In humans, pronounced age differences between parents have deleterious fitness consequences. In particular, the number of children is lower when mothers are much older than fathers. However, previous analyses failed to disentangle the influence of differential parental age from a direct age effect of each parent. In this study, we analyse the fitness consequences of both parental age and parental age differences on litter size and offspring survival in two closely related species of lemurs living in captivity. As captive lemurs do not choose their reproductive partner, we were able to measure litter size and offspring survival across breeding pairs showing a wide range of parental age differences. However, we demonstrated that the effect of the parental age difference on litter size was fully accounted for by female reproductive senescence because females mating with much younger males were old females. On the other hand, both parental age difference and female reproductive senescence influenced offspring survival. Our results emphasize the importance of teasing apart the effect of parental reproductive senescence when investigating the health and fitness consequences of parental age differences and also provide new insights for conservation programmes of endangered species.
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.
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