SUMMARY Adult hippocampal neurogenesis is believed to maintain a range of cognitive functions, many of which decline with age. We recently reported that radial neural stem cells (rNSCs) in the hippocampus undergo activation-dependent conversion into astrocytes, a mechanism that over time contributes to a reduction in the rNSC population. Here, we injected low and high levels of kainic acid (KA) in the dentate gyrus to assess whether neuronal hyperexcitation, a hallmark of epileptic disorders, could accelerate this conversion. At low levels of KA, generating epileptiform activity without seizures, we indeed found increased rNSC activation and conversion into astrocytes. At high levels, generating sustained epileptic seizures, however, we find that rNSCs divide symmetrically and that both mother and daughter cells convert into reactive astrocytes. Our results demonstrate that a threshold response for neuronal hyperexcitation provokes a dramatic shift in rNSCs function, which impairs adult hippocampal neurogenesis in the long term.

During adult hippocampal neurogenesis, most newborn cells undergo apoptosis and are rapidly phagocytosed by resident microglia to prevent the spillover of intracellular contents. Here, we propose that phagocytosis is not merely passive corpse removal but has an active role in maintaining neurogenesis. First, we found that neurogenesis was disrupted in male and female mice chronically deficient for two phagocytosis pathways: the purinergic receptor P2Y12, and the tyrosine kinases of the TAM family Mer tyrosine kinase (MerTK)/Axl. In contrast, neurogenesis was transiently increased in mice in which MerTK expression was conditionally downregulated. Next, we performed a transcriptomic analysis of the changes induced by phagocytosis in microglia in vitro and identified genes involved in metabolism, chromatin remodeling, and neurogenesis-related functions. Finally, we discovered that the secretome of phagocytic microglia limits the production of new neurons both in vivo and in vitro. Our data suggest that microglia act as a sensor of local cell death, modulating the balance between proliferation and survival in the neurogenic niche through the phagocytosis secretome, thereby supporting the longterm maintenance of adult hippocampal neurogenesis.

Insertion sequence 91 (IS91) inserts specifically at GTTC or CTTG target sequences without dupliation ofthe target. After insertion, the right inverted repeat (IRt) lies adjacent to the 3' end of the target sequences (or 5' to the complementary sequence CAAG or GAAC). We have analyzed the effects of alteration of each terminus of IS91 on transposition activity in Escherichia coil. IRR is absolutely required for transposition. Deletion analys iicates that a 14-bp segent is not sufficient, but an 81-bp sequence within the IRR region is sufficient. Furthermore, the GTTC/CTTG target site is also required. The left inverted repeat (IRL) of IS91 is dispensable. Plasmid fusions originated by one-ended transposition of IS91 derivatives lacking IRL occur at about the same frequency as cointegrate formation observed for the wild-type element. In the one-ended-type fusions, the inserted fra et of donor DNA is flanked at one end (constant end) by IRR and at the other end by a GTTC or CTTG sequence present in the donor (variable end) in a way that usually results in multiple tandem insertions of the donor plasmid in the target site. These results are easily accommodated by a rolling-circle replicative transposition mechanism. This model also draws support from the finding that the IS91 ta is related in sequence to the superfamily of rdling-circle replication proteins and the observation that IRR shows some conservation in sequence and secondary structure with the origins of replication of some rolling-circle replication plids.Transposons are genetic elements able to move to many different genome loci in their hosts, therefore contributing significantly to genome diversity. They have been classified into subgroups based on their transposition mechanism or the sequence similarities between their transposition proteins (1). The mechanisms of the early steps in transposition of a few diverse well-studied transposons display a remarkable similarity in their basic three-step mechanism: nuclease cut, strand transfer, and replication or repair, depending on whether the transposition is replicative (Tn3, replicative Mu) or conservative (Tn7, TnlO, lysogenic Mu) (2).Insertion sequence 91 (IS91) displays a number of characteristics that are unique among IS elements, suggesting an unusual transposition mechanism. First, it shows an absolute insertion specificity for the target sequence GAAC or CAAG; it inserts at the 5' end of these sequences so that its right inverted repeat (IRR) lies adjacent to the specific target site. Furthermore, the target DNA is not duplicated (3). Analysis of the IS91 DNA sequence (4, 5) indicates that (i) its transposase is related to a family of replication proteins of plasmids that replicate by rolling-circle (RCR plasmids) (4), and (ii) the termini of IS91 form a very short IR (7 bp with one mismatch). The latter finding suggests that a protein operating at the IRs will also recognize unique sequences at each end, raising the possibility that each terminus plays a different role in IS91 transpositi...

BackgroundThe impact of nano-scaled materials on photosynthetic organisms needs to be evaluated. Plants represent the largest interface between the environment and biosphere, so understanding how nanoparticles affect them is especially relevant for environmental assessments. Nanotoxicology studies in plants allude to quantum size effects and other properties specific of the nano-stage to explain increased toxicity respect to bulk compounds. However, gene expression profiles after exposure to nanoparticles and other sources of environmental stress have not been compared and the impact on plant defence has not been analysed.ResultsArabidopsis plants were exposed to TiO2-nanoparticles, Ag-nanoparticles, and multi-walled carbon nanotubes as well as different sources of biotic (microbial pathogens) or abiotic (saline, drought, or wounding) stresses. Changes in gene expression profiles and plant phenotypic responses were evaluated. Transcriptome analysis shows similarity of expression patterns for all plants exposed to nanoparticles and a low impact on gene expression compared to other stress inducers. Nanoparticle exposure repressed transcriptional responses to microbial pathogens, resulting in increased bacterial colonization during an experimental infection. Inhibition of root hair development and transcriptional patterns characteristic of phosphate starvation response were also observed. The exogenous addition of salicylic acid prevented some nano-specific transcriptional and phenotypic effects, including the reduction in root hair formation and the colonization of distal leaves by bacteria.ConclusionsThis study integrates the effect of nanoparticles on gene expression with plant responses to major sources of environmental stress and paves the way to remediate the impact of these potentially damaging compounds through hormonal priming.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-015-1530-4) contains supplementary material, which is available to authorized users.

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