El profesional de la información y su capacitación permanente en un entorno signado por los cambios

Reflections on the future of the information professional at the end of the 20th century. While putting pressure in permanent and formal education, perception of the social and cultural role and regional integration strategies, current changes will affect positively the status of the librarian and new roles will emerge. Education and training, research and interdisciplinary interaction are the premises from which the new information manager of the 21st century is to be bornReflexión sobre el futuro del profesional de la información y los retos que debe afrontar a finales del siglo XX. Se intenta demostrar que los cambios afectarán positivamente al estatus del bibliotecólogo, le añadirán nuevos roles a los ya existentes y plantearán desafíos en su formación, su función social y cultural y sus estrategias de integración regional. La formación, la investigación en el área de la información y un mayor vínculo interdisciplinario son premisas de las que emergerá el gestor de la información que el siglo XXI demanda. (Autor

Analyse du rôle des processus moteurs, motivationnels et cognitifs dans l'akinésie (approches comportementale et neuroanatomique chez le rat traité par la 6-OHDA)

L'akinésie est l'un des symptômes caractéristiques de la maladie de Parkinson. Akinésie se traduit littéralement par absence de mouvement. L'existence de l'akinésie dans la schizophrénie et la dépression suppose un aspect psychomoteur. Par ailleurs, ces pathologies sont associées à un déséquilibre dopaminergique dans le système nerveux central. Nous avons émis l'hypothèse que le dysfonctionnement des différentes voies dopaminergiques pourrait être à l'origine de l'akinésie. Nous avons utilisé un modèle de lésion bilatérale partielle de la substance noire compacte (SNc) ou de l'aire tegmentale ventrale (ATV). L'approche neuroanatomique a permis de montrer que seule la lésion de l'ATV augmente le niveau d'expression des récepteurs D1 au niveau cortical. Nous avons étudié l'effet relatif de ces lésions sur des processus moteurs et cognitifs. Cette étude met en avant une différence entre un "syndrome nigral" (principalement moteur) et un "syndrome tegmental" (essentiellement cognitif).Akinesia is a principal feature of Parkinson's disease. The word akinesia literally means absence of movement. Akinetic symptom in depression and schizophrenia embodies the hypothesis that akinesia involves more than only motor behaviour. Moreover, these disorders have all been associated with evidence of dopamine disrupted homeostasis in the central nervous system. We intended to relate the respective involvement of the nigrostriatal and mesocortical pathways to akinesia. We used a partial bilateral lesioned model of the substania nigra pars compacta (SNc) or ventral tegmental area (VTA). Neuroanatomical study showed that only VTA lesions increased the level of D1 binding in cortical areas. In a second step, we studied the relative effect of lesions on motor and basic cognitive processing. This study highlighted the difference between a "nigral syndrome" (mainly motor) and a "tegmental syndrome" mainly cognitive).BORDEAUX2-BU Santé (330632101) / SudocSudocFranceF

Why bother using non-human primate models of cognitive disorders in translational research?

International audienceAlthough everyone would agree that successful translation of therapeutic candidates for central nervous disorders should involve non-human primate (nhp) models of cognitive disorders, we are left with the paucity of publications reporting either the target validation or the actual preclinical testing in heuristic nhp models. In this review, we discuss the importance of nhps in translational research, highlighting the advances in technological/methodological approaches for 'bridging the gap' between preclinical and clinical experiments. In this process, we acknowledge that nhps remain a vital tool for the investigation of complex cognitive functions, given their resemblance to humans in aspects of behaviour, anatomy and physiology. The recent improvements made for a suitable nhp model in cognitive research, including new surrogates of disease and application of innovative methodological approaches, are continuous strides for reaching efficient translation for human benefit. This will ultimately aid the development of innovative treatments against the current and future threat of neurological and psychiatric disorders to the global population

Levodopa improves motor deficits but can further disrupt cognition in a macaque parkinson model

International audienceBACKGROUND:Levodopa effectively relieves motor symptoms in Parkinson's disease (PD), but has had inconsistent effects on cognition, even worsening some aspects of cognitive functioning. Therefore, remediation of PD cognitive deficits is a major unmet need. However, drug development efforts have been hampered by lack of an animal model in which motor and cognitive deficits can be examined simultaneously.METHODS:Cynomolgus monkeys were trained to perform cognitive tasks and then chronically exposed to MPTP to slowly produce cognitive and motor deficits of parkinsonism.RESULTS:Administration of L-dopa to these animals dose dependently improved motor functioning, but did not significantly improve cognitive performance. At doses that maximally improved motor function, additional cognitive deficits were observed. The present model of MPTP-induced parkinsonism recapitulates important motor and cognitive aspects of PD. Results with L-dopa mirror data derived from PD patients.CONCLUSION:This model should allow more efficient testing of potential PD therapeutics to evaluate motor and cognitive functions simultaneously. © 2012 Movement Disorder Society

Effects of memantine and galantamine on cognitive performance in aged rhesus macaques.

International audienceCurrent pharmacotherapies for Alzheimer's disease (AD) are focused on improving performance of daily activities, personal care, and management of problematic behaviors. Both memantine, a noncompetitive N-methyl-D-aspartate channel blocker and galantamine, a selective acetylcholinesterase inhibitor, are currently prescribed as symptomatic therapies for AD. However, drugs that progressed directly from testing in rodent models to testing in AD patients in clinical trials failed to demonstrate consistent effects on cognitive symptoms. Considering the lack of nonhuman primate data on the effects of memantine and galantamine alone or in combination on cognitive dysfunction in aged nonhuman primates, the present study examined how closely data derived from aged nonhuman primates reflects data obtained in humans. Mild beneficial effects on aspects of cognitive performance in aged primates were found, in general agreement with the human clinical experience with these drugs but in contrast to the more positive effects reported in the rodent literature. These data suggest that the nonhuman primate might have more predictive validity for drug development in this area than comparable rodent assays

Anti-dyskinetic effect of anpirtoline in animal models of L-DOPA-induced dyskinesia

International audienceThe serotonin system has emerged as a potential target for anti-dyskinetic therapy in Parkinson's disease. In fact, serotonin neurons can convert L-DOPA into dopamine, and mediate its synaptic release. However, they lack a feedback control mechanism able to regulate synaptic dopamine levels, which leads to un-physiological stimulation of post-synaptic striatal dopamine receptors. Accordingly, drugs able to dampen the activity of serotonin neurons can suppress L-DOPA-induced dyskinesia in animal models of Parkinson's disease. Here, we investigated the ability of the 5-HT1A/1B receptor agonist anpirtoline to counteract L-DOPA-induced dyskinesia in L-DOPA-primed 6-OHDA-lesioned rats and MPTP-treated macaques. Results suggest that anpirtoline dose-dependently reduced dyskinesia both in rats and monkeys; however, the effect in MPTP-treated macaques was accompanied by a worsening of the Parkinson's disease score at significantly effective doses (1.5 and 2.0mg/kg). At a lower dose (0.75mg/kg), anpirtoline markedly reduced dyskinesia in 4 out of 5 subjects, but statistical significance was prevented by the presence of a non-responsive subject. These results provide further evidence that the serotonin neurons contribute both to the pro-dyskinetic effect of L-DOPA and to its therapeutic efficacy in the rat and monkey models of Parkinson's disease

The mGluR5 negative allosteric modulator dipraglurant reduces dyskinesia in the MPTP macaque model

International audienceBACKGROUND:Blocking metabotropic glutamate receptor type 5 (mGluR5) has been proposed as a target for levodopa-induced dyskinesias (LID) in Parkinson's disease (PD). We assessed the effect on LID of dipraglurant, a potent selective mGluR5 receptor negative allosteric modulator in the gold-standard LID macaque model.METHODS:Dipraglurant (3, 10, and 30 mg/kg, by mouth) was tested in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) macaque model of LID in a four-way crossover, single-dose, controlled study (n = 8).RESULTS:Dipraglurant inhibited dyskinesias in the LID macaque model, with best effect reached at 30 mg/kg dose with no alteration of levodopa efficacy.CONCLUSION:Acute challenges of dipraglurant were efficacious on choreic and dystonic LID in the MPTP-macaque model. Dipraglurant pharmacokinetic variables were similar to those of levodopa, suggesting that both drugs can be co-administered simultaneously in further studies

Engrailed‐1 induces long‐lasting behavior benefit in an experimental Parkinson primate model

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Vector-mediated L-3,4-dihydroxyphenylalanine delivery reverses motor impairments in a primate model of Parkinson's disease

Ever since its introduction 40 years ago l-3,4-dihydroxyphenylalanine (l-DOPA) therapy has retained its role as the leading standard medication for patients with Parkinson's disease. With time, however, the shortcomings of oral l-DOPA treatment have become apparent, particularly the motor fluctuations and troublesome dyskinetic side effects. These side effects, which are caused by the excessive swings in striatal dopamine caused by intermittent oral delivery, can be avoided by delivering l-DOPA in a more continuous manner. Local gene delivery of the l-DOPA synthesizing enzymes, tyrosine hydroxylase and guanosine-tri-phosphate-cyclohydrolase-1, offers a new approach to a more refined dopaminergic therapy where l-DOPA is delivered continuously at the site where it is needed i.e. the striatum. In this study we have explored the therapeutic efficacy of adeno-associated viral vector-mediated l-DOPA delivery to the putamen in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated rhesus monkeys, the standard non-human primate model of Parkinson's disease. Viral vector delivery of the two enzymes, tyrosine hydroxylase and guanosine-5'-tri-phosphate-cyclohydrolase-1, bilaterally into the dopamine-depleted putamen, induced a significant, dose-dependent improvement of motor behaviour up to a level identical to that obtained with the optimal dose of peripheral l-DOPA. Importantly, this improvement in motor function was obtained without any adverse dyskinetic effects. These results provide proof-of-principle for continuous vector-mediated l-DOPA synthesis as a novel therapeutic strategy for Parkinson's disease. The constant, local supply of l-DOPA obtained with this approach holds promise as an efficient one-time treatment that can provide long-lasting clinical improvement and at the same time prevent the appearance of motor fluctuations and dyskinetic side effects associated with standard oral dopaminergic medication.status: publishe