Andrea Cabrera-Pastor

Andrea Cabrera-Pastor
Hospital Clínico Universitario de Valencia

PhD

About

66
Publications
4,540
Reads
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Citations
Introduction
I am interested in knowing how the brain works. The main objectives are (*) to identify the molecular mechanisms leading to cognitive and motor alterations in minimal hepatic encephalopathy and new therapeutic treatments to restore them, (*) to understand how the neuroinflammation alters the neurotransmission, (*) to characterize the role of cyclic GMP (especially extracellular cGMP) in the modulation of neurotransmission and learning and memory processes and (*) to identify the role of EVs.
Additional affiliations
April 2021 - present
Hospital Clínico Universitario de Valencia
Position
  • Researcher
September 2019 - November 2019
Mario Negri Institute for Pharmacological Research
Position
  • PostDoc Position
January 2018 - April 2021
Education
October 2009 - July 2014
January 2007 - September 2009
Fundación Hospital General Universitario de Valencia
Fundación Hospital General Universitario de Valencia
Field of study
  • Oncology
September 2005 - September 2006
University of Valencia and Association of Biologists
Field of study
  • Master in Clinical Analysis

Publications

Publications (66)
Article
Full-text available
It has been proposed that extracellular cGMP modulates the ability to learn a Y maze task, but the underlying mechanisms remained unknown. Here we show that extracellular cGMP, at physiological concentrations, modulates learning in the Y maze in a biphasic way by modulating the glutamate-nitric oxide-cGMP pathway in cerebellum. Extracellular cGMP r...
Article
Patients with hepatic encephalopathy (HE) show working memory and visuo-spatial orientation deficits. Hyperammonemia is a main contributor to cognitive impairment in HE. Hyperammonemic rats show impaired spatial learning and learning ability in the Y maze. Intracerebral administration of extracellular cGMP restores learning in the Y-maze. The under...
Article
Extracellular protein kinases, including cAMP-dependent protein kinase (PKA) modulate neuronal functions including NMDA receptor-dependent long-term potentiation. NMDA receptors activation increases calcium, which binds to calmodulin and activates nitric oxide synthase (NOS), increasing nitric oxide (NO) which activates guanylate cyclase, increasin...
Article
The glutamate-nitric oxide (NO)-cGMP pathway modulates some forms of learning. How glycine modulates this pathway is unclear. Glycine could modulate the pathway biphasically, enhancing its function through NMDA receptor activation or reducing it through glycine receptor activation. Chronic hyperammonemia impairs the glutamate-NO-cGMP pathway in the...
Article
The roles of high- and low-affinity AMPA receptors in modulating extracellular glutamate in cerebellum remain unclear. Altered glutamatergic neurotransmission is involved in neurological alterations in hyperammonemia, which affects differently high- and low-affinity AMPA receptors. The aims were to assess by in vivo microdialysis: a) the effects of...
Article
Full-text available
Chronic hyperammonemia alters membrane expression of AMPA and NMDA receptors subunits in hippocampus leading to impaired memory and learning. Increasing extracellular cGMP normalizes these alterations. However, it has not been studied whether hyperammonemia alters the function of AMPA and NMDA receptors. The aims of this work were: (1) assess if hy...
Article
Cyclic Guanosine-Monophosphate (cGMP) is implicated as second messenger in a plethora of pathways and its effects are executed mainly by cGMP-dependent protein kinases (PKG). It is involved in both peripheral (cardiovascular regulation, intestinal secretion, phototransduction, etc.) and brain (hippocampal synaptic plasticity, neuroinflammation, cog...
Article
Full-text available
Cirrhotic patients may experience alterations in the peripheral nervous system and in somatosensory perception. Impairment of the somatosensory system could contribute to cognitive and motor alterations characteristic of minimal hepatic encephalopathy (MHE), which affects up to 40% of cirrhotic patients. We assessed the relationship between MHE and...
Article
Full-text available
Background: Chronic hyperammonemia induces neuroinflammation in cerebellum, with glial activation and enhanced activation of the TNFR1-NF-kB-glutaminase-glutamate-GABA pathway. Hyperammonemia also increases glycinergic neurotransmission. These alterations contribute to cognitive and motor impairment. Activation of glycine receptors is reduced by e...
Article
Full-text available
Minimal hepatic encephalopathy is associated with changes in the peripheral immune system which are transferred to the brain, leading to neuroinflammation and thus to cognitive and motor impairment. Mechanisms by which changes in the immune system induce cerebral alterations remain unclear. Extracellular vesicles (EVs) seem to play a role in this p...
Article
Full-text available
Patients with Benign prostatic hyperplasia, low urinary tract symptoms, and erectile dysfunction (BPH/LUTS-ED) present chronic inflammation. We studied in patients with BPH/LUTS-ED the effect of tadalafil treatment (5 mg/day) on changes in peripheral inflammation, cognitive function, and the auditory evoked potential, “mismatch negativity” (MMN). N...
Article
Full-text available
Background: Minimal hepatic encephalopathy (MHE) in cirrhotic patients is associated with specific changes in parameters of the immune system reflecting a more pro-inflammatory environment than in patients without MHE. The aims of this work were to assess the effects of rifaximin treatment of cirrhotic patients with MHE on: (1) MHE; (2) intermedia...
Article
Activated microglia and increased brain IL-1β play a main role in cognitive impairment in much pathology. We studied the role of IL-1β in neuroinflammation-induced impairment of the following different types of learning and memory: novel object recognition (NOR), novel object location (NOL), spatial learning, reference memory (RM), and working memo...
Article
Full-text available
Chronic hyperammonemia impairs spatial memory by altering membrane expression of GluA1 and GluA2 subunits of AMPA receptors in hippocampus. Intracerebral administration of extracellular cGMP to hyperammonemic rats restores spatial memory and membrane expression of AMPA receptors. The underlying molecular mechanisms remain unknown and cannot be anal...
Article
Several million patients with liver cirrhosis suffer minimal hepatic encephalopathy (MHE), with mild cognitive and coordination impairments that reduce their quality of life and life span. Hyperammonemia and peripheral inflammation act synergistically to induce these neurological alterations. We propose that MHE appearance is due to changes in peri...
Article
Full-text available
Background & Aims Chronic hyperammonemia induces neuroinflammation which mediates cognitive impairment. How hyperammonemia induces neuroinflammation remains unclear. We propose the hypothesis that chronic hyperammonemia would induce peripheral inflammation that would induce neuroinflammation and cognitive impairment, which would be prevented by red...
Article
Trafficking of glutamate, glutamine and GABA between astrocytes and neurons is essential to maintain proper neurotransmission. Chronic hyperammonemia alters neurotransmission and cognitive function. The aims of this work were to analyze in cerebellum of rats the effects of chronic hyperammonemia on: a) extracellular glutamate, glutamine and GABA co...
Article
Full-text available
Background: Hyperammonemic rats reproduce the cognitive alterations of patients with hepatic encephalopathy, including altered spatial memory, attributed to altered membrane expression of AMPA receptor subunits in hippocampus. Neuroinflammation mediates these cognitive alterations. We hypothesized that hyperammonemia-induced increase in IL-1β in h...
Article
Full-text available
It has been proposed that developmental exposure to pesticides contributes to increasing prevalence of neurodevelopmental disorders in children, such as attention deficit with hyperactivity (ADHD) and to alterations in coordination skills. However, the mechanisms involved in these alterations remain unclear. We analyzed the effects on spontaneous m...
Article
Full-text available
There is increasing evidence that extracellular cGMP modulates glutamatergic neurotransmission and some forms of learning. However, the underlying mechanisms remain unknown. We proposed the hypotheses that extracellular cGMP may regulate membrane expression of AMPA receptors. To do this extracellular cGMP should act on a membrane protein and activa...
Article
Hyperammonemia is a main contributor to cognitive impairment and motor in-coordination in patients with hepatic encephalopathy. Hyperammonemia-induced neuroinflammation mediates the neurological alterations in hepatic encephalopathy. Intracerebral administration of extracellular cGMP restores some but not all types of cognitive impairment. Motor in...
Article
Exposure to pesticides has been associated with neurodevelopmental toxicity. Usually people are exposed to mixtures of pesticides. However, most studies analyze the effects of individual pesticides. Developmental exposure to mixtures of pesticides may result in additive effects or in antagonistic or synergistic effects. The aim of this work was to...
Article
Hyperammonemia contributes to altered neurotransmission and cognition in patients with hepatic encephalopathy. Hyperammonemia in rats affects differently high- and low-affinity AMPA receptors (AMPARs) in cerebellum. We hypothesized that hyperammonemia would alter differently membrane expression of AMPARs GluA1 and GluA2 subunits by altering its pho...
Article
Full-text available
Pruritus is a common symptom in chronic liver diseases, which may also alter thermal sensitivity. The underlying mechanisms remain unclear and treatments are not satisfactory. Portal-systemic shunting has been proposed to alter thermal sensitivity in cirrhotics. Inflammation-induced enhanced activity of the Transient Receptor Potential Vanilloid 1...
Article
Aims: Patients with liver disease may develop hepatic encephalopathy (HE), with cognitive impairment and motor in-coordination. Rats with HE due to portacaval shunts (PCS) show motor in-coordination. We hypothesized that in PCS rats: (i) Motor in-coordination would be due to enhanced GABAergic tone in cerebellum; (ii) increased GABAergic tone woul...
Article
Full-text available
Inflammation contributes to cognitive impairment in patients with hepatic encephalopathy (HE). However, the process by which peripheral inflammation results in cognitive impairment remains unclear. In animal models, neuroinflammation and altered neurotransmission mediate cognitive impairment. Taking into account these data, we hypothesized that in...
Article
The use of pesticides has been associated with impaired neurodevelopment in children. The aims of this work were to assess: 1) the effects on spatial learning of developmental exposure to pesticides 2) if the effects are sex-dependent and 3) if hippocampal neuroinflammation is associated with the impairment of spatial learning. We analyzed the effe...
Article
Full-text available
Background Peripheral inflammation contributes to the neurological alterations in hepatic encephalopathy (HE). Neuroinflammation and altered GABAergic neurotransmission mediate cognitive and motor alterations in rats with HE. It remains unclear (a) if neuroinflammation and neurological impairment in HE are a consequence of peripheral inflammation a...
Article
Full-text available
Background Hyperammonemia induces neuroinflammation and increases GABAergic tone in the cerebellum which contributes to cognitive and motor impairment in hepatic encephalopathy (HE). The link between neuroinflammation and GABAergic tone remains unknown. New treatments reducing neuroinflammation and GABAergic tone could improve neurological impairme...
Article
Full-text available
Background Patients with liver cirrhosis and minimal hepatic encephalopathy (MHE) show mild cognitive impairment and spatial learning dysfunction. Hyperammonemia acts synergistically with inflammation to induce cognitive impairment in MHE. Hyperammonemia-induced neuroinflammation in hippocampus could contribute to spatial learning impairment in MHE...
Article
Full-text available
There are no specific treatments for the neurological alterations of cirrhotic patients with minimal hepatic encephalopathy (MHE). Rats with MHE due to portacaval shunt (PCS) show impaired spatial learning. The underlying mechanisms remain unknown. The aims of this work were to assess: (a) whether PCS rats show neuroinflammation in hippocampus, (b)...
Article
Hepatic encephalopathy (HE) is a complex neuropsychiatric syndrome affecting patients with liver diseases, mainly those with liver cirrhosis. The mildest form of HE is minimal HE (MHE), with mild cognitive impairment, attention deficit, psychomotor slowing and impaired visuo-motor and bimanual coordination. MHE may progress to clinical HE with wors...
Article
Chronic liver disease (e.g. cirrhosis) affects brain function. There is a high incidence of mild cognitive impairment and psychomotor slowing in patients with cirrhosis. This condition, known as minimal hepatic encephalopathy (MHE) affects more than 2 million people in the European Union and has serious health, social and economic consequences. The...
Article
Full-text available
Chronic liver disease (e.g. cirrhosis) affects brain function. There is a high incidence of mild cognitive impairment and psychomotor slowing in patients with cirrhosis. This condition, known as minimal hepatic encephalopathy (MHE) affects more than 2 million people in the European Union and has serious health, social and economic consequences. The...
Article
The cognitive and motor alterations in hepatic encephalopathy (HE) are the final result of altered neurotransmission and communication between neurons in neuronal networks and circuits. Different neurotransmitter systems cooperate to modulate cognitive and motor function, with a main role for glutamatergic and GABAergic neurotransmission in differe...
Article
Full-text available
Treatment of patients with acute liver failure (ALF) is unsatisfactory and mortality remains unacceptably high. Blocking NMDA receptors delays or prevents death of rats with ALF. The underlying mechanisms remain unclear. Clarifying these mechanisms will help to design more efficient treatments to increase patient's survival. The aim of this work wa...
Article
Patients with liver cirrhosis may present impaired sleep-wake and circadian rhythms, relative adrenal insufficiency and altered hypothalamus-pituitary-adrenal gland (HPA) axis. The underlying mechanisms remain unclear. Circadian rhythms are modulated by corticosteroids which secretion is regulated by HPA axis. Hyperammonemia alters circadian rhythm...
Article
This mini-review focus on our studies on alterations in glutamatergic neurotransmission and their role in neurological alterations in rat models of chronic hyperammonemia and hepatic encephalopathy (HE). Hyperammonemia impairs the glutamate-nitric oxide (NO)-cGMP pathway in cerebellum, which is responsible for reduced learning ability. We studied t...
Article
Previous studies show that chronic hyperammonemia impairs learning ability of rats by impairing the glutamate-nitric oxide (NO)-cyclic guanosine mono-phosphate (cGMP) pathway in cerebellum. Three types of glutamate receptors cooperate in modulating the NO-cGMP pathway: metabotropic glutamate receptor 5 (mGluR5), (RS)-α-amino-3-hydroxy-5-methyl-4-is...
Article
Background In advanced-stage (IIIB or IV) non-small-cell lung cancer (NSCLC), combination chemotherapy has demonstrated response rates of 20% and a 1-year survival rate of 30%. We conducted a multicentre, open-label, nonrandomised phase II trial to determine the efficacy and tolerability of sequential monotherapy with gemcitabine followed by paclit...
Article
Epidermal growth factor receptor (EGFR) is overexpressed in a variety of epithelial malignancies including lung cancer. A soluble fragment of the EGFR extracellular domain (sEGFR) can be detected in the blood of patients who have non-small-cell lung cancer (NSCLC), but its clinical/ prognostic role must be further elucidated. sEGFR concentration wa...
Article
Circulating DNA is observed at higher concentrations in patients with lung cancer than in controls. Qualitative and quantitative analysis of circulating DNA is a promising noninvasive tool. Our aim was to prospectively study the association between the catalytic subunit of telomerase (human telomerase reverse transcriptase [hTERT]) in plasma and cl...
Article
Metabotropic glutamate receptors (mGluRs) modulate important processes in cerebellum including long-term depression, which also requires formation of nitric oxide (NO) and cGMP. Some reports suggest that mGluRs could modulate the NO-cGMP pathway in cerebellum. However this modulation has not been studied in detail. The aim of this work was to asses...
Article
Qualitative analysis of circulating DNA in the blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the presence of KRAS mutations at codon 12 and several clinical variables in advanced non-small cell lung cancer (NSCLC) patients. We examined 308 stage IIIB and IV NSCLC patients who were tre...
Article
e17032 Background: In cancer, systematic analysis of mRNA expression levels can contribute to define a molecular network of lung carcinogenesis and establish predictive and prognostic molecular markers. Altered mRNA expression in certain angiogenic and anti-angiogenic genes such as vascular endothelial growth factor family of ligands and their rece...
Article
e22070 Background: HLA-G is a human non-classical MHC molecule, mainly expressed in the trophoblast whose main function is to suppress immunologic activity that allows maternal tolerance to phoetus. On the other hand, infiltrating regulatory T lymphocytes (Treg) could promote peripheral inmunotolerance fo oncogenic transformation. Methods: We perfo...
Article
e22108 Background: An increase in VEGF expression in tumour or some blood compartments (i.e. serum or plasma) has been found in solid tumours of various origins. Several studies have suggested that ligands and receptors of the VEGFs/VEGFR system play an important role in tumour growth and is associated with metastasis and poor prognosis. The aim of...
Article
e22207 Background: NSCLC is a major cause of cancer-related death worldwide. The prognosis for lung cancer patients is poor with 5-years survival rates being less than 15%. It is known that angiogenesis is an essential event for solid tumour growth. Vascular endothelial growth factor (VEGF) family of ligand and receptors (VEGFR) are described as po...
Article
Introduction: Non-small cell lung cancer (NSCLC) is the leading cause of cancer deaths in the world. Although early-stage non-small-cell lung cancer (NSCLC) is considered a potentially curable disease following complete resection, patients have a wide spectrum of survival according to stage. Within each stage, gene expression profiles can identify...
Article
It has been analyzed the frequency of p16 inactivation in 67 blood samples of patients diagnosed with advanced non-small cell lung cancer (NSCLC), to establish the relationship between p16 inactivation and time to progression (TTP) and overall survival (OS), and its relationship with various clinical parameters. This is a retrospective study of 67...