A5010546788- Neuroscience and Neuropharmacology Research
- Alzheimer's disease research and treatments
- Genetics and Neurodevelopmental Disorders
- Neuroinflammation and Neurodegeneration Mechanisms
- Retinal Development and Disorders
- Ion channel regulation and function
- ATP Synthase and ATPases Research
- Modular Robots and Swarm Intelligence
- Mitochondrial Function and Pathology
- Receptor Mechanisms and Signaling
- Neurogenesis and neuroplasticity mechanisms
- Metabolism and Genetic Disorders
- Machine Learning in Materials Science
- Microtubule and mitosis dynamics
- Genetic and Kidney Cyst Diseases
- Neurological Disease Mechanisms and Treatments
- Glycogen Storage Diseases and Myoclonus
- Protein Kinase Regulation and GTPase Signaling
- Supramolecular Self-Assembly in Materials
- Amino Acid Enzymes and Metabolism
- Cellular transport and secretion
Centro de Biología Molecular Severo Ochoa
2020-2025
Neurocentre Magendie
2025
Inserm
2025
Universidad Autónoma de Madrid
2020-2025
Université de Bordeaux
2025
Centre for Biomedical Network Research on Rare Diseases
2024
Instituto de Investigación de Enfermedades Raras
2024
Consejo Superior de Investigaciones Científicas
2023
Astrocytes are known to modulate neuronal activity by gliotransmission and through metabolic regulation. However, the connection between these two processes is still poorly defined. In this work we show that p110α isoform of phosphatidylinositol 3-kinase (PI3K) in astrocytes required for long-term potentiation (LTP) has an impact on learning memory. Using a specific deletion from hippocampal adult mice, found LTP depends astrocytic sustain D-serine levels activation NMDA receptors during...
Abstract The small GTPase Ras is an intracellular signaling hub required for long-term potentiation (LTP) in the hippocampus and memory formation. Genetic alterations (i.e., RASopathies) are linked to cognitive disorders humans. However, it remains unclear how controls synaptic plasticity, whether different isoforms play overlapping or distinct roles neurons. Using genetically modified mice, we show here that H-Ras (the most abundant isoform brain) does not promote LTP, but instead...
Impaired neuronal and synaptic function are hallmarks of early Alzheimer's disease (AD), preceding other neuropathological traits cognitive decline. We previously showed that SFRP1, a glial-derived protein elevated in AD brains from preclinical stages, contributes to progression, implicating glial factors pathogenesis. Here, we generate analyze transgenic mice overexpressing astrocytic SFRP1. SFRP1 accumulation causes dendritic defects adult mice, followed by impaired long-term potentiation...
Article16 November 2020free access Source DataTransparent process GSK3α, not GSK3β, drives hippocampal NMDAR-dependent LTD via tau-mediated spine anchoring Jonathan E Draffin orcid.org/0000-0002-1686-8504 Centro de Biología Molecular Severo Ochoa, CSIC-Universidad Autónoma Madrid, Spain Search for more papers by this author Carla Sánchez-Castillo Alba Fernández-Rodrigo Xavier Sánchez-Sáez Jesús Ávila orcid.org/0000-0002-6288-0571 Florence F Wagner orcid.org/0000-0001-8981-0330 Stanley Center...
Neuronal connectivity and activity-dependent synaptic plasticity are fundamental properties that support brain function cognitive performance. Phosphatidylinositol 3-kinase (PI3K) intracellular signaling controls multiple mechanisms mediating neuronal growth, structure, plasticity. However, it is still unclear how these pleiotropic functions integrated at molecular cellular levels. To address this issue, we used neuron-specific virally delivered Cre expression to delete either p110α or p110β...
In this work, we tested the hypothesis that development of dementia in individuals with type 2 diabetes (T2DM) requires a genetic background predisposition to neurodegenerative disease. As proof concept, induced T2DM middle-aged hAPP NL/F mice, preclinical model Alzheimer’s We show produces more severe behavioral, electrophysiological, and structural alterations these mice compared wild-type mice. Mechanistically, deficits are not paralleled by higher levels toxic forms Aβ or...
The synaptic removal of AMPA-type glutamate receptors (AMPARs) is a core mechanism for hippocampal long-term depression (LTD). In this study, we address the role microtubule-dependent transport AMPARs as driver vesicular trafficking and sorting during LTD. Here, show that kinesin-1 motor KIF5A/C strictly required LTD expression in CA3-to-CA1 synapses. Specifically, find KIF5 an efficient internalization after NMDA receptor activation. We KIF5/AMPAR complex assembled activity-dependent manner...
Long-term synaptic plasticity is typically associated with morphological changes in connections. However, the molecular mechanisms coupling functional and structural aspects of are still poorly defined. The catalytic activity type I phosphoinositide-3-kinase (PI3K) required for specific forms plasticity, such as NMDA receptor-dependent long-term potentiation (LTP) mGluR-dependent depression (LTD). On other hand, PI3K signaling has been linked to neuronal growth synapse formation....
Abstract Decreased dendritic complexity and impaired synaptic function are strongly linked to cognitive decline in Alzheimer’s disease (AD), precede the emergence of other neuropathological traits that establish a harmful cycle exacerbating dysfunction. SFRP1, glial-derived protein regulating cell-cell communication, is abnormally elevated brain AD patients related mouse models already at early stages. Neutralization SFRP1 activity mice reduces occurrence aggregates, neuroinflammation...
Deficiencies in the electron transport chain (ETC) lead to mitochondrial diseases. While mutations are distributed across organism, cell and tissue sensitivity ETC disruption varies, molecular mechanisms underlying this variability remain poorly understood. Here we show that, upon inhibition, a non-canonical tricarboxylic acid (TCA) cycle upregulates maintain malate levels concomitant production of NADPH. Our findings indicate that adverse effects observed CI inhibition primarily stem from...
Abstract A significant number of individuals with type 2 diabetes (T2DM) develop cognitive deficits over time that in some cases could lead to dementia. It remains be identified the diabetes-related factors or comorbid conditions drive association and how they work. In this manuscript, we show 14-15 month-old hAPP NL/F mice, a knock‐in mouse model preclinical Alzheimer’s disease (AD) (that is, generate Aβ42 at an early age but do not symptoms until are old), wild type, behavioural correlate...