Neuromyelitis Optica (NMO) is an autoimmune demyelinating disease of the central nervous system characterized by the presence of autoantibodies (called NMO-IgG) targeting aquaporin-4. Aquaporin-4 is expressed at the perivascular foot processes of astrocytes, in the glia limitans but also at the ependyma. Most studies have focus on studying the pathogenicity of NMO-IgG on astrocytes and NMO is now considered an astrocytopathy. However, periependymal lesions are observed in NMO suggesting that ependymal cells could also be targeted by NMO-IgG. Ependymal cells regulate CSF-parenchyma molecular exchanges, CSF flow and is a niche for subventricular neural stem cells. Our aim was to examine the effect of antibodies from NMO patients on ependymal cells. We exposed two models, i.e., primary culture of rat ependymal cells and explant cultures of rat lateral ventricular wall wholemounts, to purified IgG of NMO patients (NMO-IgG) for 24 hours. We then evaluated the treatment effect using immunolabeling, functional assays, ependymal flow analysis and bulk RNA sequencing. For each experiment, the effects were compared to purified IgG of healthy donor and to non-treated cells. We found that: i) NMO-IgG patients induced AQP4 agglomeration at the surface of ependymal cells, and induced cell enlargement in comparison to controls. In parallel, it induced an increase in gap junction connexin-43 plaque size; ii) NMO-IgG altered the orientation of ciliary basal bodies and functionally impaired cilia motility; iii) NMO-IgG activated the proliferation of subventricular neural stem cells; and iv) treatment with NMO-IgG upregulated the expression of pro-inflammatory cytokines and chemokines in the transcriptomic analysis. Our study showed that NMO-IgG can trigger an early and specific reactive phenotype in ependymal cells, with functional alterations of intercellular communication and cilia, activation of the subventricular stem cell proliferation and the secretion of pro-inflammatory cytokines. These findings suggest a key role for ependymal cells in the early phase of NMO lesion formation.
Freshwater fishes are widely stocked to enhance existing stocks and create new fishery opportunities, but quantification of ecological effects of stocking on recipient communities is still limited. Here, we quantified recent stocking practices in geographically close gravel pit lakes with contrasting history and management, and measured effects of stocking on fish community structure (taxonomic and functional diversity and body-size structure). Between 2011 and 2017, 50% of managers stocked fish into gravel pit lakes at least once. However, stocking density (1.6 kg.year −1 .ha −1 to 907 kg. year −1 .ha −1 ), stocking diversity, and species stocked (from rainbow trout-dominated to cyprinid-dominated) were highly variable. Stocking intensity and choice of stocked species were primarily driven by management objectives and lake size. Stocking intensity was associated with changes in the recipient fish community, with an increase in taxonomic and functional richness and nonlinear changes in community size spectrum. Our findings demonstrate that recent stocking practices can modulate ecological dynamics of fish communities in gravel pit lakes with important consequences on functional characteristics that should be incorporated into management practices.
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