Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors

© 1998 Society for NeuroscienceATP analogs substituted in the γ-phosphorus (ATPγS, β, γ-imido-ATP, and β, γ-methylene-ATP) were used to probe the involvement of P2 receptors in the modulation of synaptic transmission in the hippocampus, because their extracellular catabolism was virtually not detected in CA1 slices. ATP and γ-substituted analogs were equipotent to inhibit synaptic transmission in CA1 pyramid synapses (IC50 of 17–22 μM). The inhibitory effect of ATP and γ-phosphorus-substituted ATP analogs (30 μM) was not modified by the P2 receptor antagonist suramin (100 μM), was inhibited by 42–49% by the ecto-5’- nucleotidase inhibitor and α, β-methylene ADP (100 μM), was inhibited by 74–85% by 2 U/ml adenosine deaminase (which converts adenosine into its inactive metabolite-inosine), and was nearly prevented by the adenosine A1 receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (10 nM). Stronger support for the involvement of extracellular adenosine formation as a main requirement for the inhibitory effect of ATP and γ-substituted ATP analogs was the observation that an inhibitor of adenosine uptake, dipyridamole (20 μM), potentiated by 92–124% the inhibitory effect of ATP and γ-substituted ATP analogs (10 μM), a potentiation similar to that obtained for 10 μM adenosine (113%). Thus, the present results indicate that inhibition by extracellular ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ectonucleotidases and channeling of the generated adenosine to adenosine A1 receptors.This work was supported by Junta Nacional de Investigação Cientifica e Tecnológica, Praxis XXI, Gulbenkian Foundation, and European Union (BIOMED 2 programme

Caffeine and adenosine

© 2010 – IOS Press and the authors. All rights reservedCaffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Besides AR antagonism, xanthines, including caffeine, have other biological actions: they inhibit phosphodiesterases (PDEs) (e.g., PDE1, PDE4, PDE5), promote calcium release from intracellular stores, and interfere with GABA-A receptors. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, Epilepsy, Pain/Migraine, Depression, Schizophrenia. In conclusion, targeting approaches that involve ARs will enhance the possibilities to correct brain dysfunctions, via the universally consumed substance that is caffeine.The work in the authors’ laboratory is supported by research grants from Fundação para a Ciência e Tecnologia (FCT), Gulbenkian Foundation and European Union (COST B30)

Strategy to evaluate the stress-crack opening relationship of the SFRC

No presente trabalho é descrita a metodologia desenvolvida para a determinação dos parâmetros de fractura do betão reforçado com fibras de aço, designadamente, a forma da relação tensão-abertura de fenda e a energia subjacente ao processo de fendilhação deste compósito. Para tal recorreu-se a resultados experimentais obtidos em ensaios de flexão efectuados segundo as recomendações do TC 162-TDF da RILEM e foram desenvolvidos dois modelos numéricos, um com base num modelo de secção e o outro utilizando elementos finitos de interface para modelar a progressão da fenda.The methodology developed to determine the fracture parameters of the steel fibre reinforced concrete is described in the present work. The shape of the stress-crack opening displacement relationship and the fracture energy were assessed. For this purpose, the forcedeflection relationships obtained in experimental tests carried out according to the recommendations of the RILEM TC 162-TDF were taken and two numerical approaches were developed, one based on the cross-section layer model and the other using interface finite elements to model the crack opening propagation

Amyotrophic Lateral Sclerosis ALS and adenosine receptors

Copyright © 2018 Sebastião, Rei and Ribeiro. 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 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.In the present review we discuss the potential involvement of adenosinergic signaling, in particular the role of adenosine receptors, in amyotrophic lateral sclerosis (ALS). Though the literature on this topic is not abundant, the information so far available on adenosine receptors in animal models of ALS highlights the interest to continue to explore the role of these receptors in this neurodegenerative disease. Indeed, all motor neurons affected in ALS are responsive to adenosine receptor ligands but interestingly, there are alterations in pre-symptomatic or early symptomatic stages that mirror those in advanced disease stages. Information starts to emerge pointing toward a beneficial role of A2A receptors (A2AR), most probably at early disease states, and a detrimental role of caffeine, in clear contrast with what occurs in other neurodegenerative diseases. However, some evidence also exists on a beneficial action of A2AR antagonists. It may happen that there are time windows where A2AR prove beneficial and others where their blockade is required. Furthermore, the same changes may not occur simultaneously at the different synapses. In line with this, it is not fully understood if ALS is a dying back disease or if it propagates in a centrifugal way. It thus seems crucial to understand how motor neuron dysfunction occurs, how adenosine receptors are involved in those dysfunctions and whether the early changes in purinergic signaling are compensatory or triggers for the disease. Getting this information is crucial before starting the design of purinergic based strategies to halt or delay disease progression.This work was supported by LISBOA-01-0145-FEDER-007391, project co-funded by FEDER through POR Lisboa 2020 (Programa Operacional Regional de Lisboa) from PORTUGAL 2020 and Fundação para a Ciência e Tecnologia (FCT) and by a Twinning action (SynaNet) from the EU H2020 program (Project Number: 692340). NR is in receipt of an FCT fellowship (PD /BD/113463/2015) and is a fellow of the M2B-Ph.D. Program.info:eu-repo/semantics/publishedVersio

Neuromodulación fina por adenosina y neuroprotección

Adenosine fine tuning neuromodulation is a very subtle change, similar to what e.g., a pianist does, modulating a sound through insertion of another sound; so, modifying the characteristics of the previous sound. This is what adenosine does to modulate neurotransmitter actions. Adenosine neuromodulation is operated through high affinity inhibitory A1 and excitatory A2A receptors. These receptors have the particularity of interacting with receptors for other neurotransmitters and neuromodulators as well as with adenosine transport systems. This modulation is involved in neuroprotection namely via adenosine A1 receptors in neurotoxicity during hypoxia, reactive oxygen species insults either inhibiting NMDA receptors or as part of interleukin-6 neuroprotecive effects. On the other hand A2A receptors mainly trigger the action of several promoters of neuroprotection, e.g., BDNF and GDNF.Key Words: Adenosine receptors, Neuromodulation, Neuroprotection.La neuromodulación fina por adenosina supone un cambio muy sutil, similar al que por ejemplo realiza un pianista, modulando un sonido a través de la inserción de otro, modificando así las características del sonido previo. Esto es lo que hace la adenosina para modular las acciones de los neurotransmisores. La neuromodulación por adenosina se realiza a través de receptores de alta afinidad inhibitorios A1 y excitatorios A2. Estos receptores poseen la particularidad de interaccionar con receptores para otros neurotransmisores y neuromodulares así como con los sistemas de transporte de adenosina. Esta modulación está implicada en la neuroprotección vía receptores de adenosina A1 en la neurotoxicidad producida durante la hipoxia, daños producidos por las especies reactivas del oxígeno inhibiendo los receptores NMDA o como parte de los efectos neuroprotectores de la interleukina-6. Por otro lado, los receptores A2A principalmente desencadenan la acción de varios promotores de la neuroprotección, como el BDNF y el GDNF.Palabras clave: Receptores de adenosina, Neuromodulación, Neuroprotección

Blockade of adenosine A2A receptors prevents protein phosphorylation in the striatum induced by cortical stimulation

©2006 Society for NeurosciencePrevious studies have shown that cortical stimulation selectively activates extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation and immediate early gene expression in striatal GABAergic enkephalinergic neurons. In the present study, we demonstrate that blockade of adenosine A2A receptors with caffeine or a selective A2A receptor antagonist counteracts the striatal activation of cAMP– protein kinase A cascade (phosphorylation of the Ser845 residue of the glutamate receptor 1 subunit of the AMPA receptor) and mitogenactivated protein kinase (ERK1/2 phosphorylation) induced by the in vivo stimulation of corticostriatal afferents. The results indicate that A2A receptors strongly modulate the efficacy of glutamatergic synapses on striatal enkephalinergic neurons.This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Drug Abuse, Department of Health and Human Services

Activation of adenosine A2A receptors induces TrkB translocation and increases BDNF-mediated phospho-TrkB localization in lipid rafts : implications for neuromodulation

Copyright © 2010 the authorsBrain-derived neurotrophic factor (BDNF) signaling is critical for neuronal development and transmission. Recruitment of TrkB receptors to lipid rafts has been hown to be necessary for the activation of specific signaling pathways and modulation of neurotransmitter release by BDNF. Since TrkB receptors are known to be modulated by adenosine A2A receptor activation, we hypothesized that activation of A2A receptors could influence TrkB receptor localization among different membrane microdomains. We found that adenosine A2A receptor agonists increased the levels of TrkB receptors in the lipid raft fraction of cortical membranes and potentiated BDNF-induced augmentation of phosphorylated TrkB levels in lipid rafts. Blockade of the clathrin-mediated endocytosis with monodansylcadaverine(100µM) did not modify the effects of theA2A receptor agonists but significantly impairedBDNFeffects on TrkB recruitment to lipid rafts. The effect of A2A receptor activation in TrkB localization was mimicked by 5 µM forskolin, an adenylyl cyclase activator. Also, it was blocked by the PKA inhibitors Rp-cAMPs and PKI-(14 –22), and by the Src-family kinase inhibitor PP2. Moreover, removal of endogenous adenosine or disruption of lipid rafts reduced BDNF stimulatory effects on glutamate release from cortical synaptosomes. Lipid raft integrity was also required for the effects of BDNF on hippocampal long-term potentiation at CA1 synapses. Our data demonstrate, for the first time, a BDNF-independent recruitment of TrkB receptors to lipid rafts induced by activation of adenosine A2A receptors, with functional consequences for TrkB phosphorylation and BDNF-induced modulation of neurotransmitter release and hippocampal plasticity.Supported by Fundacão para a Ciência e a Tecnologia (SFRH/BD/21374/2005 for N.A.L., SFRH/BD/21359/2005 for V.C.S., and SFRH/BPD/11528/2002 for D.B.P.) and by the European Union [European Cooperation in Science and Technology (COST) COST B30 concerted action, Neural Regeneration and Plasticity (NEREPLAS)]

Endogenous VIP VPAC1 receptor activation modulates hippocampal theta burst induced LTP: transduction pathways and GABAergic mechanisms

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Vasoactive intestinal peptide (VIP), acting on both VPAC1 and VPAC2 receptors, is a key modulator of hippocampal synaptic transmission, pyramidal cell excitability and long-term depression (LTD), exerting its effects partly through modulation GABAergic disinhibitory circuits. Yet, the role of endogenous VIP and its receptors in modulation of hippocampal LTP and the involvement of disinhibition in this modulation have scarcely been investigated. We studied the modulation of CA1 LTP induced by TBS via endogenous VIP release in hippocampal slices from young-adult Wistar rats using selective VPAC1 and VPAC2 receptor antagonists, evaluating its consequence for the phosphorylation of CamKII, GluA1 AMPA receptor subunits and Kv4.2 potassium channels in total hippocampal membranes obtained from TBS stimulated slices. Endogenous VIP, acting on VPAC1 (but not VPAC2) receptors, inhibited CA1 hippocampal LTP induced by TBS in young adult Wistar rats and this effect was dependent on GABAergic transmission and relied on the integrity of NMDA and CaMKII-dependent LTP expression mechanisms but not on PKA and PKC activity. Furthermore, it regulated the autophosphorylation of CaMKII and the expression and Ser438 phosphorylation of Kv4.2 potassium channels responsible for the A-current while inhibiting phosphorylation of Kv4.2 on Thr607. Altogether, this suggests that endogenous VIP controls the expression of hippocampal CA1 LTP by regulating disinhibition through activation of VPAC1 receptors in interneurons. This may impact the autophosphorylation of CaMKII during LTP, as well as the expression and phosphorylation of Kv4.2 K+ channels at hippocampal pyramidal cell dendrites.This work was supported national and international funding managed by Fundação para a Ciência e a Tecnologia (FCT, IP), Portugal. Grants: FCT UIDB/04046/2020 and UIDP/04046/2020 to BioISI, PTDC/SAU-NEU/103639/2008; and FCT/POCTI (PTDC/SAU-PUB/28311/2017) EPIRaft grant to DCR. Fellowships: SFRH/BPD/81358/2011 to DCR and Researcher contract: Norma Transitória—DL57/2016/CP1479/CT0044 to DCR.info:eu-repo/semantics/publishedVersio

Mobile robot for autonomous golf balls picking

This paper describes a robot to collect golf balls in a driving range, operating as autonomous and/or remotely operated. It uses a set of sensors which gives the robot capacities of surrounding environment perception and digital image processing to search for the balls in places with higher concentrations of balls. This system avoids stopping the players for ball collection permitting a higher use rate of the field

Post-cracking behaviour of selfcompacting steel fibre reinforced concrete

Self-compacting concrete (SCC) can be defined as concrete that is able to flow in the interior of the formwork, passing through the reinforcement and filling it in a natural manner, being consolidated under the action of its own weight. Adding the benefits of SCC to those resulting from the addition of discrete fibres to cement based materials, a high performance material, designated by steel fibre reinforced self-compacting concrete (SFRSCC), is obtained. In the present work the strategy followed to design SFRSCC is described, as well as, the experimental research carried out to characterize its flexural and compression behaviour. A special effort is done to assess the post-cracking behaviour, carrying out three point notched beam tests. The equivalent and the residual flexural tensile strength parameters, proposed by RILEM TC 162-TDF to characterize the toughness of steel fibre reinforced concrete (SFRC), are determined. To evaluate the stress-crack opening diagram of the designed SFRSCC, an inverse analysis is performed fitting the obtained experimental force-deflection curves.FEDER. MCT. Fundação para a Ciência e a Tecnologia (FCT) - SFRH/BSAB/291/2002-POCTI. Fundo Social Europeu (FSE) - SFRH/BSAB/291/2002-POCTI. MBT. SECIL. Bekaert. Comital. “Central do Pego”. Civitest Lda