Reconsolidation‐induced rescue of a remote fear memory blocked by an early cortical inhibition: Involvement of the anterior cingulate cortex and the mediation by the thalamic nucleus reuniens

Systems consolidation is a time‐dependent reorganization process involving neocortical and hippocampal networks underlying memory storage and retrieval. The involvement of the hippocampus during acquisition is well described; however we know much less about the concomitant contribution of cortical activity levels to the formation of stable remote memories. Here, after a reversible pharmacological inhibition of the anterior cingulate cortex (ACC) during the acquisition of a contextual fear conditioning, retrieval of both recent and remote memories were impaired, an effect that was reverted by a single memory reactivation session 48 h after training, through a destabilization‐dependent mechanism interpreted as reconsolidation, that restored the normal course of systems consolidation in order to rescue a remote memory. Next we have shown that the integrity of both the anterior cingulate cortex and the thalamic nucleus reuniens (RE) were required for this reactivation‐induced memory rescue. Because lidocaine infused into the RE inhibited LTP induction in the CA1‐anterior cingulate cortex pathways, it seems that RE is a necessary component of the circuit underlying systems consolidation, mediating communication between dorsal hippocampus and cortical areas. To our notice, this is the first demonstration of the rescue of remote memories disrupted by ACC inhibition during acquisition, via a reconsolidation‐driven mechanism. We have also shown the importance of RE to ensure the interconnection among brain areas that collectively seem to control the natural course of systems consolidation and allow the persistence of relevant emotional engrams. © 2017 Wiley Periodicals, Inc.     

Clinical features and myofascial pain syndrome in older adults with knee osteoarthritis by sex and age distribution: A cross-sectional study

Background

A source of myofascial pain and myofascial trigger points (MTrPs) in muscles of the knee area could play a crucial role in the management of pain in osteoarthritis patients. The aim of this study was to describe and compare demographic, clinical and myofascial pain syndrome characteristics in older adults with knee osteoarthritis by sex and age distribution.

Restitution of gut microbiota in Ugandan children administered with probiotics (Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12) during treatment for severe acute malnutrition

ABSTRACT

Severe acute malnutrition (SAM) is a major challenge in low-income countries and gut microbiota (GM) dysbiosis may play a role in its etiology. Here, we determined the GM evolution during rehabilitation from SAM and the impact of probiotics (Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12) supplementation. The GM (16S rRNA gene amplicon sequencing) of children admitted to hospital with SAM showed distinct composition over admission (e.g. Klebsiella spp., and Enterobacteriaceae spp.), discharge (e.g. Clostridiaceae spp., Veilonella dispar) and follow-up (e.g. Lactobacillus ruminis, Blautia spp., Faecalibacterium prausnitzii), reaching similar β- and α-diversity as healthy individuals. Children with diarrhea had reduced distribution of Bacteroidaceae, Lachnospiraceae, increased Enterobacteriaceae and Moraxellaceae, and lower α-diversity. Children suffering from edematous SAM had diminished proportion of Prevotellaceae, Lachnospiraceae, Ruminoccaceae and a higher α-diversity when compared to non-edematous SAM. Supplementation of probiotics did not influence β-diversity upon discharge or follow-up, but it increased (p < .05) the number of observed species [SE: > 4.5]. Children where the probiotic species were detected had lower cumulative incidence (p < .001) of diarrhea during the follow-up period compared to children receiving placebo and children receiving probiotics, but where the probiotics were not detected. The GM of children with non-edematous and edematous SAM differ in composition, which might have implications for future GM targeted treatments. Probiotics treatment reduced the cumulative incidence of diarrhea during the outpatient phase, with the strongest effect in children where the administered probiotics could be detected in the GM.     

Stimulation of invariant natural killer T cells by α‐Galactosylceramide activates the JAK‐STAT pathway in endothelial cells and reduces angiogenesis in the 5T33 multiple myeloma model

Tumour pathogenesis in multiple myeloma (MM) correlates with a high vascular index. Therefore, targeting angiogenesis is an important therapeutic tool to reduce MM progression. This study aimed to investigate the role of invariant natural killer T (iNKT) cells in angiogenesis and the mechanisms behind the stimulation by α‐Galactosylceramide (α‐GalCer). We have previously found that α‐GalCer could increase the survival of 5T33MM mice and here we demonstrate that α‐GalCer reduces the microvessel density. We performed both in vivo and in vitro angiogenic assays to confirm this observation. We found that conditioned medium of α‐GalCer stimulated iNKT cells reduced neovascularization in the chick chorioallantoic membrane and in matrigel plug assays. Moreover, we observed a reduction in proliferation, migration and network formation and an induction of apoptosis upon exposure of murine endothelial cell lines to this conditioned medium. We furthermore observed that the JAK‐STAT signaling pathway was highly activated in endothelial cells in response to stimulated iNKT cells, indicating the possible role of IFN‐γ in the anti‐angiogenic process. In conclusion, these results highlight the possibility of recruiting iNKT cells to target MM and angiogenesis. This gives a rationale for combining immunotherapy with conventional anti‐tumour treatments in view of increasing their therapeutic potential.