Exosomes secreted by cortical neurons upon glutamatergic synapse activation specifically interact with neurons

Exosomes are nano-sized vesicles of endocytic origin released into the extracellular space upon fusion of multivesicular bodies with the plasma membrane. Exosomes represent a novel mechanism of cell–cell communication allowing direct transfer of proteins, lipids and RNAs. In the nervous system, both glial and neuronal cells secrete exosomes in a way regulated by glutamate. It has been hypothesized that exosomes can be used for interneuronal communication implying that neuronal exosomes should bind to other neurons with some kind of specificity. Here, dissociated hippocampal cells were used to compare the specificity of binding of exosomes secreted by neuroblastoma cells to that of exosomes secreted by cortical neurons. We found that exosomes from neuroblastoma cells bind indiscriminately to neurons and glial cells and could be endocytosed preferentially by glial cells. In contrast, exosomes secreted from stimulated cortical neurons bound to and were endocytosed only by neurons. Thus, our results demonstrate for the first time that exosomes released upon synaptic activation do not bind to glial cells but selectively to other neurons suggesting that they can underlie a novel aspect of interneuronal communication

What is the 'problem' that outreach work seeks to address and how might it be tackled? Seeking theory in a primary health prevention programme

<b>Background</b> Preventive approaches to health are disproportionately accessed by the more affluent and recent health improvement policy advocates the use of targeted preventive primary care to reduce risk factors in poorer individuals and communities. Outreach has become part of the health service response. Outreach has a long history of engaging those who do not otherwise access services. It has, however, been described as eclectic in its purpose, clientele and mode of practice; its effectiveness is unproven. Using a primary prevention programme in the UK as a case, this paper addresses two research questions: what are the perceived problems of non-engagement that outreach aims to address; and, what specific mechanisms of outreach are hypothesised to tackle these.<p></p> <b>Methods</b> Drawing on a wider programme evaluation, the study undertook qualitative interviews with strategically selected health-care professionals. The analysis was thematically guided by the concept of 'candidacy' which theorises the dynamic process through which services and individuals negotiate appropriate service use.<p></p> <b>Results</b> The study identified seven types of engagement 'problem' and corresponding solutions. These 'problems' lie on a continuum of complexity in terms of the challenges they present to primary care. Reasons for non-engagement are congruent with the concept of 'candidacy' but point to ways in which it can be expanded.<p></p> <b>Conclusions</b> The paper draws conclusions about the role of outreach in contributing to the implementation of inequalities focused primary prevention and identifies further research needed in the theoretical development of both outreach as an approach and candidacy as a conceptual framework

Alix is required for activity-dependent bulk endocytosis at brain synapses

In chemical synapses undergoing high frequency stimulation, vesicle components can be retrieved from the plasma membrane via a clathrin-independent process called activitydependent bulk endocytosis (ADBE). Alix (ALG-2-interacting protein X/PDCD6IP) is an adaptor protein binding to ESCRT and endophilin-A proteins which is required for clathrinindependent endocytosis in fibroblasts. Alix is expressed in neurons and concentrates at synapses during epileptic seizures. Here, we used cultured neurons to show that Alix is recruited to presynapses where it interacts with and concentrates endophilin-A during conditions triggering ADBE. Using Alix knockout (ko) neurons, we showed that this recruitment, which requires interaction with the calcium-binding protein ALG-2, is necessary for ADBE. We also found that presynaptic compartments of Alix ko hippocampi display subtle morphological defects compatible with flawed synaptic activity and plasticity detected electrophysiologically. Furthermore, mice lacking Alix in the forebrain undergo less seizures during kainate-induced status epilepticus and reduced propagation of the epileptiform activity. These results thus show that impairment of ADBE due to the lack of neuronal Alix leads to abnormal synaptic recovery during physiological or pathological repeated stimulations

Intra-subject repeatability of in vivo intervertebral motion parameters using quantitative fluoroscopy.

Purpose: In vivo quantification of intervertebral motion through imaging has progressed to a point where biomarkers for low back pain are emerging. This makes possible deeper study of the condition’s biometrics. However, the measurement of change over time involves error. The purpose of this prospective investigation is to determine the intra-subject repeatability of six in vivo intervertebral motion parameters using quantitative fluoroscopy. Methods: Intra-subject reliability (ICC) and minimal detectable change (MDC) of baseline to 6-week follow-up measurements were calculated for 6 lumbar spine intervertebral motion parameters in 109 healthy volunteers. A standardised quantitative fluoroscopy (QF) protocol was used to provide measurements in the coronal and sagittal planes using both passive recumbent and active weight bearing motion. Parameters were: intervertebral range of motion (IV-RoM), laxity, motion sharing inequality (MSI), motion sharing variability (MSV), flexion translation, and anterior disc height change during flexion. Results: The best overall intra subject reliability (ICC) and agreement (MDT) were for disc height (ICC 0.89, MDC 43%) and IV-RoM (ICC 0.96, MDC 60%) and the worst for MSV (ICC 0.04, MCD 408%). Laxity, MSI and translation had acceptable reliability (most ICCs >0.60), but not agreement (MDC >85%). Conclusion: Disc height and IV-RoM measurement using QF could be considered for randomised trials while laxity, MSI and translation could be considered for moderators, correlates or mediators of patient reported outcomes. MSV had both poor reliability and agreement over 6 weeks

Ontogenèse des hormones de l'axe somatotrope

International audienc

Increased Alix (apoptosis-linked gene-2 interacting protein X) immunoreactivity in the degenerating striatum of rats chronically treated by 3-nitropropionic acid.

Chronic intoxication by 3-nitropropionic acid in the Lewis rat reproduces many features reminiscent of Huntington's disease including behavioural alterations and cortico-striatal degeneration. In particular, in this model, striatal degeneration is accompanied by calpain activation as found in the human disease. The present study was undertaken to determine whether the expression of Alix (apoptosis linked gene-2 interacting protein), a widespread protein involved in neuronal death, would be modified in the striatum and cortex of 3NP-treated rats. The results clearly show that Alix immunoreactivity is increased in the neuronal cell bodies of the lateral striatum, where degeneration is massive. The medial striatum and the cortex that lack neurodegeneration remain only weakly labelled. This is further evidence suggesting an involvement of Alix in the events driving neuronal death.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe

Alix is required for activity-dependent bulk endocytosis at brain synapses.

In chemical synapses undergoing high frequency stimulation, vesicle components can be retrieved from the plasma membrane via a clathrin-independent process called activity-dependent bulk endocytosis (ADBE). Alix (ALG-2-interacting protein X/PDCD6IP) is an adaptor protein binding to ESCRT and endophilin-A proteins which is required for clathrin-independent endocytosis in fibroblasts. Alix is expressed in neurons and concentrates at synapses during epileptic seizures. Here, we used cultured neurons to show that Alix is recruited to presynapses where it interacts with and concentrates endophilin-A during conditions triggering ADBE. Using Alix knockout (ko) neurons, we showed that this recruitment, which requires interaction with the calcium-binding protein ALG-2, is necessary for ADBE. We also found that presynaptic compartments of Alix ko hippocampi display subtle morphological defects compatible with flawed synaptic activity and plasticity detected electrophysiologically. Furthermore, mice lacking Alix in the forebrain undergo less seizures during kainate-induced status epilepticus and reduced propagation of the epileptiform activity. These results thus show that impairment of ADBE due to the lack of neuronal Alix leads to abnormal synaptic recovery during physiological or pathological repeated stimulations

Utz Wachil: Findings from an International Study of Indigenous Perspectives on Health and Environment

This article reports previously unpublished results of a collaborative study undertaken in 2003 by health workers of the UK-based organisation Health Unlimited, and by researchers of the London School of Hygiene and Tropical Medicine. This study marked the first of a series of collaborative activities aimed at highlighting the situation of Indigenous peoples, some in the most isolated ecosystems of the planet. While many researchers focus on quantitative analysis of the health and environmental conditions of Indigenous peoples, our 2003 study aimed at exploring the views of Indigenous peoples in isolated communities in five countries on their environment and their health. In this article we look closely at the web of knowledge and belief that underpins Indigenous peoples' concepts of health and well-being, and their relationship to land and the environment. Although many Indigenous people have been forced off their traditional lands and live in rural settlements, towns, and cities, there are still a large number of people living in very small Indigenous communities in remote areas. This article focuses on 20 such communities in six countries. We explore traditional knowledge and practice and its relationship to Western medicine and services. The research findings highlight the importance of Indigenous knowledge systems for the emerging ecohealth community and suggest that we have much to learn from Indigenous peoples in our pursuit of a more holistic science