The Antidepressant Fluoxetine Mobilizes Vesicles to the Recycling Pool of Rat Hippocampal Synapses During High Activity

Effects of the antidepressant fluoxetine in therapeutic concentration on stimulation-dependent synaptic vesicle recycling were examined in cultured rat hippocampal neurons using fluorescence microscopy. Short-term administration of fluoxetine neither inhibited exocytosis nor endocytosis of RRP vesicular membranes. On the contrary, acute application of the drug markedly increased the size of the recycling pool of hippocampal synapses. This increase in recycling pool size was corroborated using the styryl dye FM 1-43, antibody staining with αSyt1-CypHer?5E and overexpression of synapto-pHluorin, and was accompanied by an increase in the frequency of miniature postsynaptic currents. Analysis of axonal transport and fluorescence recovery after photobleaching excluded vesicles originating from the synapse-spanning superpool as a source, indicating that these new release-competent vesicles derived from the resting pool. Super resolution microscopy and ultrastructural analysis by electron microscopy revealed that short-term incubation with fluoxetine had no influence on the number of active synapses and synaptic morphology compared to controls. These observations support the idea that therapeutic concentrations of fluoxetine enhance the recycling vesicle pool size and thus the recovery of neurotransmission from exhausting stimuli. The change in the recycling pool size is consistent with the plasticity hypothesis of the pathogenesis of major depressive disorder as stabilization of the vesicle recycling might be responsible for neural outgrowth and plasticity.     

Appetitive Aggression as a Resilience Factor against Trauma Disorders: Appetitive Aggression and PTSD in German World War II Veterans

Background

Repeated exposure to traumatic stressors such as combat results in chronic symptoms of PTSD. However, previous findings suggest that former soldiers who report combat-related aggression to be appetitive are more resilient to develop PTSD. Appetitive Aggression should therefore prevent widespread mental suffering in perpetrators of severe atrocities even after decades.

Methods and Findings

To test the long-term relationship between trauma-related illness and attraction to aggression, we surveyed a sample of 51 German male World-War II veterans (age: M = 86.7, SD = 2.8). War-related appetitive aggression was assessed with the Appetitive Aggression Scale (AAS). Current- and lifetime PTSD symptoms were assessed with the PSS-I. In a linear regression analysis accounting for 31% of the variance we found that veterans that score higher on the AAS show lower PSS-I symptom severity scores across their whole post-war lifetime (β = − .31, p = .014). The effect size and power were sufficient (f ² = 0.51, (1-β) = .99). The same was true for current PTSD (β = − .27, p = .030).

Conclusions

Appetitive Aggression appears to be a resilience factor for negative long-term effects of combat experiences in perpetrators of violence. This result has practical relevance for preventing trauma-related mental suffering in Peace Corps and for designing adequate homecoming reception for veterans.     

Knock-down of Pdcd4 stimulates angiogenesis via up-regulation of angiopoietin-2

The tumor suppressor Pdcd4 is involved in multiple pathways. Considering its biological action conflicting data in the literature exist and, consequently, our own studies point to a cell type specific action of Pdcd4. In the present study, using several Pdcd4 knock down cell lines we succeeded to identify angiopoietin-2 (Ang-2) as a gene up-regulated on the mRNA and protein level. The subsequent enhanced peptide secretion forced wild type Bon-1 cells in a neoplastic direction demonstrated by increased proliferation and colony formation while cell adhesion was decreased. Most likely, the stimulation of Ang-2 is in part mediated by increased activation of AP-1 but different signal transduction pathways may also be involved since we found opposite activation of PI3K/Akt/mTOR and MAPK7ERK pathways (both known to regulate in Ang-2 expression). Ang-2 is a modulator of vascular remodeling. Therefore, we analyzed the effect of supernatants from Pdcd4 knock-down cell lines on endothelial cells. Again, we detected reduced cell adhesion and increased colony formation. Probably, the most impressive effect was described on tube formation in a model for angiogenesis. Tube length and junctions of endothelial cells treated with conditioned medium from Pdcd4 knock-down cells were considerably increased. Both, up-regulation of Ang-2 and down-regulation of Pdcd4 are described for many tumors. However, this is the first study showing a direct impact of Pdcd4 on Ang-2 levels and, thereby, angiogenesis. Our data suggest a completely new mechanism for Pdcd4 to act as a tumor suppressor rendering Pdcd4 an attractive target for new therapeutic strategies in cancer treatment.     

Sea-anemone toxin ATX-II elicits A-fiber-dependent pain and enhances resurgent and persistent sodium currents in large sensory neurons

Background

Despite decades of intense research efforts, actions of acute opioids are not fully understood. Increasing evidence suggests that in addition to well-documented antinociceptive effects opioids also produce paradoxical hyperalgesic and excitatory effects on neurons. However, most studies focus on the pronociceptive actions of chronic opioid exposure. Matrix metalloproteinase 9 (MMP-9) plays an important role in neuroinflammation and neuropathic pain development. We examined MMP-9 expression and localization in dorsal root ganglia (DRGs) after acute morphine treatment and, furthermore, the role of MMP-9 in modulating acute morphine-induced analgesia and hyperalgesia in mice.

Results

Subcutaneous morphine induced a marked up-regulation of MMP-9 protein in DRGs but not spinal cords. Morphine also increased MMP-9 activity and mRNA expression in DRGs. MMP-9 up-regulation peaked at 2 h but returned to the baseline after 24 h. In DRG tissue sections, MMP-9 is expressed in small and medium-sized neurons that co-express mu opioid receptors (MOR). In DRG cultures, MOR agonists morphine, DAMGO, and remifentanil each increased MMP-9 expression in neurons, whereas the opioid receptor antagonist naloxone and the MOR-selective antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH₂ (CTAP) suppressed morphine-induced MMP-9 expression. Notably, subcutaneous morphine-induced analgesia was enhanced and prolonged in Mmp9 knockout mice and also potentiated in wild-type mice receiving intrathecal injection of MMP-9 inhibitors. Consistently, intrathecal injection of specific siRNA targeting MMP-9 reduced MMP-9 expression in DRGs and enhanced and prolonged morphine analgesia. Subcutaneous morphine also produced heat hyperalgesia at 24 h, but this opioid-induced hyperalgesia was not enhanced after MMP-9 deletion or inhibition.

Conclusions

Transient MMP-9 up-regulation in DRG neurons can mask opioid analgesia, without modulating opioid-induced hyperalgesia. Distinct molecular mechanisms (MMP-9 dependent and independent) control acute opioid-induced pronociceptive actions (anti-analgesia in the first several hours and hyperalgesia after 24 h). Targeting MMP-9 may improve acute opioid analgesia.     

Functional groups' performances as influenced by nitrogen,phosphorus and nodule inhibition of legumes

Aims Nitrogen (N) and phosphorus (P) constitute essential elements for plant growth and their availability influence species diversity in herbaceous plant communities. Legumes exhibit relatively high abundance in N-limited soils. Moreover, the legumes' N:P ratios are much higher than those of the other plant species grown in the same site, probably because they are able to fix atmospheric N 2. The objective of this study was to determine how the relative proportion in N and P availability and the restriction of legumes to fix atmospheric N 2 affect: (i) the primary productivity of plant species, (ii) species composition and (iii) N and P concentrations of species.Methods In an outdoor experiment, mixtures containing grasses, legumes and non-legume forbs were established in 32 containers under four soil treatments (control, N addition, P addition and disinfected soil), in a completely randomized design with eight replicates. Plant growth was examined when N and P were limited in the control soil:sand mixture, in a pot experiment sown with Plantago lanceolata .Important findings The pot experiment indicated that both N and P were limiting for the growth of P. lanceolata. Soil treatments affected primary productivity and species composition. Legumes had a relatively high abundance in the control and their growth was favoured, especially that of Medicago sativa, by P addition. Grasses' growth was increased by the addition of N. Inhibition of rhizobia resulted in poor growth of legumes and concomitant higher growth of grasses, in comparison to the control. The N:P ratios of non-legume species differed between treatments and were always higher in the legume species, even in the disinfected soil. The latter provides evidence that the high N concentrations found in legumes are a physiological characteristic of this specific group of plants.     

Landscape perspectives on agricultural intensification and biodiversity – ecosystem service management

Understanding the negative and positive effects of agricultural land use for the conservation of biodiversity, and its relation to ecosystem services, needs a landscape perspective. Agriculture can contribute to the conservation of high‐diversity systems, which may provide important ecosystem services such as pollination and biological control via complementarity and sampling effects. Land‐use management is often focused on few species and local processes, but in dynamic, agricultural landscapes, only a diversity of insurance species may guarantee resilience (the capacity to reorganize after disturbance). Interacting species experience their surrounding landscape at different spatial scales, which influences trophic interactions. Structurally complex landscapes enhance local diversity in agroecosystems, which may compensate for local high‐intensity management. Organisms with high‐dispersal abilities appear to drive these biodiversity patterns and ecosystem services, because of their recolonization ability and larger resources experienced. Agri‐environment schemes (incentives for farmers to benefit the environment) need to broaden their perspective and to take the different responses to schemes in simple (high impact) and complex (low impact) agricultural landscapes into account. In simple landscapes, local allocation of habitat is more important than in complex landscapes, which are in total at risk. However, little knowledge of the relative importance of local and landscape management for biodiversity and its relation to ecosystem services make reliable recommendations difficult.     

Local vs. landscape controls on diversity: a test using surface-dwelling soil macroinvertebrates of differing mobility

Aim A better understanding of the processes driving local species richness and of the scales at which they operate is crucial for conserving biodiversity in cultivated landscapes. Local species richness may be controlled by ecological processes acting at larger spatial scales. Very little is known about the effect of landscape variables on soil biota. The aim of our study was to partly fill this gap by relating the local variation of surface‐dwelling macroarthropod species richness to factors operating at the habitat scale (i.e. land use and habitat characteristics) and the landscape scale (i.e. composition of the surrounding matrix). Location An agricultural landscape with a low‐input farming system in Central Hesse, Germany. Methods We focused on five taxa significantly differing in mobility and ecological requirements: ants, ground beetles, rove beetles, woodlice, and millipedes. Animals were caught with pitfall traps in fields of different land use (arable land, grassland, fallow land) and different habitat conditions (insolation, soil humidity). Composition of the surrounding landscape was analysed within a radius of 250 m around the fields. Results Factors from both scales together explained a large amount of the local variation in species richness, but the explanatory strength of the factors differed significantly among taxa. Land use particularly affected ground beetles and woodlice, whereas ants and rove beetles were more strongly affected by habitat characteristics, namely by insolation and soil characteristics. Local species richness of diplopods depended almost entirely on the surrounding landscape. In general, the composition of the neighbouring landscape had a lower impact on the species richness of most soil macroarthropod taxa than did land use and habitat characteristics. Main conclusions We conclude that agri‐environment schemes for the conservation of biodiversity in cultivated landscapes have to secure management for both habitat quality and heterogeneous landscape mosaics.     

Long-Term Impacts of Fuelwood Extraction on a Tropical Montane Cloud Forest

Fuelwood extracted from natural forests serves as a principal energy source in rural regions of many tropical countries. Although fuelwood extraction (even low intensities) might strongly impact the structure and species composition of natural forests, long-term studies remain scarce. Here, we estimate the potential long-term impacts (over several hundred years) of such repeated harvesting of single trees on tropical montane cloud forest in central Veracruz, Mexico, by applying a process-based forest growth model. We simulate a wide range of possible harvesting scenarios differing in wood volume harvested and preferred tree species and sizes, and use a set of indicators to compare their impacts on forest size structure and community composition. Results showed that the overall impact on forest structure and community composition increased linearly with the amount of harvested wood volume. Even at low levels of harvesting, forest size structure became more homogeneous in the long term because large old trees disappeared from the forest, but these changes might take decades or even centuries. Although recruitment of harvested species benefited from harvesting, species composition shifted to tree species that are not used for fuelwood. Our results demonstrate that fuelwood extraction can have marked long-term impacts on tropical montane cloud forests. The results also offer the possibility to support the design of management strategies for the natural species-rich forests that achieve a balance between economic needs and ecological goals of the stakeholders. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.