VEGF-D Downregulation in CA1 Pyramidal Neurons Exerts Asymmetric Changes of Dendritic Morphology without Correlated Electrophysiological Alterations.

The morphology of dendritic arbors determines the location, strength and interaction of synaptic inputs. It is therefore important to understand the factors regulating dendritic arborization both during development and in situations of physiological or pathological plasticity. We have recently shown that VEGF-D (Vascular Endothelial Growth Factor D) is required to maintain length and complexity of basal dendrites in mouse hippocampal pyramidal cells. Lack of VEGF-D resulted in long-term memory deficits, suggesting a link between dendritic morphology and cognitive function. Here, we compared the effect of VEGF-D expression on basal versus apical dendrites of CA1 pyramidal cells, as well as its importance for synaptic processing of network oscillations. We report opposing, layer-specific effects of VEGF-D knockdown which resulted in shrinkage of basal and increased complexity of apical dendrites. Synaptic potentials and layer-specific voltage gradients during network oscillations remained, however, unaltered. These findings reveal a high spatial selectivity of VEGF-D effects at the sub-cellular level, and strong homeostatic mechanisms which keep spatially segregated synaptic inputs in a balance.

Prolonged quiescence delays somatic stem cell-like divisions in Caenorhabditis elegans and is controlled by insulin signaling.

Cells can enter quiescence in adverse conditions and resume proliferation when the environment becomes favorable. Prolonged quiescence comes with a cost, reducing the subsequent speed and potential to return to proliferation. Here, we show that a similar process happens during Caenorhabditis elegans development, providing an in vivo model to study proliferative capacity after quiescence. Hatching under starvation provokes the arrest of blast cell divisions that normally take place during the first larval stage (L1). We have used a novel method to precisely quantify each stage of postembryonic development to analyze the consequences of prolonged L1 quiescence. We report that prolonged L1 quiescence delays the reactivation of blast cell divisions in C. elegans, leading to a delay in the initiation of postembryonic development. The transcription factor DAF-16/FOXO is necessary for rapid recovery after extended arrest, and this effect is independent from its role as a suppressor of cell proliferation. Instead, the activation of DAF-16 by decreased insulin signaling reduces the rate of L1 aging, increasing proliferative potential. We also show that yolk provisioning affects the proliferative potential after L1 arrest modulating the rate of L1 aging, providing a possible mechanistic link between insulin signaling and the maintenance of proliferative potential. Furthermore, variable yolk provisioning in embryos is one of the sources of interindividual variability in recovery after quiescence of genetically identical animals. Our results support the relevance of L1 arrest as an in vivo model to study stem cell-like aging and the mechanisms for maintenance of proliferation potential after quiescence.

Synaptic entrainment of ectopic action potential generation in hippocampal pyramidal neurons.

KEY POINTS: Ectopic action potentials (EAPs) arise at distal locations in axonal fibres and are often associated with neuronal pathologies such as epilepsy or nerve injury, but they also occur during physiological network conditions. This study investigates whether initiation of such EAPs is modulated by subthreshold synaptic activity. Somatic subthreshold potentials invade the axonal compartment to considerable distances (>350 µm), whereas spread of axonal subthreshold potentials to the soma is inefficient. Ectopic spike generation is entrained by conventional synaptic signalling mechanisms. Excitatory synaptic potentials promote EAPs, whereas inhibitory synaptic potentials block EAPs. The modulation of ectopic excitability depends on propagation of somatic voltage deflections to the axonal EAP initiation site. Synaptic modulation of EAP initiation challenges the view of the distal axon being independent of synaptic activity and may contribute to mechanisms underlying fast network oscillations and pathological network activity. ABSTRACT: While most action potentials are generated at the axon initial segment, they can also be triggered at more distal sites along the axon. Such ectopic action potentials (EAPs) occur during several neuronal pathologies such as epilepsy, nerve injuries and inflammation but have also been observed during physiological network activity. EAPs propagate antidromically towards the somato-dendritic compartment where they modulate synaptic plasticity. Here we investigate the converse signal direction: do somato-dendritic synaptic potentials affect the generation of ectopic spikes? We measured anti- and orthodromic spikes in the soma and axon of mouse hippocampal CA1 pyramidal cells. We found that synaptic potentials propagate reliably through the axon, causing significant voltage transients at distances >350 µm. At these sites, excitatory input efficiently facilitated EAP initiation in distal axons and, conversely, inhibitory input suppressed EAP initiation. Our data reveal a new mechanism by which ectopically generated spikes can be entrained by conventional synaptic signalling during normal and pathological network activity.

How does family intervention improve the outcome of people with schizophrenia?

BACKGROUND: There is strong evidence of the efficacy of family psychosocial interventions for schizophrenia, but evidence of the role played by the attitudes of relatives in the therapeutic process is lacking. METHOD: To study the effect of a family intervention on family attitudes and to analyse their mediating role in the therapeutic process 50 patients with schizophrenia and their key relatives undergoing a trial on the efficacy of a family psychosocial intervention were studied by means of the Affective Style Coding System, the Scale of Empathy, and the Relational Control Coding System. Specific statistical methods were used to determine the nature of the relationship of the relatives' attitudes to the outcome of family intervention. RESULTS: Family psychosocial intervention was associated with a reduction in relatives' guilt induction and dominance and an improvement in empathy. Empathy and lack of dominance were identified as independent mediators of the effect of family psychosocial intervention. The change in empathy and dominance during the first 9 months of the intervention predicted the outcome in the following 15 months. CONCLUSION: Relatives' empathy and lack of dominance are mediators of the beneficial effect of family psychosocial intervention on patient's outcome.

Axon-carrying dendrites convey privileged synaptic input in hippocampal neurons.

Neuronal processing is classically conceptualized as dendritic input, somatic integration, and axonal output. The axon initial segment, the proposed site of action potential generation, usually emanates directly from the soma. However, we found that axons of hippocampal pyramidal cells frequently derive from a basal dendrite rather than from the soma. This morphology is particularly enriched in central CA1, the principal hippocampal output area. Multiphoton glutamate uncaging revealed that input onto the axon-carrying dendrites (AcDs) was more efficient in eliciting action potential output than input onto regular basal dendrites. First, synaptic input onto AcDs generates action potentials with lower activation thresholds compared with regular dendrites. Second, AcDs are intrinsically more excitable, generating dendritic spikes with higher probability and greater strength. Thus, axon-carrying dendrites constitute a privileged channel for excitatory synaptic input in a subset of cortical pyramidal cells.

Animal model of Mycoplasma fermentans respiratory infection.

BACKGROUND: Mycoplasma fermentans has been associated with respiratory, genitourinary tract infections and rheumatoid diseases but its role as pathogen is controversial. The purpose of this study was to probe that Mycoplasma fermentans is able to produce respiratory tract infection and migrate to several organs on an experimental infection model in hamsters. One hundred and twenty six hamsters were divided in six groups (A-F) of 21 hamsters each. Animals of groups A, B, C were intratracheally injected with one of the mycoplasma strains: Mycoplasma fermentans P 140 (wild strain), Mycoplasma fermentans PG 18 (type strain) or Mycoplasma pneumoniae Eaton strain. Groups D, E, F were the negative, media, and sham controls. Fragments of trachea, lungs, kidney, heart, brain and spleen were cultured and used for the histopathological study. U frequency test was used to compare recovery of mycoplasmas from organs. RESULTS: Mycoplasmas were detected by culture and PCR. The three mycoplasma strains induced an interstitial pneumonia; they also migrated to several organs and persisted there for at least 50 days. Mycoplasma fermentans P 140 induced a more severe damage in lungs than Mycoplasma fermentans PG 18. Mycoplasma pneumoniae produced severe damage in lungs and renal damage. CONCLUSIONS: Mycoplasma fermentans induced a respiratory tract infection and persisted in different organs for several weeks in hamsters. This finding may help to explain the ability of Mycoplasma fermentans to induce pneumonia and chronic infectious diseases in humans.

Prevalencia, características electrocardiográficas y localización de las vías accesorias en el Wolff-Parkinson-White sobre una población de 24.000 individuos aparentemente sanos / Prevalence, Electrocardiographic characteristics and localization of accesory connections of the wolff-Parkinson-White syndrome in a population of 24.000 apparently healthy subjects

El síndrome de preexcitación tiene una larga e interesante historia, esta anormalidad electrocardiográfica fue descripta por Wolff-Parkinson-White y una conexión AV accesoria resulta ser su sustrato anatómico. Sin embargo, aun después de la documentación de estas vías accesorias, la búsqueda de mecanismos alternativos para explicar la preexcitación continuó. Finalmente, el estudio electrofisiológico y la terapia quirúrgica o ablativa confirmó la teoría. Las distintas publicaciones hacen referencia a disímiles frecuencias de presentación, dependiendo particularmente de la población de estudio.

Experimental arthritis induced by a clinical Mycoplasma fermentans isolate.

BACKGROUND: Mycoplasma fermentans has been associated with rheumatoid arthritis. Recently, it was detected in the joints and blood of patients with rheumatoid arthritis, but it is not clear yet how the bacteria enter the body and reach the joints. The purpose of this study was to determine the ability of M. fermentans to induce experimental arthritis in rabbits following inoculation of the bacteria in the trachea and knee joints. METHODS: P-140 and PG-18 strains were each injected in the knee joints of 14 rabbits in order to evaluate and compare their arthritogenicity. P-140 was also injected in the trachea of 14 rabbits in order to test the ability of the bacteria to reach the joints and induce arthritis. RESULTS: M. fermentans produced an acute arthritis in rabbits. Joint swelling appeared first in rabbits injected with P-140, which caused a more severe arthritis than PG-18. Both strains were able to migrate to the uninoculated knee joints and they were detected viable in the joints all along the duration of the experiment. Changes in the synovial tissue were more severe by the end of the experiment and characterized by the infiltration of neutrophils and substitution of adipose tissue by connective tissue. Rabbits intracheally injected with P-140 showed induced arthritis and the bacteria could be isolated from lungs, blood, heart, kidney, spleen, brain and joints. CONCLUSION: M. fermentans induced arthritis regardless of the inoculation route. These findings may help explain why mycoplasmas are commonly isolated from the joints of rheumatic patients.

Detection of mycoplasma hominis and ureaplasma urealyticum in women sexually active or not

Los micoplasmas genitales juegan un papel importante en las infecciones del aparato genitourinario, por lo que su estudio es de gran importancia. El objetivo del presente trabajo fue aislar Mycoplasma hominis y Ureaplasma urealyticum a partir de exudados vaginales, faríngeos y de orina de personas con y sin actividad sexual. Se tomaron muestras de mujeres sin infección del aparato genitourinario (testigos) y con infección (problemas) y fueron depositadas en un mililitro de caldo E con arginina o urea y a partir de ellas se realizaron diluciones decimales (10-1 a 10-10) y se incubaron a 37ºC hasta vire del indicador. La identificación de especie se realizó con la técnica de polimerización en cadena utilizando oligonucleótidos específicos para M. hominis que corresponden al gen del RNAr 16S y oligonucleótidos específicos para U. urealyticum que corresponden al gen estructural de la ureasa, la técnica fue realizada de acuerdo con Blanchard et al. No hubo diferencias significativas (X² P > .05), en los porcentajes de aislamiento de estos microorganismos a partir de exudados vaginales, pero sí hubo a partir de muestras de orina. Estos micoplasmas fueron aislados en altos porcentajes de mujeres adolescentes y fueron recuperados hasta la quinta dilución decimal. A partir de exudados faríngeos sólo fueron aislados de mujeres con actividad sexual