Microglia Responses in Acute and Chronic Neurological Diseases: What Microglia-Specific Transcriptomic Studies Taught (and did Not Teach) Us

Over the last decade, microglia have been acknowledged to be key players in central nervous system (CNS) under both physiological and pathological conditions. They constantly survey the CNS environment and as immune cells, in pathological contexts, they provide the first host defense and orchestrate the immune response. It is well recognized that under pathological conditions microglia have both sequential and simultaneous, beneficial and detrimental effects. Cell-specific transcriptomics recently became popular in Neuroscience field allowing concurrent monitoring of the expression of numerous genes in a given cell population. Moreover, by comparing two or more conditions, these approaches permit to unbiasedly identify deregulated genes and pathways. A growing number of studies have thus investigated microglial transcriptome remodeling over the course of neuropathological conditions and highlighted the molecular diversity of microglial response to different diseases. In the present work, we restrict our review to microglia obtained directly from in vivo samples and not cell culture, and to studies using whole-genome strategies. We first critically review the different methods developed to decipher microglia transcriptome. In particular, we compare advantages and drawbacks of flow cytometry and laser microdissection to isolate pure microglia population as well as identification of deregulated microglial genes obtained via RNA sequencing (RNA-Seq) vs. microarrays approaches. Second, we summarize insights obtained from microglia transcriptomes in traumatic brain and spinal cord injuries, pain and more chronic neurological conditions including Amyotrophic lateral sclerosis (ALS), Alzheimer disease (AD) and Multiple sclerosis (MS). Transcriptomic responses of microglia in other non-neurodegenerative CNS disorders such as gliomas and sepsis are also addressed. Third, we present a comparison of the most activated pathways in each neuropathological condition using Gene ontology (GO) classification and highlight the diversity of microglia response to insults focusing on their pro- and anti-inflammatory signatures. Finally, we discuss the potential of the latest technological advances, in particular, single cell RNA-Seq to unravel the individual microglial response diversity in neuropathological contexts

Rapid and Differential Regulation of AMPA and Kainate Receptors at Hippocampal Mossy Fibre Synapses by PICK1 and GRIP

AbstractWe identified four PDZ domain-containing proteins, syntenin, PICK1, GRIP, and PSD95, as interactors with the kainate receptor (KAR) subunits GluR52b, GluR52c, and GluR6. Of these, we show that both GRIP and PICK1 interactions are required to maintain KAR-mediated synaptic function at mossy fiber-CA3 synapses. In addition, PKCα can phosphorylate ct-GluR52b at residues S880 and S886, and PKC activity is required to maintain KAR-mediated synaptic responses. We propose that PICK1 targets PKCα to phosphorylate KARs, causing their stabilization at the synapse by an interaction with GRIP. Importantly, this mechanism is not involved in the constitutive recycling of AMPA receptors since blockade of PDZ interactions can simultaneously increase AMPAR- and decrease KAR-mediated synaptic transmission at the same population of synapses

What place do social medias take in the online marketing and advertising space? An exploratory case study of Facebook's marketing solutions

This research is aiming to help marketers that require a deep understanding of social media. In a more complex, fast paced and changing digital environment, marketers need to quickly adapt their marketing strategy aligned with their business goals and use the right channels of communication on the Internet to reach their target audience. Today the digital environment offer various tools to advertise and promote products or services. New technologies have accelerated and influenced the digital landscape. New companies have recently emerged and have changed the way consumers communicate on the Internet. For instance, using social media networks today is a normal part of life for millions of people worldwide and this gives huge opportunities for marketers to reach precisely their audience and create a true connection between their organization and consumers. As social media is a new area for marketers, this research is focusing on all the aspects and the challenges that excite the marketing community. As Facebook is by far the most used social media platform, with more than 955 million monthly active users worldwide, a case study will be used to help marketers to understand how they can utilise Facebook marketing solutions in the most efficient way aligned with their marketing objectives. Some companies in different varied industries will also benefit from understanding their potential marketing success on the Facebook social media platform. This will help marketers to use social media in the most efficient way and give them the ability to respond to their marketing objectives while creating real online connection with their clients

Le complexe basique de Belle-Isle-en-terre (Côtes-du-Nord)

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La place de la concertation dans la mise en oeuvre de projets urbains durables à travers l'exemple de l'agglomération parisienne : territoires, acteurs, représentations

Since Rio 1992, consultation has become an essential political and social practice. It responds to a request from citizens to participate in public debate, decision-making, local management and the city's factory. Consultation, which has become regulatory and brings together a plurality of actors, is the place and time when issues of governance, territorial management and urban sustainability are at stake. The thesis seeks to answer the following questions: to what extent are governance processes, put into practice through consultation and resulting from environmental public policies, effective in territorial planning strategies ? How to measure the effects of these processes? What roles do these processes play in the development of land-use patterns? The scientific approach used was based on observation of consultation meetings. The surveys were carried out in the territories of the Greater Paris Metropolis, which is changing as a result of the metropolization of the territory and the application of the principles of urban sustainability.The survey made it possible to compare the representations of the in habitants and those of the project leaders with regard to the evaluation of participation, the objects that make up the territory and the spatial representations. This confrontation of representations highlights the dissonances and meeting points between these categories of actors. Another part of the thesis attempted to understand the inhabitants' motivation for participation, their expectations and spatial practices. As a result of these surveys, it appears that the "city factory" can no longer be built without the inhabitants - users who want to be informed about urban projects and heard by project leaders. However, when consultation is taken seriously by all stakeholders, it tends to best meet the principles of urban sustainability.Depuis Rio 1992, la concertation est devenue une pratique politique et sociale incontournable. Elle répond à une demande des citoyens de participer au débat public, à la prise de décision, à la gestion locale et à la fabrique de la ville. La concertation, devenue réglementaire et réunissant une pluralité d'acteurs, est le lieu et le moment où se posent des enjeux de gouvernance, de gestion territoriale et de durabilité urbaine. La thèse cherche à répondre aux questions suivantes : dans quelles mesures les processus de gouvernance, mis en pratique par la concertation et issus des politiques publiques environnementales, sont-ils efficaces dans les stratégies d'aménagement territorial ? Comment mesurer les effets de ces processus ? Quels rôles ces processus jouent-ils dans l'élaboration des modes d'habiter des territoires? La méthodologie mise en œuvre s'est appuyée l'observation de réunions de concertation. Les enquêtes ont été menées dans des territoires de la Métropole du Grand Paris qui se transforme sous l'effet de la métropolisation du territoire et de l'application des principes de durabilité urbaine. L'enquête a permis de mettre en regard les représentations des habitants et celles des porteurs de projet quant à l'évaluation de la participation, aux objets qui font territoire et aux représentations spatiales. Cette confrontation des représentations souligne les dissonances et les points de rencontre entre ces catégories d'acteurs. Un autre volet de la thèse a tenté d'appréhender la motivation des habitants à la participation, leurs attentes et leurs pratiques spatiales. À l'issue de ces enquêtes, il apparaît que la «fabrique de la ville» ne peut désormais se faire sans les habitants - usagers qui veulent être informés des projets urbains et entendus par les porteurs de projet. Cependant, quand la concertation est prise au sérieux par tous les acteurs, elle tend à répondre au mieux aux principes de la durabilité urbaine

Gacyclidine: A New Neuroprotective Agent Acting at the N-Methyl-D-Aspartate Receptor

International audienc

La zone broyée Nord-armoricaine au niveau de Belle-Isle-en-Terre (C.d. N.)

National audienc

P2X4 receptors mediate PGE2 release by tissue-resident macrophages and initiate inflammatory pain

International audienc