Of adenosine and the blues: the adenosinergic system in the pathophysiology and treatment of major depressive disorder

© 2020 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Major depressive disorder (MDD) is the foremost cause of global disability, being responsible for enormous personal, societal, and economical costs. Importantly, existing pharmacological treatments for MDD are partially or totally ineffective in a large segment of patients. As such, the search for novel antidepressant drug targets, anchored on a clear understanding of the etiological and pathophysiological mechanisms underpinning MDD, becomes of the utmost importance. The adenosinergic system, a highly conserved neuromodulatory system, appears as a promising novel target, given both its regulatory actions over many MDD-affected systems and processes. With this goal in mind, we herein review the evidence concerning the role of adenosine as a potential player in pathophysiology and treatment of MDD, combining data from both human and animal studies. Altogether, evidence supports the assertions that the adenosinergic system is altered in both MDD patients and animal models, and that drugs targeting this system have considerable potential as putative antidepressants. Furthermore, evidence also suggests that modifications in adenosine signaling may have a key role in the effects of several pharmacological and non-pharmacological antidepressant treatments with demonstrated efficacy, such as electroconvulsive shock, sleep deprivation, and deep brain stimulation. Lastly, it becomes clear from the available literature that there is yet much to study regarding the role of the adenosinergic system in the pathophysiology and treatment of MDD, and we suggest several avenues of research that are likely to prove fruitful.This work was supported by project funding from Fundação para a Ciência e para a Tecnologia (FCT) to SHV (PTDC/BTM-SAL/32147/2017) and AMS (PTDC/MED-FAR/30933/2017). This project has received funding from H2020-WIDESPREAD-05-2017-Twinning (EpiEpinet) under grant agreement No. 952455. MF-F (SFRH/BD/147505/2019), JG-R (PD/BD/150342/2019), and NR (PD/BD/113463/2015) are supported by PhD fellowships from FCT.info:eu-repo/semantics/publishedVersio

Relación entre Medidas Zoométricas en Vacas Holstein-Friesian y Dimensiones de Cubículos en Granjas Lecheras

Body measurements in Portuguese Holstein-Friesian breed and its association with the dimensions of the cubicles were investigated. During a period of 5 months, body measurements and cubicles size data from 55 commercial Portuguese dairy herds were collected including in total 1054 individual cows. Data were analyzed using the general linear model and principal components. The most relevant body measurements were: height at withers (141.1±4.72 cm), height at rump (144.2±4.47 cm), length of trunk (170.8±8.31 cm), width of biiliac (55.9±4.17 cm) and perimeter of the thorax (206.8±10.43 cm). In general, the first class of parity showed significant different measures (P<0.001) associated with the development of animals. Head to head cubicle length and cubicle width were 223.0±11.0 cm and 113.0±5.0 cm respectively; whereas in cubicle against wall length was 227.0±18.0 cm and width 111.0±7.0 cm. The highest correlations were found for body measures between the different heights and between the height at chest and perimeter of the thorax. The analysis showed no relation between body measurements and dimensions of the cubicles. Principal component analysis of the different body measurements and cubicles dimensions expressed 51.4% of the total variability, in which the first factor represented 40.2% and the second factor 11.1%.info:eu-repo/semantics/publishedVersio

Going the extra (synaptic) mile: excitotoxicity as the road toward neurodegenerative diseases

Copyright © 2020 Armada-Moreira, Gomes, Pina, Savchak, Gonçalves-Ribeiro, Rei, Pinto, Morais, Martins, Ribeiro, Sebastião, Crunelli and Vaz. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Excitotoxicity is a phenomenon that describes the toxic actions of excitatory neurotransmitters, primarily glutamate, where the exacerbated or prolonged activation of glutamate receptors starts a cascade of neurotoxicity that ultimately leads to the loss of neuronal function and cell death. In this process, the shift between normal physiological function and excitotoxicity is largely controlled by astrocytes since they can control the levels of glutamate on the synaptic cleft. This control is achieved through glutamate clearance from the synaptic cleft and its underlying recycling through the glutamate-glutamine cycle. The molecular mechanism that triggers excitotoxicity involves alterations in glutamate and calcium metabolism, dysfunction of glutamate transporters, and malfunction of glutamate receptors, particularly N-methyl-D-aspartic acid receptors (NMDAR). On the other hand, excitotoxicity can be regarded as a consequence of other cellular phenomena, such as mitochondrial dysfunction, physical neuronal damage, and oxidative stress. Regardless, it is known that the excessive activation of NMDAR results in the sustained influx of calcium into neurons and leads to several deleterious consequences, including mitochondrial dysfunction, reactive oxygen species (ROS) overproduction, impairment of calcium buffering, the release of pro-apoptotic factors, among others, that inevitably contribute to neuronal loss. A large body of evidence implicates NMDAR-mediated excitotoxicity as a central mechanism in the pathogenesis of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), and epilepsy. In this review article, we explore different causes and consequences of excitotoxicity, discuss the involvement of NMDAR-mediated excitotoxicity and its downstream effects on several neurodegenerative disorders, and identify possible strategies to study new aspects of these diseases that may lead to the discovery of new therapeutic approaches. With the understanding that excitotoxicity is a common denominator in neurodegenerative diseases and other disorders, a new perspective on therapy can be considered, where the targets are not specific symptoms, but the underlying cellular phenomena of the disease.This work was funded by Fundação para a Ciência e Tecnologia (FCT), Portugal (PTDC/BTM-SAL/32147/2017, PD/BD/114278/2016, IMM/BI/2-2020), and by FCT/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado (UID/BIM/50005/2019). TM was funded by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska/Curie grant agreement No. 722053.info:eu-repo/semantics/publishedVersio

Progress in analytical approaches integrating Livestock and Biodiversity to identify HNV Montados

The World Congress Silvo-Pastoral Systems 2016 aims to gather researchers from different disciplines, practitioners and policy makers at different governance levels that deal with the management and sustainability of silvo-pastoral systems. In this way the congress will create a fertile context to progress through interdisciplinarity research approaches that can help translate scientific knowledge into new adaptive management solutions, and thus bridge from science to practice. The aim is also to gather and compare knowledge from silvo-pastoral systems around the world, which share drought as a limiting factor, so that they can be discussed and evaluated

Effects of Topically Administered Neuroprotective Drugs in Early Stages of Diabetic Retinopathy:Results of the EUROCONDOR Clinical Trial

The primary objective of this study was to assess whether the topical administration of two neuroprotective drugs (brimonidine and somatostatin) could prevent or arrest retinal neurodysfunction in patients with type 2 diabetes. For this purpose, adults aged between 45 and 75 years with a diabetes duration ≥5 years and an Early Treatment of Diabetic Retinopathy Study (ETDRS) level of ≤35 were randomly assigned to one of three arms: placebo, somatostatin, or brimonidine. The primary outcome was the change in implicit time (IT) assessed by multifocal electroretinography between baseline and at the end of follow-up (96 weeks). There were 449 eligible patients allocated to brimonidine (n = 152), somatostatin (n = 145), or placebo (n = 152). When the primary end point was evaluated in the whole population, we did not find any neuroprotective effect of brimonidine or somatostatin. However, in the subset of patients (34.7%) with preexisting retinal neurodysfunction, IT worsened in the placebo group (P < 0.001) but remained unchanged in the brimonidine and somatostatin groups. In conclusion, the topical administration of the selected neuroprotective agents appears useful in preventing the worsening of preexisting retinal neurodysfunction. This finding points to screening retinal neurodysfunction as a critical issue to identify a subset of patients in whom neuroprotective treatment might be of benefit

The national inventory of geological heritage: methodological approach and results

A existência de um inventário nacional de património geológico é fundamental para se poderem implementar estratégias de geoconservação. Este trabalho apresenta a metodologia usada no desenvolvimento do mais completo inventário de geossítios, realizado até ao momento em Portugal, assim como os principais resultados obtidos. O inventário vai integrar o Sistema de Informação do Património Natural e o Cadastro Nacional dos Valores Naturais Classificados, ambos geridos pelo Instituto de Conservação da Natureza e da Biodiversidade.The existence of a national inventory of the geological heritage is of paramount importance for the implementation of a geoconservation strategy. This paper presents the methodological approach used to produce the most complete geosites inventory in Portugal, so far, and the obtained results. This inventory will be uploaded into the National Database of Natural Heritage managed by the Portuguese authority for nature conservation.Este trabalho é apoiado pela Fundação para a Ciência e a Tecnologia, através do financiamento plurianual do CGUP e do projecto de investigação “Identificação, caracterização e conservação do património geológico: uma estratégia de geoconservação para Portugal” (PTDC/CTE-GEX/64966/2006).info:eu-repo/semantics/publishedVersio

description of the methodological approach

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