nerve endings as the most feasible mechanism.
Brain Research Protocols, 1999
The overexcitation of glutamate receptors is believed to be the cause of several neurodegenerativ... more The overexcitation of glutamate receptors is believed to be the cause of several neurodegenerative disorders. The determination of calcium fluxes, mitochondrial membrane potential (MMP) variations or the production of reactive oxygen species (ROS) in mammalian cells are usually measured during the development of potentially useful drugs that might interfere in the events induced by glutamate receptor activation. By using flow cytometry with dissociated cerebellar granule cells, we have developed a rapid and economical method to measure changes in biochemical parameters that are involved in neuronal cell death. The formation of intracellular ROS is measured using 2',7'-dichlorofluorescin diacetate (DCFH-DA). The mitochondrial membrane potential is assessed by the retention of rhodamine 123 (Rh123), a specific fluorescent cationic dye that is readily sequestered by active mitochondria, depending on their transmembrane potential. Finally, intracellular calcium increases are detected by using the calcium-selective indicator Indo-1. Cell viability is also assessed by using propidium iodide (PI) which stains DNA strands of permeabilized cells. This method might be useful for the screening of new drugs with potential neuroprotective activity, with improved cost/effectiveness ratio compared to other techniques.
Brain Research, 1997
Activation of NMDA receptors in dissociated cerebellar granule cells reduced mitochondrial membra... more Activation of NMDA receptors in dissociated cerebellar granule cells reduced mitochondrial membrane potential (MMP), as measured by rhodamine 123 fluorescence in a flow cytometer. This effect was inhibited by several NMDA-receptor antagonists with the following rank order of potency: MK-801 > PCP > TCP > dextrorphan > dichlorokynurenic acid > D-AP5 > dextromethorphan. Neither spermine nor arcaine modified the NMDA-induced reduction in MMP, whereas ifenprodil and eliprodil inhibited this response in the micromolar range. The mechanism responsible for the alteration of MMP mediated by NMDA was studied. Mepacrine and dibucaine prevented the MMP reduction induced by NMDA, as did W13 (calmodulin antagonist). In contrast, this effect was not blocked by cyclooxygenase or lipooxygenase inhibitors, H7 (a protein kinase C inhibitor) or nitroarginine (nitric oxide synthase inhibitor). These data suggest a direct interaction between NMDA-receptor activation and arachidonic acid formation, and indicate that NMDA receptor-mediated effect on MMP could involve arachidonic acid.
Acófar: Revista del Mundo Farmacéutico, 2002
... Resultado de la búsqueda, 1-1/1, Seleccionar todos Título: El resfriado común Autores: Pallàs... more ... Resultado de la búsqueda, 1-1/1, Seleccionar todos Título: El resfriado común Autores: PallàsLiberia, Mercè Revista: Acófar : Revista del Mundo Farmacéutico, 2002 DIC; (415) Página(s): 38-42 ISSN: 05677114. © UCM 2010, Biblioteca de la Universidad Complutense. ...