Multiplex LA-ICP-MS bio-imaging of brain tissue of a parkinsonian mouse model stained with metal-coded affinity-tagged antibodies and coated with indium-spiked commercial inks as internal standards

SH received financial support by the “Bundesministerium fuer Wirtschaft und Energie, Projektnummer MNPQ 09/10″.Peer reviewedPublisher PD

Solubility of α-synuclein species in the L62 mouse model of synucleinopathy

The authors acknowledge Dr. Silke Frahm for providing the 4D6 immunoblot in Supplementary Fig. S1.Peer reviewe

Endothelin-1 overexpression and endothelial nitric oxide synthase knock-out induce different pathological responses in the heart of male and female mice

AbstractAimsThe nitric oxide and endothelin systems are key components of a local paracrine hormone network in the heart. We previously reported that diastolic dysfunction observed in mice lacking the endothelial nitric oxide synthase (eNOS−/−) can be prevented by a genetic overexpression of ET-1. Sexual dimorphisms have been reported in both ET-1 and NO systems. Particularly, eNOS−/− mice present sex related phenotypic differences.Main methodsWe used the ET-1 transgenic (ET+/+), eNOS−/−, and crossbred ET+/+eNOS−/− mice, and wild type controls. We measured cardiac function by heart catheterization. Cardiac ventricles were collected for histological and molecular profiling.Key findingsWe report here that (i) the level of ET-1 expression in eNOS−/− mice was elevated in males but not in females. (ii) Left ventricular end-diastolic blood pressure was higher in male eNOS−/− mice than in females. (ii) eNOS−/− males but not females developed cardiomyocyte hypertrophy. (iv) Perivascular fibrosis of intracardiac arteries developed in female ET+/+ and eNOS−/− mice but not in males. Additionally, (v) the cardiac expression of metalloprotease-9 was higher in eNOS−/− males compared to females. Finally, (vi) cardiac proteome analysis revealed that the protein abundance of the oxidative stress related enzyme superoxide dismutase presented with sexual dimorphism in eNOS−/− and ET+/+ mice.SignificanceThese results indicate that the cardiac phenotypes of ET-1 transgenic mice and eNOS knockout mice are sex specific. Since both systems are key players in the pathogenesis of cardiovascular diseases, our findings might be important in the context of gender differences in patients with such diseases

Studies on Acanthocheilonema viteae cystatin: Genomic organization, promoter studies and expression in Caenorhabditis elegans

Cystatins are reversible, tightly binding inhibitors of cysteine proteases. Filarial cystatins have been ascribed immunomodulatory properties and have been implicated in protective immunity. To continue exploration of this potential, here we have determined the sequence, structure and genomic organization of the cystatin gene locus of A. viteae. The gene is composed of 4 exons separated by 3 introns and spans ~2 kb of genomic DNA. The upstream genomic sequence contains transcriptional factor binding sites such as AP-1 and NF-Y, an inverted CCAAT sequence, and a TATA box. To investigate sites of cystatin expression, Caenorhabditis elegans worms were transformed by microinjection with the putative promoter region and the first exon of the A. viteae cystatin gene fused to the reporter GFP. In transgenic worms fluorescence was observed in the pharyngeal and rectal gland cells suggesting that cystatin is secreted. Additionally, A. viteae cystatin was expressed in C. elegans to explore its potential as an expression system for filarial genes

Proteomic analysis of hydromethylthionine in the line 66 model of frontotemporal dementia demonstrates actions on tau-dependent and tau-independent networks

Funding: This research received no external funding. Acknowledgments: The authors acknowledge Boris Neumann and Karola Lehmann for the excellent support with the proteomics data.Peer reviewedPublisher PD

Glutamatergic transmission and receptor expression in the synucleinopathy h-α-synL62 mouse model : Effects of hydromethylthionine

Acknowledgements The authors acknowledge Dr. Dilyara Lauer and Heide Lueck for the excellent technical support with the administration of drugs, collection of brains and sectioning of brain tissue for immunohistochemistry. Funding This work was funded by TauRx Therapeutics Ltd., Singapore. Z. C. was funded by the Erasmus+ programme of the European Union.Peer reviewedPublisher PD

Cholinergic and inflammatory phenotypes in transgenic tau mouse models of Alzheimer’s Disease and Frontotemporal Lobar Degeneration

All authors have made a substantial, direct and intellectual contribution to the work, and approved it for publication. This work was funded by NCN grant 2014/15/B/NZ4/05041 and WisTa Laboratories Ltd. CH and CW serve as officers in both WisTa Laboratories Ltd. and TauRx Therapeutics Ltd. The sponsor was involved in the design of the study; in the collection, analysis and interpretation of data; and in the writing of the report. The corresponding authors had full access to all the data and had final responsibility for submission of the report for publication.Peer reviewedPublisher PD

Differential compartmental processing and phosphorylation of pathogenic human tau and native mouse tau in the Line 66 model of frontotemporal dementia

Funding Information: Funding and additional information—This work was supported by EMPIR programme in Research Project 15HLT02 ReMiND cofinanced by the Participating States and the European Union's Horizon 2020 research and innovation programme (to N. L.). Work was also supported by WisTa Laboratories Ltd. (to V. M., D. L., M. M., C. R. H., G. R., C. M. W., F. T., and K. S.). Conflict of interest—This work was sponsored by WisTa Laboratories Ltd., an affiliate of TauRx Therapeutics Ltd. C. R. H. and C. M. W. are employees and officers of TauRx Therapeutics Ltd.Peer reviewedPublisher PD

Cu, Fe, and Zn isotope ratios in murine Alzheimer's disease models suggest specific signatures of amyloidogenesis and tauopathy

Acknowledgments—A.H.E-K thanks Maren Koenig and Dorit Becker for their support in sample preparation. The authors thank Prof. Gernot Riedel, Dr Silke Frahm, and Mandy Magbagbeolu for help with mouse perfusion and harvesting of the brain tissues. Funding and additional information—This work was carried out in the context of the EMPIR research project 15HLT02 (ReMiND). This project has received funding from the EMPIR programme cofinanced by the Participating States and from the European Union’s Horizon 2020 research and innovation program.Peer reviewedPublisher PD

Increased Cholinergic Response in α-Synuclein Transgenic Mice (h-α-synL62)

Peer reviewedPostprin