Polymeric IgA is superior to monomeric IgA and IgG carrying the same variable domain in preventing Clostridium difficile toxin A damaging of T84 monolayers.

The two exotoxins A and B produced by Clostridium difficile are responsible for antibiotic-associated enterocolitis in human and animals. When added apically to human colonic carcinoma-derived T84 cell monolayers, toxin A, but not toxin B, abolished the transepithelial electrical resistance and altered the morphological integrity. Apical addition of suboptimal concentration of toxin A made the cell monolayer sensitive to toxin B. Both toxins induced drastic and rapid epithelial alterations when applied basolaterally with a complete disorganization of tight junctions and vacuolization of the cells. Toxin A-specific IgG2a from hybridoma PCG-4 added apically with toxin A alone or in combination with toxin B abolished the toxin-induced epithelial alterations for up to 8 h. The Ab neutralized basolateral toxin A for 4 h, but not the mixture of the two toxins. Using an identical Ab:Ag ratio, we found that recombinant polymeric IgA (IgAd/p) with the same Fv fragments extended protection against toxin A for at least 24 h in both compartments. In contrast, the recombinant monomeric IgA counterpart behaved as the PCG-4 IgG2a Ab. The direct comparison between different Ig isotype and molecular forms, but of unique specificity, demonstrates that IgAd/p Ab is more efficient in neutralizing toxin A than monomeric IgG and IgA. We conclude that immune protection against C. difficile toxins requires toxin A-specific secretory Abs in the intestinal lumen and IgAd/p specific for both toxins in the lamina propria.

Repeating with the right hemisphere: reduced interactions between phonological and lexical-semantic systems in crossed aphasia?

Knowledge on the patterns of repetition amongst individuals who develop language deficits in association with right hemisphere lesions (crossed aphasia) is very limited. Available data indicate that repetition in some crossed aphasics experiencing phonological processing deficits is not heavily influenced by lexical-semantic variables (lexicality, imageability, and frequency) as is regularly reported in phonologically-impaired cases with left hemisphere damage. Moreover, in view of the fact that crossed aphasia is rare, information on the role of right cortical areas and white matter tracts underpinning language repetition deficits is scarce. In this study, repetition performance was assessed in two patients with crossed conduction aphasia and striatal/capsular vascular lesions encompassing the right arcuate fasciculus (AF) and inferior frontal-occipital fasciculus (IFOF), the temporal stem and the white matter underneath the supramarginal gyrus. Both patients showed lexicality effects repeating better words than non-words, but manipulation of other lexical-semantic variables exerted less influence on repetition performance. Imageability and frequency effects, production of meaning-based paraphrases during sentence repetition, or better performance on repeating novel sentences than overlearned clichés were hardly ever observed in these two patients. In one patient, diffusion tensor imaging disclosed damage to the right long direct segment of the AF and IFOF with relative sparing of the anterior indirect and posterior segments of the AF, together with fully developed left perisylvian white matter pathways. These findings suggest that striatal/capsular lesions extending into the right AF and IFOF in some individuals with right hemisphere language dominance are associated with atypical repetition patterns which might reflect reduced interactions between phonological and lexical-semantic processes.

Intracortical connectivity of layer VI pyramidal neurons in the somatosensory cortex of normal and barrelless mice.

In mice, barrels in layer IV of the somatosensory cortex correspond to the columnar representations of whisker follicles. In barrelless (BRL) mice, barrels are absent, but functionally, a columnar organization persists. Previously we characterized the aberrant geometry of thalamic projection of BRL mice using axonal reconstructions of individual neurons. Here we proceeded with the analysis of the intracortical projections from layer VI pyramidal neurons, to assess their contribution to the columnar organization. From series of tangential sections we reconstructed the axon collaterals of individual layer VI pyramidal neurons in the C2 barrel column that were labelled with biocytin [controls from normal (NOR) strain, 19 cells; BRL strain, nine cells]. Using six morphological parameters in a cluster analysis, we showed that layer VI neurons in NOR mice are distributed into four clusters distinguished by the radial and tangential extent of their intracortical projections. These clusters correlated with the cortical or subcortical projection of the main axon. In BRL mice, neurons were distributed within the same four clusters, but their projections to the granular and supragranular layers were significantly smaller and their tangential projection was less columnar than in NOR mice. However, in both strains the intracortical projections had a preference for the appropriate barrel column (C2), indicating that layer VI pyramidal cells could participate in the functional columnar organization of the barrel cortex. Correlative light and electron microscopy analyses provided morphometric data on the intracortical synaptic boutons and synapses of layer VI pyramidal neurons and revealed that projections to layer IV preferentially target excitatory dendritic spines and shafts.

Alterations in phosphatidylinositol 3-kinase activity and PTEN phosphatase in the prefrontal cortex of depressed suicide victims.

BACKGROUND: Recent studies have reported alterations in protein kinase B (PKB)/Akt and in its downstream target, glycogen synthase kinase 3β, in depression and suicide. The aim of the present study was to investigate possible impairment of the upstream regulators, namely phosphatidylinositol 3-kinase (PI3K) and PTEN. METHODS: The ventral prefrontal cortex (Brodmann's area 11) of 24 suicide victims and 24 drug-free nonsuicide subjects was used. The antemortem diagnoses of major depression disorder were obtained from the institutional records or psychological autopsy, and toxicological analyses were performed. Protein levels of PI3K and PTEN were assayed using the immunoblot method, and the kinase activity of PI3K and Akt was determined by phosphorylation of specific substrates. RESULTS: A decrease was observed in the enzymatic activity of PI3K [ANOVA: F(3, 44) = 9.20; p < 0.001] and Akt1 [ANOVA: F(3, 44) = 13.59; p < 0.001], without any change in protein levels, in both depressed suicide victims and depressed nonsuicide subjects (p < 0.01 and p < 0.002, respectively). PTEN protein levels were increased in the same groups [ANOVA: F(3, 44) = 10.5; p < 0.001]. No change was observed in nondepressed suicide victims. CONCLUSION: This study concludes that attenuation of kinase activity of PKB/Akt in depressed suicide victims may be due to the combined dysregulation of PTEN and PI3K resulting in insufficient phosphorylation of lipid second messengers. The effect is associated with major depression rather than with suicide per se. Given the cellular deficits reported in major depression, the study of enzymes involved in cell survival and neuroplasticity is particularly relevant to neurotrophic factor dysregulation in depression.

Controversies about the enhanced vulnerability of the adolescent brain to develop addiction.

Adolescence, defined as a transition phase toward autonomy and independence, is a natural time of learning and adjustment, particularly in the setting of long-term goals and personal aspirations. It also is a period of heightened sensation seeking, including risk taking and reckless behaviors, which is a major cause of morbidity and mortality among teenagers. Recent observations suggest that a relative immaturity in frontal cortical neural systems may underlie the adolescent propensity for uninhibited risk taking and hazardous behaviors. However, converging preclinical and clinical studies do not support a simple model of frontal cortical immaturity, and there is substantial evidence that adolescents engage in dangerous activities, including drug abuse, despite knowing and understanding the risks involved. Therefore, a current consensus considers that much brain development during adolescence occurs in brain regions and systems that are critically involved in the perception and evaluation of risk and reward, leading to important changes in social and affective processing. Hence, rather than naive, immature and vulnerable, the adolescent brain, particularly the prefrontal cortex, should be considered as prewired for expecting novel experiences. In this perspective, thrill seeking may not represent a danger but rather a window of opportunities permitting the development of cognitive control through multiple experiences. However, if the maturation of brain systems implicated in self-regulation is contextually dependent, it is important to understand which experiences matter most. In particular, it is essential to unveil the underpinning mechanisms by which recurrent adverse episodes of stress or unrestricted access to drugs can shape the adolescent brain and potentially trigger life-long maladaptive responses.

Accidental cross-clamping of the superior vena cava: management and BIS evolution.

The case of a 38-year old man with recurrent adenocarcinoma of the right lung and infiltration of the thoracic wall, who underwent a right pneumonectomy with thoracic wall resection, is described. Dissection of the right pulmonary hilous was extremely difficult due to the previous operations. The superior vena cava (SVC) was accidentally ligated, resulting in profound hypotension and increased venous pressure in the internal jugular vein. Immediate blood aspiration through a 8.5-French introducer sheath lowered the venous congestion. After the SVC was cross-clamped, the Bispectral Index (BIS) acutely decreased to 0 and remained low during the resuscitation. Over the next 5 hours, BIS was directly affected by mean arterial pressure. Four days postoperatively, the patient was neurologically intact.

Universitat i societat xarxa : Usos d'Internet en el sistema educatiu superior de Catalunya. Informe final de recerca (annexos web)

Annexos web de l'estudi que analitza -seguint una metodologia quantitativa basada en una mostra representativa de 2.093 professors i 23.864 estudiants i reforçada amb elements qualitatius- la transició que es produeix en el sistema universitari públic català cap a un model més adaptat a les noves necessitats de la societat xarxa. Per a això, es posa especial èmfasi en l'anàlisi dels usos que es fa d'Internet (l'eina clau de la societat xarxa) en el món universitari i en les transformacions que es donen o es donaran com a conseqüència d'aquests usos.

Universitat i societat xarxa : Usos d'Internet en el sistema educatiu superior de Catalunya. Informe final de recerca (volum I)

Aquest estudi analitza -seguint una metodologia quantitativa basada en una mostra representativa de 2.093 professors i 23.864 estudiants i reforçada amb elements qualitatius- la transició que es produeix en el sistema universitari públic català cap a un model més adaptat a les noves necessitats de la societat xarxa. Per a això, es posa especial èmfasi en l'anàlisi dels usos que es fa d'Internet (l'eina clau de la societat xarxa) en el món universitari i en les transformacions que es donen o es donaran com a conseqüència d'aquests usos.

Universitat i societat xarxa : Usos d'Internet en el sistema educatiu superior de Catalunya. Informe final de recerca (volum II)

Aquest estudi analitza -seguint una metodologia quantitativa basada en una mostra representativa de 2.093 professors i 23.864 estudiants i reforçada amb elements qualitatius- la transició que es produeix en el sistema universitari públic català cap a un model més adaptat a les noves necessitats de la societat xarxa. Per a això, es posa especial èmfasi en l'anàlisi dels usos que es fa d'Internet (l'eina clau de la societat xarxa) en el món universitari i en les transformacions que es donen o es donaran com a conseqüència d'aquests usos.

Measuring sustained superior performance at the firm level

This paper proposes a two-dimensional Strategic Performance Measure (SPM) to evaluate the achievement of sustained superior performance. This proposal builds primarily on the fact that, under the strategic management perspective, a firm's prevalent objective is the pursuit of sustained superior performance. Three basicconceptual dimensions stem from this objective: relativity, sign dependence, and dynamism. These are the foundations of the SPM, which carries out a separate evaluation of the attained superior performance and of its sustainability over time. In contrast to existing measures of performance, the SPM provides: (i) a dynamic approach by considering the progress or regress in performance over time, and (ii) a cardinal measurement of performance differences and its changes over time. The paper also proposes an axiomatic framework that ameasure of strategic performance should comply with to be theoretically and managerially sound. Finally, anempirical illustration of the Spanish banking sector during 1987-1999 is herein provided by discussing some relevant case

The neurobiological basis of prefrontal cortex impairment in the phencyclidine model of schizophrenia : convergent reduction of synaptic glutamate release, energy metabolism and cognitive performance

RÉSUMÉ : Le traitement répété à la phencyclidine (PCP), un bloqueur du récepteur NMDA (NMDAR), reproduit chez les rongeurs une partie de la symptomatologie typique de la schizophrénie. Le blocage prolongé du NMDAR par la PCP mime une hypofunction du NMDAR, une des principales altérations supposées exister dans les cerveaux des patients schizophréniques. Le but de notre étude était d'examiner les conséquences neurochimiques, métaboliques et fonctionnelles du traitement répété à la phencyclidine in vivo, au niveau du cortex préfrontal (cpf), une région cérébrale qui joue un rôle dans les déficits cognitifs observés chez les patients schizophréniques. Pour répondre à cette question, les rats ou les souris ont reçu chaque jour une injection soit de PCP (5 mg/kg), soit de solution saline, pendant 7 ou 14 jours. Les animaux ont ensuite été sacrifiés au moins 24 heures après le dernier traitement. Des tranches aiguës du cpf ont été préparées rapidement, puis stimulées avec une concentration élevée de KCI, de manière à induire une libération de glutamate à partir des terminaisons synaptiques excitatrices. Les résultats montrent que les tranches du cpf des animaux traités à la PCP ont libéré une quantité de glutamate significativement inférieure par rapport à celles des animaux contrôle. Ce déficit de libération a persisté 72 heures après la fin du traitement, tandis qu'il n'était pas observé dans le cortex visuel primaire, une autre région corticale. En outre, le traitement avec des antipsychotiques, l'halopéridol ou l'olanzapine, a supprimé le déficit induit par la PCP. Le même déficit de libération a été remarqué sur des synaptosomes obtenus à partir du cpf des animaux traités à la phenryclidine. Cette observation indique que la PCP induit une modification plastique adaptative du mécanisme qui contrôle la libération du glutamate dans les terminaisons synaptiques. Nous avons découvert que cette modification implique la sous-régulation d'un NMDAR présynaptique, qui serait doué d'un rôle d'autorécepteur stimulateur de la libération du glutamate. Grâce à des tests comportementaux conduits en parallèle et réalisés pour évaluer la fonctionnalité du cpf, nous avons observé chez les souris traitées à la PCP une flexibilité comportementale réduite lors d'un test de discrimination de stimuli visuels/tactiles. Le déficit cognitif était encore présent 4 jours après la dernière administration de PCP. La technique de l'autoradiographie quantitative du [14C]2-deoxyglucose a permis d'associer ce déficit à une réduction de l'activité métabolique cérébrale pendant le déroulement du test, particulièrement au niveau du cpf. Dans l'ensemble, nos résultats suggèrent que le blocage prolongé du NMDAR lors de l'administration répétée de PCP produit un déficit de libération du glutamate au niveau des terminaisons synaptiques excitatrices du cpf. Un tel déficit pourrait être provoqué par la sousrégulation d'un NMDAR présynaptique, qui aurait une fonction de stimulateur de libération; la transmission excitatrice du cpf s'en trouverait dans ce cas réduite. Ce résultat est en ligne avec l'activité métabolique et fonctionnelle réduite du cpf et l'observation de déficits cognitifs induits lors de l'administration de la PCP. ABSTRACT : Sub-chronic treatment with phencyclidine (PCP), an NMDA receptor (NMDAR) channel blocker, reproduces in rodents part of the symptomatology associated to schizophrenia in humans. Prolonged pharmacological blockade of NMDAR with PCP mimics NMDAR hypofunction, one of the main alterations thought to take place in the brains of schizophrenics. Our study was aimed at investigating the neurochemical, metabolic and behavioral consequences of repeated PCP administration in vivo, focusing on the functioning of the prefrontal cortex (pfc), a brain region highly relevant for the cognitive deficits observed in schizophrenic patients. Rats or mice received a daily administration of either PCP (5 mg/kg) or saline for 7 or 14 days. At least 24 hours after the last treatment the animals were sacrificed. Acute slices of the pfc were quickly prepared and challenged with high KCl to induce synaptic glutamate release. Pfc slices from PCP-treated animals released significantly less glutamate than slices from salinetreated animals. The deficit persisted 72 hours after the end of the treatment, while it was not observed in another cortical region: the primary visual cortex. Interestingly, treatment with antipsychotic drugs, either haloperidol or olanzapine, reverted the glutamate release defect induced by PCP treatment. The same release defect was observed in synaptosomes prepared from the pfc of PCP-treated animals, indicating that PCP induces a plastic adaptive change in the mechanism controlling glutamate release in the glutamatergic terminals. We discovered that such change most likely involves the down-regulation of a newly identified, pre-synaptic NMDAR with stimulatory auto-receptor function on glutamate release. In parallel sets of behavioral experiments challenging pfc function, mice sub-chronically treated with PCP displayed reduced behavioral flexibility (reversal learning) in a visual/tactile-cued discrimination task. The cognitive deficit was still evident 4 days after the last PCP administration and was associated to reduced brain metabolic activity during the performance of the behavioral task, notably in the pfc, as determined by [14C]2-deoxyglucose quantitative autoradiography. Clverall, our findings suggest that prolonged NMDAR blockade by repeated PCP administration results in a defect of glutamate release from excitatory afferents in the pfc, possibly ascribed to down-regulation of apre-synaptic stimulatory NMDAR. Deficient excitatory neurotransmission in the pfc is consistent with the reduced metabolic and functional activation of this area and the observed PCP-induced cognitive deficits.

Thorax, pelvis and hip pattern in the frontal plane during walking in unilateral transtibial amputees: biomechanical analysis.

BACKGROUND Lower limb amputees exhibit postural control deficits during standing which can affect their walking ability. OBJECTIVES The primary purpose of the present study was to analyze the thorax, pelvis, and hip kinematics and the hip internal moment in the frontal plane during gait in subjects with Unilateral Transtibial Amputation (UTA). METHOD The participants included 25 people with UTA and 25 non-amputees as control subjects. Gait analysis was performed using the Vicon(r) Motion System. We analyzed the motion of the thorax, pelvis, and hip (kinematics) as well as the hip internal moment in the frontal plane. RESULTS The second peak of the hip abductor moment was significantly lower on the prosthetic side than on the sound side (p=.01) and the control side (right: p=.01; left: p=.01). During middle stance, the opposite side of the pelvis was higher on the prosthetic side compared to the control side (right: p=.01: left: p=.01). CONCLUSIONS The joint internal moment at the hip in the frontal plane was lower on the prosthetic side than on the sound side or the control side. Thorax and pelvis kinematics were altered during the stance phase on the prosthetic side, presumably because there are mechanisms which affect postural control during walking.

Net increase of lactate and glutamate concentration in activated human visual cortex detected with magnetic resonance spectroscopy at 7 tesla.

After the landmark studies reporting changes in the cerebral metabolic rate of glucose (CMRGlc ) in excess of those in oxygen (CMRO2 ) during physiological stimulation, several studies have examined the fate of the extra carbon taken up by the brain, reporting a wide range of changes in brain lactate from 20% to 250%. The present study reports functional magnetic resonance spectroscopy measurements at 7 Tesla using the enhanced sensitivity to study a small cohort (n = 6). Small increases in lactate (19% ± 4%, P < 0.05) and glutamate (4% ± 1%, P < 0.001) were seen within the first 2 min of activation. With the exception of glucose (12% ± 5%, P < 0.001), no other metabolite concentration changes beyond experimental error were significantly observed. Therefore, the present study confirms that lactate and glutamate changes during physiological stimulation are small (i.e. below 20%) and shows that the increased sensitivity allows reproduction of previous results with fewer subjects. In addition, the initial rate of glutamate and lactate concentration increases implies an increase in CMRO2 that is slightly below that of CMRGlc during the first 1-2 min of activation.

Functional MRI Mapping of the Human Auditory Cortex

Mapping the human auditory cortex with standard functional imaging techniques is difficult because of its small size and angular position along the Sylvian fissure. As a result, the exact number and location of auditory cortex areas in the human remains unknown. In a first experiment, we measured the two largest tonotopic areas of primary auditory cortex (PAC, Al and R) using high-resolution functional MRI at 7 Tesla relative to the underlying anatomy of Heschl's gyrus (HG). The data reveals a clear anatomical- functional relationship that indicates the location of PAC across the range of common morphological variants of HG (single gyri, partial duplication and complete duplication). Human PAC tonotopic areas are oriented along an oblique posterior-to-anterior axis with mirror-symmetric frequency gradients perpendicular to HG, as in the macaque. In a second experiment, we tested whether these primary frequency-tuned units were modulated by selective attention to preferred vs. non-preferred sound frequencies in the dynamic manner needed to account for human listening abilities in noisy environments, such as cocktail parties or busy streets. We used a dual-stream selective attention experiment where subjects attended to one of two competing tonal streams presented simultaneously to different ears. Attention to low-frequency tones (250 Hz) enhanced neural responses within low-frequency-tuned voxels relative to high (4000 Hz), and vice versa when at-tention switched from high to low. Human PAC is able to tune into attended frequency channels and can switch frequencies on demand, like a radio. In a third experiment, we investigated repetition suppression effects to environmental sounds within primary and non-primary early-stage auditory areas, identified with the tonotopic mapping design. Repeated presentations of sounds from the same sources, as compared to different sources, gave repetition suppression effects within posterior and medial non-primary areas of the right hemisphere, reflecting their potential involvement in semantic representations. These three studies were conducted at 7 Tesla with high-resolution imaging. However, 7 Tesla scanners are, for the moment, not yet used for clinical diagnosis and mostly reside in institutions external to hospitals. Thus, hospital-based clinical functional and structural studies are mainly performed using lower field systems (1.5 or 3 Tesla). In a fourth experiment, we acquired tonotopic maps at 3 and 7 Tesla and evaluated the consistency of a tonotopic mapping paradigm between scanners. Mirror-symmetric gradients within PAC were highly similar at 7 and 3 Tesla across renderings at different spatial resolutions. We concluded that the tonotopic mapping paradigm is robust and suitable for definition of primary tonotopic areas, also at 3 Tesla. Finally, in a fifth study, we considered whether focal brain lesions alter tonotopic representations in the intact ipsi- and contralesional primary auditory cortex in three patients with hemispheric or cerebellar lesions, without and with auditory complaints. We found evidence for tonotopic reorganisation at the level of the primary auditory cortex in cases of brain lesions independently of auditory complaints. Overall, these results reflect a certain degree of plasticity within primary auditory cortex in different populations of subjects, assessed at different field strengths. - La cartographie du cortex auditif chez l'humain est difficile à réaliser avec des techniques d'imagerie fonctionnelle standard, étant donné sa petite taille et position angulaire le long de la fissure sylvienne. En conséquence, le nombre et l'emplacement exacts des différentes aires du cortex auditif restent inconnus chez l'homme. Lors d'une première expérience, nous avons mesuré, avec de l'imagerie par résonance magnétique à haute intensité (IRMf à 7 Tesla) chez des sujets humains sains, deux larges aires au sein du cortex auditif primaire (PAC; Al et R) avec une représentation spécifique des fréquences pures préférées - ou tonotopie. Nos résultats ont démontré une relation anatomico- fonctionnelle qui définit clairement la position du PAC à travers toutes les variantes du gyrus d'Heschl's (HG). Les aires tonotopiques du PAC humain sont orientées le long d'un axe postéro-antérieur oblique avec des gradients de fréquences spécifiques perpendiculaires à HG, d'une manière similaire à celles mesurées chez le singe. Dans une deuxième expérience, nous avons testé si ces aires primaires pouvaient être modulées, de façon dynamique, par une attention sélective pour des fréquences préférées par rapport à celles non-préférées. Cette modulation est primordiale lors d'interactions sociales chez l'humain en présence de bruits distracteurs tels que d'autres discussions ou un environnement sonore nuisible (comme par exemple, dans la circulation routière). Dans cette étude, nous avons utilisé une expérience d'attention sélective où le sujet devait être attentif à une des deux voies sonores présentées simultanément à chaque oreille. Lorsque le sujet portait était attentif aux sons de basses fréquences (250 Hz), la réponse neuronale relative à ces fréquences augmentait par rapport à celle des hautes fréquences (4000 Hz), et vice versa lorsque l'attention passait des hautes aux basses fréquences. De ce fait, nous pouvons dire que PAC est capable de focaliser sur la fréquence attendue et de changer de canal selon la demande, comme une radio. Lors d'une troisième expérience, nous avons étudié les effets de suppression due à la répétition de sons environnementaux dans les aires auditives primaires et non-primaires, d'abord identifiées via le protocole de la première étude. La présentation répétée de sons provenant de la même source sonore, par rapport à de sons de différentes sources sonores, a induit un effet de suppression dans les aires postérieures et médiales auditives non-primaires de l'hémisphère droite, reflétant une implication de ces aires dans la représentation de la catégorie sémantique. Ces trois études ont été réalisées avec de l'imagerie à haute résolution à 7 Tesla. Cependant, les scanners 7 Tesla ne sont pour le moment utilisés que pour de la recherche fondamentale, principalement dans des institutions externes, parfois proches du patient mais pas directement à son chevet. L'imagerie fonctionnelle et structurelle clinique se fait actuellement principalement avec des infrastructures cliniques à 1.5 ou 3 Tesla. Dans le cadre dune quatrième expérience, nous avons avons évalués la cohérence du paradigme de cartographie tonotopique à travers différents scanners (3 et 7 Tesla) chez les mêmes sujets. Nos résultats démontrent des gradients de fréquences définissant PAC très similaires à 3 et 7 Tesla. De ce fait, notre paradigme de définition des aires primaires auditives est robuste et applicable cliniquement. Finalement, nous avons évalués l'impact de lésions focales sur les représentations tonotopiques des aires auditives primaires des hémisphères intactes contralésionales et ipsilésionales chez trois patients avec des lésions hémisphériques ou cérébélleuses avec ou sans plaintes auditives. Nous avons trouvé l'évidence d'une certaine réorganisation des représentations topographiques au niveau de PAC dans le cas de lésions cérébrales indépendamment des plaintes auditives. En conclusion, nos résultats démontrent une certaine plasticité du cortex auditif primaire avec différentes populations de sujets et différents champs magnétiques.

Tau hyperphosphorylation and increased BACE1 and RAGE levels in the cortex of PPARβ/δ-null mice.

The role of peroxisome proliferator activator receptor (PPAR)β/δ in the pathogenesis of Alzheimer's disease has only recently been explored through the use of PPARβ/δ agonists. Here we evaluated the effects of PPARβ/δ deficiency on the amyloidogenic pathway and tau hyperphosphorylation. PPARβ/δ-null mice showed cognitive impairment in the object recognition task, accompanied by enhanced DNA-binding activity of NF-κB in the cortex and increased expression of IL-6. In addition, two NF-κB-target genes involved in β-amyloid (Aβ) synthesis and deposition, the β site APP cleaving enzyme 1 (Bace1) and the receptor for advanced glycation endproducts (Rage), respectively, increased in PPARβ/δ-null mice compared to wild type animals. The protein levels of glial fibrillary acidic protein (GFAP) increased in the cortex of PPARβ/δ-null mice, which would suggest the presence of astrogliosis. Finally, tau hyperphosphorylation at Ser199 and enhanced levels of PHF-tau were associated with increased levels of the tau kinases CDK5 and phospho-ERK1/2 in the cortex of PPARβ/δ(-/-) mice. Collectively, our findings indicate that PPARβ/δ deficiency results in cognitive impairment associated with enhanced inflammation, astrogliosis and tau hyperphosphorylation in the cortex.