A5089847940- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Cannabis and Cannabinoid Research
- Epilepsy research and treatment
- Neurogenesis and neuroplasticity mechanisms
- Receptor Mechanisms and Signaling
- Pancreatic function and diabetes
- Genetics and Neurodevelopmental Disorders
- Virus-based gene therapy research
- Tryptophan and brain disorders
- CRISPR and Genetic Engineering
- Biochemical effects in animals
- Phosphodiesterase function and regulation
- Neuroinflammation and Neurodegeneration Mechanisms
- Histone Deacetylase Inhibitors Research
- RNA regulation and disease
- Epigenetics and DNA Methylation
- Sirtuins and Resveratrol in Medicine
- Neurological disorders and treatments
- Cholinesterase and Neurodegenerative Diseases
- Nerve injury and regeneration
- Nuclear Receptors and Signaling
- Biochemical Acid Research Studies
- Zebrafish Biomedical Research Applications
- Forensic Toxicology and Drug Analysis
Universidad de Navarra
2010-2023
Navarre Institute of Health Research
2019-2021
University of the Basque Country
2016
ESPCI Paris
2013-2015
ParisTech
2013-2015
Centre de Gestion Scientifique
2015
Centre National de la Recherche Scientifique
2013-2015
Université Paris Sciences et Lettres
2015
Laboratoire Plasticité du Cerveau
2014
Zero to Three
2011
Abstract Alzheimer's disease (AD) and ageing are associated with impaired learning memory, recent findings point toward modulating chromatin remodeling through histone acetylation as a promising therapeutic strategy. Here we report that systemic administration of the HDAC inhibitor 4‐phenylbutyrate (PBA) reinstated fear in Tg2576 mouse model AD. mice develop age‐dependent amyloid pathology cognitive decline closely mimics progression humans. Memory reinstatement by PBA was observed...
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 Long-range coherences in spontaneous brain activity reflect functional connectivity. Here we propose a novel, highly resolved connectivity mapping approach, using ultrafast ultrasound (fUS), which enables imaging of cerebral microvascular haemodynamics deep the anaesthetized rodent brain, through large thinned-skull cranial window, with pixel dimensions 100 μm × in-plane. The millisecond-range temporal resolution allows unambiguous cancellation low-frequency cardio-respiratory...
Heteromerization of GPCRs is key to the integration extracellular signals and subsequent cell response via several mechanisms including heteromer-selective ligand binding, trafficking and/or downstream signalling. As lysophosphatidylinositol GPCR 55 (GPR55) has been shown affect function cannabinoid receptor subtype 2 (CB2 receptor) in human neutrophils, we investigated possible heteromerization CB2 receptors with GPR55.The direct interaction GPR55 heterologously expressed HEK293 cells was...
Synapse loss occurs early in Alzheimer's disease (AD) and is considered thebest pathological correlate of cognitive decline. Ephrins Eph receptorsare involved regulation excitatory neurotransmission play a rolein cytoskeleton remodeling
Endocannabinoids are recently recognized regulators of brain development, but molecular effectors downstream type-1 cannabinoid receptor (CB1R)-activation remain incompletely understood. We report atypical coupling neuronal CB1Rs, after activation by endo- or exocannabinoids such as the marijuana component ∆(9)-tetrahydrocannabinol, to heterotrimeric G12/G13 proteins that triggers rapid and reversible non-muscle myosin II (NM II) dependent contraction actomyosin cytoskeleton, through a...
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...
Dravet syndrome (DS), an intractable childhood epileptic encephalopathy with a high fatality rate, is typically caused by loss-of-function mutations in one allele of SCN1A, which encodes NaV1.1, 250-kDa voltage-gated sodium channel. In contrast to other epilepsies, pharmaceutical treatment for DS limited. Here, we demonstrate that viral vector-mediated delivery codon-modified SCN1A open reading frame into the brain improves comorbidities juvenile and adolescent mice (Scn1aA1783V/WT)....
4-Phenylbutyrate (PBA) is a histone deacetylase (HDAC) inhibitor whose efficacy in the Tg2576 mouse model of Alzheimer´s disease (AD) correlated with decreased tau phosphorylation, clearance intraneuronal Aβ and restoration dendritic spine density hippocampal CA1 pyramidal neurons. PBA also chemical chaperone that facilitates cell proteostasis. To determine relative contributions HDAC inhibition chaperone-like activity anti-AD effects PBA, we compared effect sodium butyrate (NaBu), an no...
The etiology of the more common (sporadic) forms Alzheimer's disease (AD) remains unknown, although age is most important risk factor. Nevertheless, interactions between environmental factors and genetic background may also influence
GPR40, the free fatty acid receptor 1, is expressed strongly in primate pancreas and brain. While role of pancreatic GPR40 glucose homeostasis has been extensively studied, absence this G-protein-coupled from brain rodents hampered studies into its central nervous system. However, we found intense mRNA expression by situ hybridization mouse hippocampal motor cortex neurons. Furthermore, a neuroblastoma cell was activated docosahexaenoic selective agonists, yet not palmitic acid....
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...
Neurons display important differences in plasma membrane composition between somatodendritic and axonal compartments, potentially leading to currently unexplored consequences G-protein-coupled-receptor signaling. Here, by using highly-resolved biosensor imaging measure local changes basal levels of key signaling components, we explored features type-1 cannabinoid receptor (CB1R) individual axons dendrites cultured rat hippocampal neurons. Activation endogenous CB1Rs led rapid, Gi/o-protein-...
Sirtuin 2 (SIRT2) has been associated to aging and age-related pathologies. Specifically, an age-dependent accumulation of isoform 3 SIRT2 in the CNS demonstrated; however, no study addressed behavioral or molecular consequences that this could have on aging. In present study, we designed adeno-associated virus vector (AAV-CAG-Sirt2.3-eGFP) for overexpression SIRT2.3 hippocampus month-old SAMR1 SAMP8 mice. Our results show specific does not induce significant effects at short long term...
Hippocampal neurogenesis, the process by which neural stem cells (NSC) continuously generate new neurons in dentate gyrus of most mammals including humans, is chiefly regulated neuronal activity. Thus, severe alterations have been found samples from epilepsy patients and hippocampal neurogenic niche mouse models epilepsy. Reactive-like gliogenic NSCs plus aberrant newborn with altered migration, morphology functional properties are induced seizures experimental temporal lobe neurogenesis...
We have recently reported cannabinoid-induced rapid changes in the structure of individual neurons. In order to investigate presence similar effects at regional level, measures brain tissue biomechanics are required. However, cannabinoids known alter cerebral blood flow (CBF), putatively resulting presently unexplored biomechanics. Here we used magnetic resonance elastography (MRE) and flow-sensitive alternating inversion recovery (FAIR) imaging measure vivo alterations mechanical properties...