A5045781715- Neuroinflammation and Neurodegeneration Mechanisms
- Neuroscience and Neuropharmacology Research
- Mitochondrial Function and Pathology
- Cancer, Hypoxia, and Metabolism
- Stress Responses and Cortisol
- Alzheimer's disease research and treatments
- Tryptophan and brain disorders
- Genetic Neurodegenerative Diseases
- Neurogenesis and neuroplasticity mechanisms
- Barrier Structure and Function Studies
- Adrenal and Paraganglionic Tumors
- Cell Image Analysis Techniques
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Brain Tumor Detection and Classification
- Cellular transport and secretion
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Intracerebral and Subarachnoid Hemorrhage Research
- Gene expression and cancer classification
- Neuroscience of respiration and sleep
- Epigenetics and DNA Methylation
- Amyotrophic Lateral Sclerosis Research
- Genomic variations and chromosomal abnormalities
- Ion channel regulation and function
University of Edinburgh
2020-2025
UK Dementia Research Institute
2020-2025
British Heart Foundation
2025
University of California, Los Angeles
2017-2023
Northwestern University
2016
Czech Academy of Sciences, Institute of Physiology
2016
Hospital Universitario Virgen del Rocío
2012-2015
Instituto de Biomedicina de Sevilla
2012-2015
Universidad de Sevilla
2012-2015
Biomedical Research Networking Center on Neurodegenerative Diseases
2012-2014
Astrocytes are ubiquitous in the brain and widely held to be largely identical. However, this view has not been fully tested, possibility that astrocytes neural circuit specialized remains unexplored. Here, we used multiple integrated approaches, including RNA sequencing (RNA-seq), mass spectrometry, electrophysiology, immunohistochemistry, serial block-face-scanning electron microscopy, morphological reconstructions, pharmacogenetics, diffusible dye, calcium, glutamate imaging, directly...
Astrocytes tile the entire CNS, but their functions within neural circuits in health and disease remain incompletely understood. We used genetically encoded Ca 2+ glutamate indicators to explore rules for astrocyte engagement corticostriatal circuit of adult wild-type (WT) Huntington's (HD) model mice at ages not accompanied by overt astrogliosis (at approximately postnatal days 70–80). WT striatal astrocytes displayed extensive spontaneous signals, did respond cortical stimulation, implying...
Astrocyte gene expression is altered in mouse models of Huntington’s disease and postmortem brain samples from patients with HD.
Astrocytes and neurons extensively interact in the brain. Identifying astrocyte neuron proteomes is essential for elucidating protein networks that dictate their respective contributions to physiology disease. Here we used cell-specific subcompartment-specific proximity-dependent biotinylation1 study of striatal astrocytes vivo. We evaluated cytosolic plasma membrane compartments discover how these cells differ at level signalling machinery. also assessed subcellular astrocytes, including...
Abstract Astrocytes support the energy demands of synaptic transmission and plasticity. Enduring changes in efficacy are highly sensitive to stress, yet whether astrocyte bioenergetic control synapses contributes stress-impaired plasticity is unclear. Here we show mice that stress constrains shuttling glucose lactate through networks, creating a barrier for neuronal access an astrocytic reservoir hippocampus neocortex, compromising long-term potentiation. Impairing delivery substrates by...
Astrocytic contributions to neuroinflammation are widely implicated in disease, but they remain incompletely explored. We assess medial prefrontal cortex (PFC) and visual (VCX) astrocyte whole-tissue gene expression changes mice following peripherally induced triggered by a systemic bacterial endotoxin, lipopolysaccharide, which produces sickness-related behaviors, including anhedonia. Neuroinflammation-mediated behavioral astrocyte-specific alterations peak when anhedonia is greatest then...
Significance The architecture of neuronal dendritic trees is crucial for brain connectivity, whereas abnormalities are associated with psychiatric disorders. Rare copy number variations (CNVs) a category mutations often schizophrenia, autism, and other mental However, the genetic complexity CNV disorders poses serious challenge identification experimentally approachable mechanisms. Here we used network analysis to identify most topologically important hub in protein–protein interaction...
The blood-brain barrier (BBB) plays a crucial role in maintaining brain homeostasis. During ageing, the BBB undergoes structural alterations. Electron microscopy (EM) is gold standard for studying alterations of vasculature. However, analysis EM images time-intensive and can be prone to selection bias, limiting our understanding effect ageing on BBB. Here, we introduce 3BTRON, deep learning framework automated architecture (the morphology, structure, texture its various components) images....
Age-associated vascular alterations make the brain more vulnerable to neuropathologies. Research in humans and rodents have demonstrated structural, molecular, functional of aged vasculature that suggest blood-brain barrier (BBB) dysfunction. However, these studies focused on particular features BBB specific regions. Thus, it remains unclear if which age-associated phenotypes are conserved across areas. Moreover, there is very limited information about how dysfunction cell-specific relate...
The SDHD gene (subunit D of succinate dehydrogenase) has been shown to be involved in the generation paragangliomas and pheochromocytomas. Loss heterozygosity normal allele is necessary for tumor transformation affected cells. As complete SdhD deletion lethal, we have generated mouse models carrying a "floxed" either an inducible (SDHD-ESR strain) or catecholaminergic tissue-specific (TH-SDHD CRE recombinase. Ablation both alleles adult SDHD-ESR mice did not result In contrast, carotid...
Astrocytes are essential components of neural circuits. They tile the entire central nervous system (CNS) and involved in a variety functions, which include neurotransmitter clearance, ion regulation, synaptic modulation, metabolic support to neurons, blood flow regulation. complex cells that have soma, several major branches, numerous fine processes contact diverse cellular elements within neuropil. In order assess morphology astrocytes, it is necessary reliable reproducible method...
Mutations in mitochondrial complex II (MCII; succinate dehydrogenase, Sdh) genes cause familiar pheochromocytoma/paraganglioma tumors. Several mechanisms have been proposed to account for Sdh-mutation-induced tumorigenesis, the most accepted of which is based on constitutive expression hypoxia-inducible factor 1α (Hif1α) at normal oxygen tension, a theory referred as "pseudo-hypoxic drive". Other molecular processes, such oxidative stress, apoptosis, or chromatin remodeling also play...
Cell-specific RNA sequencing has revolutionized the study of cell biology. Here, we present a protocol to assess cell-specific translatomes genetically targeted types. We focus on astrocytes and describe purification using RiboTag tools. Unlike single-cell sequencing, this approach allows high depth detect low expression genes, exploration RNAs translated in subcellular compartments. Furthermore, it avoids underestimation transcripts from cells susceptible isolation procedures. The can be...
Astrocytes are essential components of neural circuits. They tile the entire central nervous system (CNS) and involved in a variety functions, which include neurotransmitter clearance, ion regulation, synaptic modulation, metabolic support to neurons, blood flow regulation. complex cells that have soma, several major branches, numerous fine processes contact diverse cellular elements within neuropil. In order assess morphology astrocytes, it is necessary reliable reproducible method...
Abstract Astrocytes are widely implicated in CNS diseases, but their contributions to disease related phenotypes remain incompletely explored. Anhedonia accompanies several neurological and psychiatric including major depressive disorder (MDD) Alzheimer’s (AD), both of which associated with neuroinflammation. In order explore how neuroinflammation affects astrocytes, we assessed medial prefrontal cortex (PFC) visual (VCX) astrocytic gene expression using a mouse model that displayed...