13 research outputs found
Le rÎle des microglies et de l'inflammation dans l'ischémie cérébrale
L'ischĂ©mie cĂ©rĂ©brale induit une rĂ©ponse inflammatoire aiguĂ« et prolongĂ©e caractĂ©risĂ©e par la production de cytokines, l'infiltration de leukocytes dans le cerveau, ainsi que l'activation des cellules gliales rĂ©sidentes dont les microglies. Les microglies sont impliquĂ©es dans l'Ă©limination des dĂ©bris cellulaires, la production de cytokines proinflammatoires et de facteurs trophiques. Un rĂŽle neuroprotecteur des microglies suite Ă une dĂ©gĂ©nĂ©rescence du SNC est proposĂ© dans la littĂ©rature. Cependant, l'activation des cellules microgliales est aussi associĂ©e avec la sĂ©crĂ©tion de molĂ©cules toxiques et l'attĂ©nuation de l'activation microgliale est bĂ©nĂ©fique dans certaines maladies neurodegeneratives. Dans l'ischĂ©mie cĂ©rĂ©brale, le rĂŽle de la prolifĂ©ration microgliale et de la dynamique de la rĂ©ponse inflammatoire reste mĂ©connu. L'analyse de la souris CDllb-TKmutÂłâ° aprĂšs l'ischĂ©mie cĂ©rĂ©brale, a permis de montrer que l'Ă©limination sĂ©lective des microglies en prolifĂ©ration amplifie la rĂ©ponse inflammatoire aprĂšs l'ischĂ©mie cĂ©rĂ©brale et augmente la taille de la lĂ©sion ischĂ©mique. La caractĂ©risation de cette population a permis de dĂ©terminer que les premiĂšres cellules microgliales Ă prolifĂ©rer sont les cellules rĂ©sidentes exprimant le marqueur d'activation galectine-3. De plus, aprĂšs l'ischĂ©mie cĂ©rĂ©brale, cette population sert de source endogĂšne d'IGF-1, une molĂ©cule neurotrophique. L'inactivation gĂ©nĂ©tique de la galectine 3 chez la souris a permis de confirmer le rĂŽle bĂ©nĂ©fique de cette population microgliale ainsi que de lien potentiel entre la galectine 3 et l'induction de la rĂ©ponse mitogĂ©nique d'IGF-1. De plus, l'Ă©tude longitudinale de l'activation des microglies Ă l'aide la souris transgĂ©nique TLR2-Fluc-GFP a permis de montrer que l'activation microgliale aprĂšs l'ischĂ©mie cĂ©rĂ©brale est biphasique et perdure plusieurs mois aprĂšs l'attaque initiale. Deux sites majeurs d'activation ont pu aussi ĂȘtre dĂ©tectĂ©s : la rĂ©gion ischĂ©mique et le bulbe olfactif. D'ailleurs, l'augmentation de signal au site de la lĂ©sion ischĂ©mique est toujours prĂ©cĂ©dĂ©e par une augmentation significative du signal TLR2 dans le bulbe olfactif. Par leur position anatomique particuliĂšre, les cellules microgliales du bulbe olfactif sont plus sensibles aux signaux provenant autant de l'environnement que de l'intĂ©rieur du cerveau et pourraient servir de senseurs et/ou modulateurs de l'inflammation cĂ©rĂ©brale. Les rĂ©sultats obtenus par l'Ă©tude de diffĂ©rents modĂšles de souris transgĂ©niques ont permis de montrer la dynamique de la rĂ©ponse inflammatoire, le rĂŽle neuroprotecteur des microglies en prolifĂ©ration et le lien potentiel entre la galectine 3 et le facteur neuroprotecteur IGF-
Gender-specific associations between functional autonomy and physical capacities in independent older adults: Results from the NuAge study
Abstract : Background: Even with healthy and active aging, many older adults will experience a decrease in physical capacities. This decrease might be associated with diminished functional autonomy. However, little is known about the physical capacities associated with functional autonomy in older women and men. Objective: This study aimed to examine gender-specific associations between functional autonomy and physical capacities in independent older women and men. Methods: Secondary analyses were carried out using cross-sectional data from 652 women and 613 men who participated in the NuAge longitudinal study. The "functional autonomy measurement system" (SMAF) was used to evaluate functional autonomy. The physical capacities measured (tests used) were: biceps and quadriceps strength (Microfet dynamometer), grip strength (Martin vigorimeter), unipodal balance, changing position & walking (timed up and go), normal & fast walking (four-meter walking speed) and changing position (chair stand). Correlation and multiple linear regression analyses adjusted for age, depressive symptoms and body composition were performed. Results: On average, participants were aged 73 years and had mild to moderate functional autonomy loss. In women, after controlling for age, depressive symptoms and body composition, greater functional autonomy was best explained by faster changing position & walking skills and superior biceps strength (R2 = 0.46; p < 0.001). After controlling for depressive symptoms, faster changing position & walking skills and better unipodal balance best explained greater functional autonomy in men (R2 = 0.21; p < 0.001). Conclusion: According to these results, physical capacities are moderately associated with functional
autonomy among independent older adults, especially women
Lipopolysaccharide-QD micelles induce marked induction of TLR2 and lipid droplet accumulation in olfactory bulb microglia
The intranasal entry of biological and artificial nanoparticles can induce inflammatory responses both locally and more widely in surrounding tissues. The aim of this study was to assess the microglia activation induced by nanoparticles with different surfaces in (i) a transgenic mouse (Toll-like receptor (TLR)-2-luciferase (Luc) reporter) which allowed the biophotonic imaging of microglial activation/innate immune response after intranasal delivery of nanoparticles and (ii) in microglial dispersed cells in vitro. Cadmium selenide nanoparticles (quantum dots, QD), surface-exchanged with lipopolysaccharide (LPS) to form micelles, were tested to assess microglia activation and lipid droplet formation in both model systems. In vivo imaging revealed a robust increase in the extent of microglial activation/TLR2 response, initially in the olfactory bulb, but also in other more caudal brain regions. The increased TLR2 expression was complemented with enhanced CD68 expression in activated microglia in the same regions. [...
Diverging mRNA and Protein Networks in Activated Microglia Reveal SRSF3 Suppresses Translation of Highly Upregulated Innate Immune Transcripts
Uncontrolled microglial activation may lead to the development of inflammation-induced brain damage. Here, we uncover a ribosome-based mechanism/checkpoint involved in control of the innate immune response and microglial activation. Using an in vivo model system for analysis of the dynamic translational state of microglial ribosomes, with mRNAs as input and newly synthesized peptides as an output, we find a marked dissociation of microglia mRNA and protein networks following innate immune challenge. Highly upregulated and ribosome-associated mRNAs were not translated, resulting in two distinct microglial molecular signatures, a highly specialized pro-inflammatory mRNA signature and an immunomodulatory/homeostatic protein signature. We find that this is due to specific translational suppression of highly expressed mRNAs through a 3âČ UTR-mediated mechanism involving the RNA-binding protein SRSF3. This discovery suggests avenues for therapeutic modulation of innate immune response in resident microglia