Adenosine A Receptor Blockade Provides More Effective Benefits at the Onset Rather than after Overt Neurodegeneration in a Rat Model of Parkinson's Disease.

Adenosine A receptor (AR) antagonists are the leading nondopaminergic therapy to manage Parkinson's disease (PD) since they afford both motor benefits and neuroprotection. PD begins with a synaptic dysfunction and damage in the striatum evolving to an overt neuronal damage of dopaminergic neurons in the substantia nigra. We tested if AR antagonists are equally effective in controlling these two degenerative processes.

Modification of astrocytic Cx43 hemichannel activity in animal models of AD: modulation by adenosine A receptors.

Increasing evidence implicates astrocytic dysfunction in Alzheimer's disease (AD), a neurodegenerative disorder characterised by progressive cognitive loss. The accumulation of amyloid-β (Aβ) plaques is a histopathological hallmark of AD and associated with increased astrocyte reactivity. In APP/PS1 mice modelling established AD (9 months), we now show an altered astrocytic morphology and enhanced activity of astrocytic hemichannels, mainly composed by connexin 43 (Cx43).

Astrocytic A receptors silencing negatively impacts hippocampal synaptic plasticity and memory of adult mice.

Astrocytes are wired to bidirectionally communicate with neurons namely with synapses, thus shaping synaptic plasticity, which in the hippocampus is considered to underlie learning and memory. Adenosine A receptors (A R) are a potential candidate to modulate this bidirectional communication, since A R regulate synaptic plasticity and memory and also control key astrocytic functions. Nonetheless, little is known about the role of astrocytic A R in synaptic plasticity and hippocampal-dependent memory.

Downregulation of Sirtuin 1 Does Not Account for the Impaired Long-Term Potentiation in the Prefrontal Cortex of Female APPswe/PS1dE9 Mice Modelling Alzheimer's Disease.

Alzheimer's disease (AD), which predominantly affects women, involves at its onset a metabolic deregulation associated with a synaptic failure. Here, we performed a behavioral, neurophysiological and neurochemical characterization of 9-month-old female APPswe/PS1dE9 (APP/PS1) mice as a model of early AD. These animals showed learning and memory deficits in the Morris water maze, increased thigmotaxis and anxiety-like behavior and showed signs of fear generalization.

What If…? Pandemic policy-decision-support to guide a cost-benefit-optimised, country-specific response.

Background: After 18 months of responding to the COVID-19 pandemic, there is still no agreement on the optimal combination of mitigation strategies. The efficacy and collateral damage of pandemic policies are dependent on constantly evolving viral epidemiology as well as the volatile distribution of socioeconomic and cultural factors. This study proposes a data-driven approach to quantify the efficacy of the type, duration, and stringency of COVID-19 mitigation policies in terms of transmission control and economic loss, personalised to individual countries.

CD73-Mediated Formation of Extracellular Adenosine Is Responsible for Adenosine A Receptor-Mediated Control of Fear Memory and Amygdala Plasticity.

Adenosine A receptors (AR) control fear memory and the underlying processes of synaptic plasticity in the amygdala. In other brain regions, AR activation is ensured by ATP-derived extracellular adenosine formed by ecto-5'-nucleotidase or CD73. We now tested whether CD73 is also responsible to provide for the activation of AR in controlling fear memory and amygdala long-term potentiation (LTP).

Adenosine A receptors blockade attenuates dexamethasone-induced alterations in cultured astrocytes.

Anxiety involves abnormal glucocorticoid signalling and altered glia-neuron communication in brain regions processing emotional responses. Adenosine A receptor (AR) blockade ameliorates mood and memory impairments by preventing synaptic dysfunction and astrogliosis. Since the glucocorticoid dexamethasone (DEX) can mimic early life-stress conditions, leading to anxiety-like behaviours, we now tested if AR blockade prevents alterations in the morphology and function of astrocytes exposed to DEX.

Challenges of Large-Scale Multi-Camera Datasets for Driver Monitoring Systems.

Tremendous advances in advanced driver assistance systems (ADAS) have been possible thanks to the emergence of deep neural networks (DNN) and Big Data (BD) technologies. Huge volumes of data can be managed and consumed as training material to create DNN models which feed functions such as lane keeping systems (LKS), automated emergency braking (AEB), lane change assistance (LCA), etc. In the ADAS/AD domain, these advances are only possible thanks to the creation and publication of large and complex datasets, which can be used by the scientific community to benchmark and leverage research and development activities.

Impact of blunting astrocyte activity on hippocampal synaptic plasticity in a mouse model of early Alzheimer's disease based on amyloid-β peptide exposure.

Amyloid-β peptides (Aβ) accumulate in the brain since early Alzheimer's disease (AD) and dysregulate hippocampal synaptic plasticity, the neurophysiological basis of memory. Although the relationship between long-term potentiation (LTP) and memory processes is well established, there is also evidence that long-term depression (LTD) may be crucial for learning and memory. Alterations in synaptic plasticity, namely in LTP, can be due to communication failures between astrocytes and neurons; however, little is known about astrocytes' ability to control hippocampal LTD, particularly in AD-like conditions.

Association Between Adenosine A Receptors and Connexin 43 Regulates Hemichannels Activity and ATP Release in Astrocytes Exposed to Amyloid-β Peptides.

Increasing evidence implicates astrocytes and the associated purinergic modulation in Alzheimer's disease (AD), characterized by cognitive deficits involving the extracellular amyloid-β peptides (Aβ) accumulation. Aβ can affect astrocytic gliotransmitters release, namely ATP, which is rapidly metabolized into adenosine by ecto-5'-nucleotidase, CD73, resulting in adenosine A receptors (AR) activation that bolsters neurodegeneration. AD's brains exhibit an upregulation of AR and of connexin 43 (Cx43), which in astrocytes forms hemichannels that can mediate ATP release.

Increased ATP release and CD73-mediated adenosine A receptor activation mediate convulsion-associated neuronal damage and hippocampal dysfunction.

Extracellular ATP is a danger signal to the brain and contributes to neurodegeneration in animal models of Alzheimer's disease through its extracellular catabolism by CD73 to generate adenosine, bolstering the activation of adenosine A receptors (AR). Convulsive activity leads to increased ATP release, with the resulting morphological alterations being eliminated by AR blockade. However, it is not known if upon convulsions there is a CD73-mediated coupling between ATP release and AR overactivation, causing neurodegeneration.

Deletion of CD73 increases exercise power in mice.

Ecto-5'-nucleotidase or CD73 is the main source of extracellular adenosine involved in the activation of adenosine A receptors, responsible for the ergogenic effects of caffeine. We now investigated the role of CD73 in exercise by comparing female wild-type (WT) and CD73 knockout (KO) mice in a treadmill-graded test to evaluate running power, oxygen uptake (V̇O), and respiratory exchange ratio (RER) - the gold standards characterizing physical performance. Spontaneous locomotion in the open field and submaximal running power and V̇O in the treadmill were similar between CD73-KO and WT mice; V̇Omax also demonstrated equivalent aerobic power, but CD73-KO mice displayed a 43.

l-α-aminoadipate causes astrocyte pathology with negative impact on mouse hippocampal synaptic plasticity and memory.

Increasing evidence shows that astrocytes, by releasing and uptaking neuroactive molecules, regulate synaptic plasticity, considered the neurophysiological basis of memory. This study investigated the impact of l-α-aminoadipate (l-AA) on astrocytes which sense and respond to stimuli at the synaptic level and modulate hippocampal long-term potentiation (LTP) and memory. l-AA selectivity toward astrocytes was proposed in the early 70's and further tested in different systems.

Motor Deficits Coupled to Cerebellar and Striatal Alterations in Ube3a Mice Modelling Angelman Syndrome Are Attenuated by Adenosine A Receptor Blockade.

Angelman syndrome (AS) is a neurogenetic disorder involving ataxia and motor dysfunction, resulting from the absence of the maternally inherited functional Ube3a protein in neurons. Since adenosine A receptor (AR) blockade relieves synaptic and motor impairments in Parkinson's or Machado-Joseph's diseases, we now tested if AR blockade was also effective in attenuating motor deficits in an AS (Ube3a) mouse model and if this involved correction of synaptic alterations in striatum and cerebellum. Chronic administration of the AR antagonist SCH58261 (0.

Use of knockout mice to explore CNS effects of adenosine.

The initial exploration using pharmacological tools of the role of adenosine receptors in the brain, concluded that adenosine released as such acted on AR to inhibit excitability and glutamate release from principal neurons throughout the brain and that adenosine A receptors (AR) were striatal-'specific' receptors controlling dopamine DR. This indicted AR as potential controllers of neurodegeneration and AR of psychiatric conditions. Global knockout of these two receptors questioned the key role of AR and instead identified extra-striatal AR as robust controllers of neurodegeneration.

Purinergic signaling orchestrating neuron-glia communication.

This review discusses the evidence supporting a role for ATP signaling (operated by PX and PY receptors) and adenosine signaling (mainly operated by A and A receptors) in the crosstalk between neurons, astrocytes, microglia and oligodendrocytes. An initial emphasis will be given to the cooperation between adenosine receptors to sharpen information salience encoding across synapses. The interplay between ATP and adenosine signaling in the communication between astrocytes and neurons will then be presented in context of the integrative properties of the astrocytic syncytium, allowing to implement heterosynaptic depression processes in neuronal networks.

Adenosine A receptors format long-term depression and memory strategies in a mouse model of Angelman syndrome.

Angelman syndrome (AS) is a neurodevelopmental disorder caused by loss of function of the maternally inherited Ube3a neuronal protein, whose main features comprise severe intellectual disabilities and motor impairments. Previous studies with the Ube3a mouse model of AS revealed deficits in synaptic plasticity and memory. Since adenosine A receptors (AR) are powerful modulators of aberrant synaptic plasticity and AR blockade prevents memory dysfunction in various brain diseases, we tested if AR could control deficits of memory and hippocampal synaptic plasticity in AS.

Neuronal adenosine A receptors signal ergogenic effects of caffeine.

Caffeine is one of the most used ergogenic aid for physical exercise and sports. However, its mechanism of action is still controversial. The adenosinergic hypothesis is promising due to the pharmacology of caffeine, a nonselective antagonist of adenosine A and A receptors.

Protocol For A Perioperative Approach To Patients With Coronary Stents Undergoing Non Cardiac Surgery.

Patients undergoing angioplasty and stent insertion require double prophylactic anti-aggregation or monotherapy. This is a challenging procedure with a high risk of morbidity and coronary mortality. The aim of this protocol is to provide guidelines for a presurgical approach to patients with a coronary stent who will be undergoing non-coronary surgery.