Suchergebnisse

Background: Vagus nerve stimulation (VNS) using non-invasive approaches have attracted great attention due to their anti-epileptic, anti-depressive and pro-cognitive effects. It has been proposed that auricular transcutaneous VNS (atVNS) could benefit intellectual disability disorders, but preclinical data supporting this idea is limited. Objective: To develop an atVNS device for mice and to test its efficacy on memory performance in naïve mice and in a mouse model for intellectual disability. Methods: Naïve outbreed CD-1 mice and a model for fragile X syndrome, the Fmr1 knockout (Fmr1KO), were used to assess the effect of atVNS in the novel object-recognition memory performance. Results: We found that atVNS significantly improves memory persistence in naïve mice. Notably, atVNS was efficacious in normalizing the object-recognition memory deficit in the Fmr1KO model. Conclusion: Our data show that atVNS improves memory persistence in naïve mice and in a model of intellectual disability and support further studies taking advantage of preclinical mouse models of cognitive disorders. ; This work was supported by a Predoctoral fellowship from Jerome Lejeune Foundation (Spanish division) (A.V.-O.) and from "la Caixa" Foundation (ID 100010434), LCF/BQ/IN18/11660012 and European Union's Horizon 2020 research and innovation programme under the Marie Slodowska-Curie grant agreement No. 713673 (C.B.-P.). Ministerio de Economía, Innovación y Competitividad (MINECO) [#RTI2018-099282-B-I00 to A.O., #SAF2017-84060-R to R.M.]; the Instituto de Salud Carlos III [#RD16/0017/0020 to R.M.]; the Generalitat de Catalunya [2017SGR-669 to R.M.]; the ICREA (Institució Catalana de Recerca i Estudis Avançats) Acadèmia to A.O., A.I. and R.M.; Grant "Unidad de Excelencia María de Maeztu", funded by the MINECO [#MDM-2014-0370]; PLAN E (Plan Español para el Estímulo de la Economía y el Empleo). FEDER (Fondo Europeo de Desarrollo Regional) funding is also acknowledged

Acknowledgments We thank Steffen Ruehlow, Agnes Fastnacht, Karl Kuebler, Iris Kuhlmann, Heike Geilmann, and Petra Linke for technical support in establishing the experiment and with stable isotope analyses. We also thank Markus Lange, Daniel Read, and Hyun Gweon for helpful discussions. Funding AM has received funding from Max Planck Society and the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 655240. AM has also received a career orientation grant from the Jena School for Microbial Communication (JSMC) that funded the laboratory visits. DFG SFB Aquadiva funded part of this work. ; Peer reviewed ; Publisher PDF

Risks posed to bees from neonicotinoid seed treatments (clothianidin, thiamethoxam, imidacloprid) led in 2013 to the European Union instigating a moratorium for their use on mass-flowering crops, including oilseed rape in the UK. This restriction did allow for the continued use of these seed treatments, in particular clothianidin, on non-flowering crops like winter wheat. To determine the impacts of the moratorium, we assessed neonicotinoid concentrations pre- (2014) and post- (2015−17) moratorium in 347 honey samples collected across Great Britain. While the probability of detecting clothianidin declined immediately following the moratorium, detection rates remained constant over the following three years (mean = 0.10 ppb, maximum = 2.8 ppb). In contrast, after three years thiamethoxam residues entirely disappeared while detection of imidacloprid was infrequent but persistent over the whole period. For those hives where neonicotinoids were detected, there was no evidence that the concentrations in the honey declined over the three years following the ban. Using metabarcoding approaches, we identified plants foraged upon by honeybees during the production of honey. After the moratorium came into effect, the highest neonicotinoid residues were associated with honey produced by foraging on both oilseed rape and several wild plants found in arable field margins. Concerns about soil persistence and uptake by non-target flowering plants ultimately led to a full European Union ban in 2018. Our results suggest that before this full ban came into effect, the use of clothianidin on non-flowering crops maintained a low-level probability of encountering this neonicotinoid within honey. However, these concentrations were low and would have been unlikely to pose significant risks to honeybees.

This study was supported by the UK Natural Environment Research Council (NE/H019456/1) to CJvdG, by the Wellcome Trust (WT 098051) to AWW and JP for sequencing costs, and by The Anna Trust (KB2008) to KDB. AWW and The Rowett Institute of Nutrition and Health, University of Aberdeen, receive core funding support from the Scottish Government Rural and Environmental Science and Analysis Service (RESAS). We thank Paul Scott, Richard Rance and the Wellcome Trust Sanger Institute's sequencing team for generating 16S rRNA gene sequence data. ; Peer reviewed ; Publisher PDF

We thank the patients and staff at each of the contributing centres for their involvement, time and patience in sample collection. This study was supported by grants from the UK Natural Environment Research Council (NE/H019456/1) and the Wellcome Trust (WT 098051). AWW receives core funding support from the Scottish Government's Rural and Environment Science and Analytical Services (RESAS) division. AA and GO received support from the Dartmouth Translational Research Core (CFF RDP STANTO15R0) for acquiring samples. ; Peer reviewed ; Publisher PDF