A5017953059- Tryptophan and brain disorders
- Neuroscience and Neuropharmacology Research
- Sirtuins and Resveratrol in Medicine
- Neurotransmitter Receptor Influence on Behavior
- Forensic Toxicology and Drug Analysis
- Alzheimer's disease research and treatments
- Biochemical effects in animals
- Neuroinflammation and Neurodegeneration Mechanisms
- Phosphodiesterase function and regulation
- Psychedelics and Drug Studies
- Cannabis and Cannabinoid Research
- Calcium signaling and nucleotide metabolism
- S100 Proteins and Annexins
- Stress Responses and Cortisol
- Nerve injury and regeneration
- Epilepsy research and treatment
- Cholinesterase and Neurodegenerative Diseases
- Pancreatic function and diabetes
- Adipose Tissue and Metabolism
- Histone Deacetylase Inhibitors Research
- Genetic Neurodegenerative Diseases
- Parkinson's Disease Mechanisms and Treatments
- Adenosine and Purinergic Signaling
- Diet and metabolism studies
- Metabolism, Diabetes, and Cancer
Universidad de Navarra
2016-2025
Navarre Institute of Health Research
2015-2024
Christie's
2023
Creative Commons
2023
Karolinska Institutet
2012-2021
Hospital de Galdakao
2019
Sanofi (France)
2019
Complejo Hospitalario Universitario de Granada
2017
Hospital Universitario Virgen de las Nieves
2013
Zero to Three
2011
Inhibitors of phosphodiesterase 5 (PDE5) affect signalling pathways by elevating cGMP, which is a second messenger involved in processes neuroplasticity. In the present study, effects PDE5 inhibitor, sildenafil, on pathological features Alzheimer's disease and memory-related behaviour were investigated.Sildenafil was administered to Tg2576 transgenic mouse model age-matched negative littermates (controls). Memory function analysed using Morris water maze test fear conditioning tasks....
Abstract Dravet Syndrome (DS) is an encephalopathy with epilepsy associated multiple neuropsychiatric comorbidities. In up to 90% of cases, it caused by functional happloinsufficiency the SCN1A gene, which encodes alpha subunit a voltage-dependent sodium channel (Nav1.1). Preclinical development new targeted therapies requires accessible animal models recapitulate disease at genetic and clinical levels. Here we describe that C57BL/6 J knock-in mouse strain carrying heterozygous, clinically...
Summary Several studies support the relation between leptin and Alzheimer's disease ( AD ). We show that levels in CSF are unchanged as subjects progress to . However, hippocampus, signalling was decreased localization shifted, being more abundant reactive astrocytes less neurons. Similar translocation of found brains from Tg2576 apoE4 mice. Moreover, an enhancement receptors hippocampus young mice primary neurons treated with Aβ 1‐42 In contrast, old showed levels. findings those seen were...
We previously described a heterozygous mouse model overexpressing human HA-tagged 24S-hydroxylase (CYP46A1) utilizing ubiquitous expression vector. In this study, we generated homozygotes of these mice with circulating levels 24OH 30-60% higher than the heterozygotes. Female homozygous CYP46A1 transgenic mice, aged 15 months, showed an improvement in spatial memory Morris water maze test as compared to wild type mice. The N-Methyl-D-Aspartate receptor 1, phosphorylated-N-Methyl-D-Aspartate...
Inflammation plays an important role in Alzheimer's disease (AD) and other neurodegenerative disorders. Although chronic inflammation later stages of AD is well described, little known about the inflammatory processes preclinical or early prior to plaque deposition. In this study, we report that mediator S100A8 increased with aging mouse brain. It observed as extracellular aggregates, which do not correspond corpora amylacea. aggregation enhanced hippocampi two different models for amyloid-β...
Dravet syndrome is a genetic encephalopathy characterized by severe epilepsy combined with motor, cognitive, and behavioral abnormalities. Current antiepileptic drugs achieve only partial control of seizures provide little benefit on the patient's neurological development. In >80% cases, disease caused haploinsufficiency SCN1A gene, which encodes alpha subunit Nav1.1 voltage-gated sodium channel. Novel therapies aim to restore expression in order address all manifestations. We evidence that...
It has been established that ageing is the major risk factor for cognitive deficiency and it becoming increasingly evident insulin resistance another factor. Biological plausibility a link between dementia relevant understanding disease etiology, to form bases prevention efforts decrease burden. In present study, peripheral central was found in SAMP8 mice (aging mouse model) accompanied by deficiencies. Furthermore, marked inflammatory state observed mice, followed neuroinflammation could be...
Sirtuin 2 (SIRT2), a NAD+-dependent deacetylase, has been implicated in aging and neurodegenerative diseases such as Alzheimer's disease (AD). While global SIRT2 inhibition shown promise reducing amyloid-beta pathology cognitive deficits different mouse models of AD, peripheral associated with adverse effects, increased inflammation. This suggests that targeted specific cellular populations within the brain may represent more precise effective approach for treatment AD. To explore this...
3,4-methylenedioxymethamphetamine (MDMA) causes a persistent loss of dopaminergic cell bodies in the substantia nigra mice. Current evidence indicates that such neurotoxicity is due to oxidative stress but source free radicals remains unknown. Inhibition mitochondrial electron transport chain complexes by MDMA was assessed as possible source.Activities after were evaluated spectrophotometrically. In situ visualization superoxide production striatum ethidium fluorescence and striatal dopamine...
The presence of the E4 allele apolipoprotein E (apoE) is strongest known genetic risk factor for sporadic Alzheimer's disease (AD). Other factors developing AD have been identified, including lifestyle such as dietary habits. present study was designed to explore impact interaction between variant human apoE isoforms and a high carbohydrate diet (HCD) on mechanisms behind learning memory retention. As an investigative model, we compared young apoE3 apoE4 target replacement mice fed HCD 6...
The senescence-accelerated mouse-prone 8 (SAMP8), used as a model of aging, displays many established pathological features Alzheimer's disease. Cognitive impairments and increased levels hyperphosphorylated tau are found in the hippocampus SAMP8 mice along with an β-secretase activity amyloid-β (Aβ) depositions that increase number extent age. Based on previous study from our laboratory showing amelioration cognitive pathology by sildenafil, this we tested whether drug could also modulate...
Alterations in cholesterol metabolism the brain have a major role physiology of Alzheimer's disease (AD). Oxysterols are metabolites with multiple implications memory functions and neurodegeneration. Previous studies shown detrimental effects neurons, but its effect glial cells is unknown. We used high-fat/high-cholesterol diet mice to study hypercholesterolemia over alarmin S100A8 cascade hippocampus. Using CYP27Tg, transgenic mouse model, we show that influence on mediated by excess...
Abstract Alzheimer's disease (AD) is the most common form of dementia, characterized by an early olfactory dysfunction, progressive memory loss, and behavioral deterioration. Albeit substantial progress has been made in characterizing AD‐associated molecular cellular events, there unmet clinical need for new therapies. In this study, tract proteotyping performed controls AD subjects ( n = 17/group) showed a Braak stage‐dependent proteostatic impairment accompanied modulation amyloid...
Astrocytes are considered an essential source of blood-borne glucose or its metabolites to neurons. Nonetheless, the necessity main astrocyte transporter, i.e., GLUT1, for brain metabolism has not been defined. Unexpectedly, we found that was paradoxically augmented in mice with astrocytic GLUT1 reduction (GLUT1 ΔGFAP mice). These also exhibited improved peripheral especially obesity, rendering them metabolically healthier. Mechanistically, observed GLUT1-deficient astrocytes increased...