Des premières amours aux secondes

Bien qu’Ernst Haeckel soit surtout connu comme zoologiste, il fit ses débuts scientifiques en botanique. Cet aspect de sa biographie scientifique est très méconnu. À la lumière du projet « Ernst Haeckel (1843-1919) : édition de la correspondance », les débuts de Haeckel en botanique ont suscité une attention croissante. Des lettres et journaux personnels inédits, ainsi que son herbier méconnu et deux articles de jeunesse, démontrent que la botanique joua un rôle déterminant dans sa formation de 1840 à 1854. Sous l’influence de Johannes Müller, il prit ensuite la décision de faire carrière dans la zoologie. Mais son amour des plantes ne disparut jamais complètement. On examine ici en profondeur le déroulement des études botaniques de Haeckel, on montre que les plantes tinrent une grande place dans les études naturalistes du jeune Haeckel et on pose la question des raisons de sa réorientation zoologique. Haeckel continua à collecter des plantes lors de ses divers voyages, sans même que cela fût dans un but scientifique. Sa botanique devint pour une bonne part une activité esthétique, donnant lieu à de nombreux dessins et à de vives descriptions de plantes, notamment tropicales. Ajoutés à son important herbier, ils donnent une image impressionnante des activités botaniques de Haeckel.Though Ernst Haeckel was mostly known as a zoologist, he started off into science with botany. This aspect of his scientific biography has been largely underrated. In the light of the ongoing project “Ernst Haeckel (1834-1919): Edition of Letters”, Haeckel’s early botanical beginnings have attracted increased attention. Hitherto unpublished letters and diaries, including his hardly known herbarium, and two early essays, support the view that botany played a pivotal role in his formal training from 1840 to 1854. Under the influence of Johannes Müller, he first decided to pursue his scientific career as a zoologist. But his love for plants never left him completely. The course of Haeckel’s botanical studies will be explored in more detail below. It will be shown that plants formed a substantial part of the young Haeckel’s occupation with nature. The probable reasons for his zoological turn will be discussed. Haeckel continued collecting plants on his various travels, though without any scientific ambitions. Botany largely turned into an aesthetic enterprise, giving rise to numerous paintings and vivid descriptions of plants, especially those from the tropics. Together with his large herbarium, they provide an impressive picture of Haeckel’s botanical activities

In vivo 1H-magnetic resonance spectroscopy can detect metabolic changes in APP/PS1 mice after donepezil treatment

<p>Abstract</p> <p>Background</p> <p>Donepezil improves cognitive functions in AD patients. Effects on the brain metabolites N-acetyl-L-aspartate, choline and <it>myo-</it>inositol levels have been reported in clinical studies using this drug. The APP/PS1 mouse coexpresses the mutated forms of human β-amyloid precursor protein (APP) and mutated human presenilin 1 (PS1). Consequently, the APP/PS1 mouse model reflects important features of the neurochemical profile in humans. <it>In vivo </it>magnetic resonance spectroscopy (¹H-MRS) was performed in fronto-parietal cortex and hippocampus (ctx/hipp) and in striatum (str). Metabolites were quantified using the LCModel and the final analysis was done using multivariate data analysis. The aim of this study was to investigate if multivariate data analysis could detect changes in the pattern of the metabolic profile after donepezil treatment.</p> <p>Results</p> <p>Significant differences were observed in the metabolic pattern of APP/PS1 mice in both str and ctx/hipp before and after donepezil treatment using multivariate data analysis, evidencing a significant treatment effect. A treatment effect was also seen in wild type (wt) mice in str. A significant decrease in the metabolic ratio taurine/creatine (Tau/tCr) was related to donepezil treatment (p < 0.05) in APP/PS1 mice in both brain regions. Furthermore, a significant influence on the choline/creatine (tCho/tCr) level was observed in treated APP/PS1 mice compared to untreated in str (p = 0.011). Finally, there was an increase in glutamate/creatine (Glu/tCr) in str in wt mice treated with donepezil.</p> <p>Conclusion</p> <p>Multivariate data analysis can detect changes in the metabolic profile in APP/PS1 mice after donepezil treatment. Effects on several metabolites that are measurable <it>in vivo </it>using MR spectroscopy were observed. Changes in Tau/tCr and tCho/tCr could possibly be related to changed cholinergic activity caused by donepezil treatment.</p

The use of Stokes-Mueller polarimetry for assessment of amyloid-β progression in a mouse model of Alzheimer's disease

Alzheimer's disease, being a major societal burden, demands improvement of current techniques for its treatment and diagnostics. Currently only autopsy histology is able to provide the definite diagnosis for Alzheimer's disease. However, the procedure is rather time consuming and costly. In the current study, we utilized Stokes and Mueller polarimetry techniques to screen for amyloid-β (Aβ) deposits in formalin-fixed, paraffin-embedded mouse brain tissue at different stages of Alzheimer's disease. The study has shown that the presence of Aβ plaques influences the properties of scattered polarized light. The Poincaré sphere was used as a graphical tool for the visualization of the alterations of the Stokes vector, obtained with Stokes polarimetry, whereas statistical moments were used for the analysis of depolarization distributions that were acquired with Mueller polarimetry. We demonstrate the sensitivity of the last component of the Stokes vector, the degree of polarization and high-order statistical moments of depolarization to the structural alterations in brain tissue, which correspond to the disease progression. The described approach has a potential to improve the existing pathology screening methods and facilitates Aβ detection in AD research

Evaluating β-amyloidosis progression in Alzheimer’s disease with Mueller polarimetry

We applied the wide-field Mueller imaging polarimetry for the screening of formalin-fixed paraffin-embedded samples of mouse brain tissue at different stages of brain β-amyloidosis in Alzheimer’s disease (AD). The accumulation of amyloid-beta (Aβ) deposits throughout the brain tissue is one of the key pathological hallmarks observed with the AD progression. We demonstrate that the presence of Aβ plaques influences the properties of backscattered polarized light, in particular, its degree of depolarization. By means of statistical analysis, we demonstrate that the high-order statistical moments of depolarization distributions, acquired with the multi-spectral Mueller imaging polarimetry, can be used as sensitive markers of the growing presence of Aβ plaques. The introduced label-free polarimetric approach has a potential to facilitate the current practice of the histopathology screening in terms of diagnosis accuracy, time and cost efficiency

Strategies to gain novel Alzheimer’s disease diagnostics and therapeutics using modulators of ABCA transporters

Adenosine-triphosphate-(ATP)-binding cassette (ABC) transport proteins are ubiquitously present membrane-bound efflux pumps that distribute endo- and xenobiotics across intra- and intercellular barriers. Discovered over 40 years ago, ABC transporters have been identified as key players in various human diseases, such as multidrug-resistant cancer and atherosclerosis, but also neurodegenerative diseases, such as Alzheimer’s disease (AD). Most prominent and well-studied are ABCB1, ABCC1, and ABCG2, not only due to their contribution to the multidrug resistance (MDR) phenotype in cancer, but also due to their contribution to AD. However, our understanding of other ABC transporters is limited, and most of the 49 human ABC transporters have been largely neglected as potential targets for novel small-molecule drugs. This is especially true for the ABCA subfamily, which contains several members known to play a role in AD initiation and progression. This review provides up-to-date information on the proposed functional background and pathological role of ABCA transporters in AD. We also provide an overview of small-molecules shown to interact with ABCA transporters as well as potential in silico, in vitro, and in vivo methodologies to gain novel templates for the development of innovative ABC transporter-targeting diagnostics and therapeutics

Uptake of 18F-fluorocholine, 18F-fluoro-ethyl- L -tyrosine and 18F-fluoro-2-deoxyglucose in F98 gliomas in the rat

Introduction: The positron emission tomography (PET) tracers 18F-fluoro-ethyl-L-tyrosine (FET), 18F-fluorocholine (N,N-dimethyl-N-[18F]fluoromethyl-2-hydroxyethylammonium (FCH]) and 18F-fluoro-2-deoxyglucose (FDG) are used in the diagnosis of brain tumours. The aim of this study was threefold: (a) to assess the uptake of the different tracers in the F98 rat glioma, (b) to evaluate the impact of blood-brain barrier (BBB) disruption and microvessel density (MVD) on tracer uptake and (c) to compare the uptake in the tumours to that in the radiation injuries (induced by proton irradiation of healthy rats) of our previous study. Methods: F98 gliomas were induced in 26 rats. The uptake of FET, FCH and FDG was measured using autoradiography and correlated with histology, disruption of the BBB and MVD. Results: The mean FET, FCH and FDG standardised uptake values (SUVs) in the tumour and the contralateral normal cortex (in parentheses) were 4.19±0.86 (1.32±0.26), 2.98±0.58 (0.51±0.11) and 11.02±3.84 (4.76±1.77) respectively. MVD was significantly correlated only with FCH uptake. There was a trend towards a negative correlation between the degree of BBB disruption and FCH uptake and a trend towards a positive correlation with FET uptake. The ratio of the uptake in tumours to that in the radiation injuries was 1.97 (FCH), 2.71 (FET) and 2.37 (FDG). Conclusion: MVD displayed a significant effect only on FCH uptake. The degree of BBB disruption seems to affect the accumulation of FET and FCH, but not FDG. Mean tumour uptake for all tracers was significantly higher than the accumulation in radiation injurie

The choroid plexus in health and in disease: dialogues into and out of the brain

This article brings the choroid plexus into the context of health and disease. It is remarkable that the choroid plexus, composed by a monolayer of epithelial cells that lie in a highly vascularized stroma, floating within the brain ventricles, gets so little attention in major physiology and medicine text books and in the scientific literature in general. Consider that it is responsible for producing most of the about 150 mL of cerebrospinal fluid that fills the brain ventricles and the subarachnoid space and surrounds the spinal cord in the adult human central nervous system, which is renewed approximately 2-3 times daily. As such, its activity influences brain metabolism and function, which will be addressed. Reflect that it contains an impressive number of receptors and transporters, both in the apical and basolateral sides of the epithelial cells, and as such is a key structure for the communication between the brain and the periphery. This will be highlighted in the context of neonatal jaundice, multiple sclerosis and Alzheimer's disease. Realize that the capillaries that irrigate the choroid plexus stroma do not possess tight junctions and that the blood flow to the choroid plexus is five times higher than that in the brain parenchyma, allowing for a rapid sensing system and delivery of molecules such as nutrients and metals as will be revised. Recognize that certain drugs reach the brain parenchyma solely through the choroid plexus epithelia, which has potential to be manipulated in diseases such as neonatal jaundice and Alzheimer's disease as will be discussed. Without further notice, it must be now clear that understanding the choroid plexus is necessary for comprehending the brain and how the brain is modulated and modulates all other systems, in health and in disease. This review article intends to address current knowledge on the choroid plexus, and to motivate the scientific community to consider it when studying normal brain physiology and diseases of the central nervous system. It will guide the reader through several aspects of the choroid plexus in normal physiology, in diseases characteristic of various periods of life (newborns-kernicterus, young adults-multiple sclerosis and the elder Alzheimer's disease), and how sex-differences may relate to disease susceptibility.The work at ICVS/3B's has the support of Portuguese North Regional Operational Program (ON.2 – O Novo Norte) under the National Strategic Reference Framework (QREN), through the European Regional Development Fund (FEDER). JCS, FM and JAP have the support of a fellowship from Bial Foundation through Grant 217/12. Fernanda Marques is a recipient of a FCT Investigator award (IF/ 00231/2013) of the Fundação para a Ciência e Tecnologia (FCT, Portugal). The work by JP has been financed by the following grants: Deutsche Forschungsgemeinschaft DFG PA930/9, DFG PA930/12; VIAA Latvia NFI/ R/2014/023; Leibniz Society SAW-2015-IPB-2; HelseSØ No: 2016062; Norsk forskningsrådet: NFR251290, NFR246392, NFR248772, JPND NeuroGEM NFR247179, JPND PROP-AD NFR260786. The work by CS has been supported by the Portuguese Foundation for Science and Technology (FCT, Portugal – hrrp://www.fct.pt) project grants (PTDC/SAU-NEU/114800/2009); and by FEDER funds through the POCI - COMPETE 2020 - Operational Programme Competitiveness and Internationalisation in Axis I - Strengthening research, technological development and innovation (Project No. 007491) and National Funds by FCT - Foundation for Science and Technology (Project UID/ Multi/00709). The work by AB at Faculty of Pharmacy, Universidade de Lisboa, was funded, in part, by iMed.ULisboa (UID/DTP/04138/2013) from Fundação para a Ciência e a Tecnologia (FCT), Portugal.info:eu-repo/semantics/publishedVersio

Expressionview: visualization of quantitative trait loci and gene-expression data in Ensembl

We present here a software tool for combined visualization of gene-expression data and quantitative trait loci (QTL). The application is implemented as an extension to the Ensembl project and caters for a direct transition from microarray experiments of gene or protein expression levels to the genomic context of individual genes and QTL. It supports the visualization of gene clusters and the selection of functional candidate genes in the context of research on complex traits

Screening of Alzheimer’s disease with multiwavelength Stokes polarimetry in a mouse model

The minimum histological criterion for the diagnostics of Alzheimer’s disease (AD) in tissue is the presence of senile plaques and neurofibrillary tangles in specific brain locations. The routine procedure of morphological analysis implies time-consuming and laborious steps including sectioning and staining of formalin-fixed paraffin-embedded (FFPE) tissue. We developed a multispectral Stokes polarimetric imaging approach that allows characterization of FFPE brain tissue samples to discern the stages of AD progression without sectioning and staining the tissue. The Stokes polarimetry approach is highly sensitive to structural alterations of brain tissue, particularly to the changes in light scattering and birefringence. We present the results of the label-free non-destructive screening of FFPE mouse brain tissue and show several polarization metrics that demonstrate statistically significant differences for tissues at different stages of AD

Isotope‐labeled amyloid‐β does not transmit to the brain in a prion‐like manner after peripheral administration

Findings of early cerebral amyloid-β deposition in mice after peripheral injection of amyloid-β-containing brain extracts, and in humans following cadaveric human growth hormone treatment raised concerns that amyloid-β aggregates and possibly Alzheimer’s disease may be transmissible between individuals. Yet, proof that Aβ actually reaches the brain from the peripheral injection site is lacking. Here, we use a proteomic approach combining stable isotope labeling of mammals and targeted mass spectrometry. Specifically, we generate 13C-isotope-labeled brain extracts from mice expressing human amyloid-β and track 13C-lysine-labeled amyloid-β after intraperitoneal administration into young amyloid precursor protein-transgenic mice. We detect injected amyloid-β in the liver and lymphoid tissues for up to 100 days. In contrast, injected 13C-lysine-labeled amyloid-β is not detectable in the brain whereas the mice incorporate 13C-lysine from the donor brain extracts into endogenous amyloid-β. Using a highly sensitive and specific proteomic approach, we demonstrate that amyloid-β does not reach the brain from the periphery. Our study argues against potential transmissibility of Alzheimer’s disease while opening new avenues to uncover mechanisms of pathophysiological protein deposition.Peer reviewe