A5043580023- Neuroscience and Neuropharmacology Research
- Adenosine and Purinergic Signaling
- Pancreatic function and diabetes
- Receptor Mechanisms and Signaling
- Neurotransmitter Receptor Influence on Behavior
- Neuroinflammation and Neurodegeneration Mechanisms
- Parkinson's Disease Mechanisms and Treatments
- Vagus Nerve Stimulation Research
- Neurological disorders and treatments
- Nerve injury and regeneration
- Diabetes Treatment and Management
- Genetic Neurodegenerative Diseases
- Cardiac electrophysiology and arrhythmias
- Advanced Memory and Neural Computing
- Neurogenesis and neuroplasticity mechanisms
- Cardiac Ischemia and Reperfusion
- Ion channel regulation and function
- Neural dynamics and brain function
- Neurological Complications and Syndromes
- Diet, Metabolism, and Disease
- Regulation of Appetite and Obesity
- Ion Transport and Channel Regulation
- Neuroendocrine regulation and behavior
- Pharmacological Receptor Mechanisms and Effects
- Metabolism, Diabetes, and Cancer
University of Coimbra
2009-2023
Czech Academy of Sciences, Institute of Physiology
2019
University of Gothenburg
2017-2019
Centro de Neurociências e Biologia Celular
2009
Abstract Despite the characteristic etiologies and phenotypes, different brain disorders rely on common pathogenic events. Glutamate-induced neurotoxicity is a event shared by disorders. Another occurring in pathological conditions increase of extracellular ATP levels, which now recognized as danger harmful signal brain, heralded ability P2 receptors (P2Rs) to affect wide range Yet, how P2R contribute neurodegeneration remains poorly defined. For that purpose, we examined contribution P2Rs...
Abnormal accumulation of aggregated α-synuclein (aSyn) is a hallmark sporadic and familial Parkinson's disease (PD) related synucleinopathies. Recent studies suggest neuroprotective role adenosine A2A receptor (A2AR) antagonists in PD. Nevertheless, the precise molecular mechanisms underlying this neuroprotection remain unclear. We assessed impact A2AR blockade or genetic deletion (A2AR KO) on synaptic plasticity neuronal cell death induced by aSyn oligomers. found that impairment LTP...
Abstract Neurodegeneration is a process transversal to neuropsychiatric diseases and the understanding of its mechanisms should allow devising strategies prevent this irreversible step in brain diseases. caused by seizures critical aggravation temporal lobe epilepsy, but remain undetermined. Convulsions trigger an elevation extracellular adenosine upregulate A 2A receptors (A R), which have been associated with control neurodegenerative Using rat mouse kainate model we now tested whether R...
Increased ATP release and its extracellular catabolism through CD73 (ecto-5′-nucleotidase) lead to the overactivation of adenosine A2A receptors (A2AR), which occurs in different brain disorders. A2AR blockade blunts mood memory dysfunction caused by repeated stress, but it is unknown if increased coupled CD73-mediated formation responsible for upon stress. This was now investigated adult rats subject stress 14 consecutive days. Frontocortical hippocampal synaptosomes from stressed displayed...
Adenosine A2A receptors (A2AR) are activated upon increased synaptic activity to assist in the implementation of long-term plastic changes at synapses. While involvement A2AR control prefrontal cortex (PFC)-dependent behavior such as working memory, reversal learning and effort-based decision making has been reported, it is not known whether glutamatergic synapse plasticity within medial PFC (mPFC). To elucidate that, we tested blockade affects (LTP) excitatory postsynaptic potentials (EPSP)...
Abstract Extracellular ATP can be a danger signal, but its role in striatal circuits afflicted Parkinson’s disease (PD) is unclear and was now investigated. particularly released at high stimulation intensities from purified nerve terminals of mice, which were endowed with different ATP-P2 receptors (P2R), although P2R antagonists did not alter corticostriatal transmission or plasticity. Instead, extracellularly catabolized into adenosine through CD73 to activate A 2A (A R) modulating...
Extracellular ATP is a danger signal to the brain and contributes neurodegeneration in animal models of Alzheimer's disease through its extracellular catabolism by CD73 generate adenosine, bolstering activation adenosine A 2A receptors (A R).Convulsive activity leads increased release, with resulting morphological alterations being eliminated R blockade.However, it not known if upon convulsions there CD73-mediated coupling between release overactivation, causing neurodegeneration.We now show...
Characterising the molecular networks that negatively regulate pancreatic β-cell function is essential for understanding underlying pathogenesis and developing new treatment strategies type 2 diabetes. We recently identified serine/threonine protein kinase 25 (STK25) as a critical regulator of ectopic fat storage, meta-inflammation, fibrosis in liver skeletal muscle. Here, we assessed role STK25 control progression non-alcoholic fatty pancreas disease context chronic exposure to dietary...
Abstract Prefrontal cortex ( PFC ) circuits are modulated by dopamine acting on D 1 ‐ and 2 ‐like receptors, which pharmacologically exploited to manage neuropsychiatric conditions. Adenosine A 2A receptors (A R also control ‐related responses antagonists potential anti‐psychotic drugs. As tight antagonistic –D synergistic interactions occur in other brain regions, we now investigated the crosstalk between /D controlling synaptic transmission layers II / III V mouse coronal slices. Dopamine...
Adenosine A2A receptors (A2AR) were recently described to control synaptic plasticity and network activity in the prefrontal cortex (PFC). We now probed role of these PFC A2AR by evaluating behavioral performance (locomotor activity, anxiety-related behavior, cost-benefit decision making working memory) rats upon viral shA2AR-mediated downregulation selectively prelimbic medial (PLmPFC). The most evident alteration observed shA2AR-treated rats, when compared sh-control-treated was a decrease...
Summary The incretin hormone glucagon-like peptide 1(7-36) (GLP-1(7-36)) stimulates insulin and inhibits glucagon secretion. mechanisms by which GLP-1 suppresses release are unclear as glucagon-secreting α-cells express receptors (GLP-1Rs) at very low levels. Here, we examine the underlying mechanisms. We find that both GLP-1(7-36) its degradation product GLP-1(9-36) inhibit secretion physiological (pM) concentrations. Whereas effect of is sensitive to PKA inhibition, exerts a...
KATP ion channels play a key role in glucose-stimulated insulin secretion. However, many drugs block as "off targets" leading to hyperinsulinaemia and hypoglycaemia. As such are often lipophilic, the aim was examine relationship between drug lipophilicity (P) IC 50 for explore if 50's of statins could be predicted from their whether this would allow one forecast acute action on secretion.A meta-analysis 26 nonsulphonylurea, blockers performed. From this, pravastatin simvastatin were then...
Decreased plasma adiponectin has been implicated as a cause of diabetes. However, the functional impact on glucose-dependent responses β-cells remains poorly understood. Here we have investigated whether chronically and acutely increased levels affect electrical activity (sharp electrodes) insulin secretion in using respectively, overexpressing (APNtg) mice acute application adiponectin. In exposure experiments, (20 µg/ml, 11 mM glucose) 42% β-cell (measured fraction ‘active phase’) 32%....