0000000000039814

AUTHOR

Guilherme Horta

showing 5 related works from this author

Neurovascular EGFL7 regulates adult neurogenesis in the subventricular zone and thereby affects olfactory perception

2016

Adult neural stem cells reside in a specialized niche in the subventricular zone (SVZ). Throughout life they give rise to adult-born neurons in the olfactory bulb (OB), thus contributing to neural plasticity and pattern discrimination. Here, we show that the neurovascular protein EGFL7 is secreted by endothelial cells and neural stem cells (NSCs) of the SVZ to shape the vascular stem-cell niche. Loss of EGFL7 causes an accumulation of activated NSCs, which display enhanced activity and re-entry into the cell cycle. EGFL7 pushes activated NSCs towards quiescence and neuronal progeny towards differentiation. This is achieved by promoting Dll4-induced Notch signalling at the blood vessel-stem …

Male0301 basic medicineGeneral Physics and AstronomyNEURAL STEM-CELLSMOUSEMiceSUBEPENDYMAL ZONENeural Stem CellsLateral VentriclesLINEAGE PROGRESSIONBRAININ-VIVOMice KnockoutNeuronal PlasticityMultidisciplinaryCell CycleQNeurogenesisNICHEAnatomyNeural stem cellCell biologyAdult Stem Cellsmedicine.anatomical_structureSignal TransductionSTIMULATES NEUROGENESISEGF Family of ProteinsNeurogenesisScienceNotch signaling pathwaySubventricular zoneBiologyInhibitory postsynaptic potentialArticleGeneral Biochemistry Genetics and Molecular Biology03 medical and health sciencesNeuroplasticitymedicineBiological neural networkAnimalsCalcium-Binding ProteinsProteinsGeneral ChemistryOlfactory PerceptionENDOTHELIAL-CELLSnervous system diseasesOlfactory bulbMice Inbred C57BLSELF-RENEWAL030104 developmental biologynervous system
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Plasticity-Related Gene 1 Affects Mouse Barrel Cortex Function via Strengthening of Glutamatergic Thalamocortical Transmission

2016

Plasticity-related gene-1 (PRG-1) is a brain-specific protein that modulates glutamatergic synaptic transmission. Here we investigated the functional role of PRG-1 in adolescent and adult mouse barrel cortex both in vitro and in vivo. Compared with wild-type (WT) animals, PRG-1-deficient (KO) mice showed specific behavioral deficits in tests assessing sensorimotor integration and whisker-based sensory discrimination as shown in the beam balance/walking test and sandpaper tactile discrimination test, respectively. At P25-31, spontaneous network activity in the barrel cortex in vivo was higher in KO mice compared with WT littermates, but not at P16-19. At P16-19, sensory evoked cortical respo…

Male0301 basic medicinePatch-Clamp TechniquesCognitive NeuroscienceThalamusGlutamic AcidNerve Tissue ProteinsStimulationSensory systemWalkingNeurotransmissionBiologySomatosensory systempatch-clamp recordingsSynaptic TransmissionTissue Culture Techniques03 medical and health sciencesCellular and Molecular NeuroscienceGlutamatergic0302 clinical medicineThalamusNeural PathwaysNeuroplasticityAnimalsPostural BalanceMice KnockoutNeuronsNeuronal Plasticitybehaviorin vitroArticlesSomatosensory CortexBarrel cortexnetwork activityin vivo030104 developmental biologyTouch PerceptionVibrissaeCalmodulin-Binding ProteinsFemaleNeuroscience030217 neurology & neurosurgeryCerebral Cortex
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NECAB2 participates in an endosomal pathway of mitochondrial stress response at striatal synapses

2021

Synaptic signaling depends on ATP generated by mitochondria. Due to extensive connectivity, the striatum is especially vulnerable to mitochondrial dysfunction and thus requires efficient mitochondrial quality control. We found that the neuronal calcium-binding protein NECAB2 ensures synaptic function in the striatum by increasing mitochondrial efficiency. NECAB2 associates with early endosomes and mitochondria at striatal synapses. Loss of NECAB2 dysregulates proteins of the endosomal ESCRT machinery and oxidative phosphorylation. Mitochondria from NECAB2-deficient mice are more abundant but less efficient. These mitochondria exhibit increased respiration and superoxide production but produ…

Sensory gatingEndosomeChemistrySuperoxideOxidative phosphorylationStriatumMitochondrionmedicine.disease_causeCell biologychemistry.chemical_compoundmedicine.anatomical_structureddc:570medicineSynaptic signalingOxidative stress
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The K63 deubiquitinase CYLD modulates autism-like behaviors and hippocampal plasticity by regulating autophagy and mTOR signaling.

2021

Nondegradative ubiquitin chains attached to specific targets via Lysine 63 (K63) residues have emerged to play a fundamental role in synaptic function. The K63-specific deubiquitinase CYLD has been widely studied in immune cells and lately also in neurons. To better understand if CYLD plays a role in brain and synapse homeostasis, we analyzed the behavioral profile of CYLD-deficient mice. We found that the loss of CYLD results in major autism-like phenotypes including impaired social communication, increased repetitive behavior, and cognitive dysfunction. Furthermore, the absence of CYLD leads to a reduction in hippocampal network excitability, long-term potentiation, and pyramidal neuron s…

MaleAutism Spectrum DisorderNerve Tissue ProteinsHippocampal formationHippocampusDeubiquitinating enzymeSynapseMiceUbiquitinAutophagyAnimalsAutistic DisorderMechanistic target of rapamycinPI3K/AKT/mTOR pathwayNeuronsMultidisciplinarybiologyUbiquitinLysineTOR Serine-Threonine KinasesAutophagyMicrofilament ProteinsUbiquitinationLong-term potentiationBiological SciencesDeubiquitinating Enzyme CYLDMice Inbred C57BLSynapsesbiology.proteinFemaleNeuroscienceSignal TransductionProceedings of the National Academy of Sciences of the United States of America
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Molecular cause and functional impact of altered synaptic lipid signaling due to a prg‐1 gene SNP

2015

Loss of plasticity-related gene 1 (PRG-1), which regulates synaptic phospholipid signaling, leads to hyperexcitability via increased glutamate release altering excitation/inhibition (E/I) balance in cortical networks. A recently reported SNP in prg-1 (R345T/ mutPRG-1) affects ~5 million European and US citizens in a monoallelic variant. Our studies show that this mutation leads to a loss-of-PRG-1 function at the synapse due to its inability to control lysophosphatidic acid (LPA) levels via a cellular uptake mechanism which appears to depend on proper glycosylation altered by this SNP. PRG-1 +/ mice, which are animal correlates of human PRG-1 +/mut carriers, showed an altered cortical networ…

0301 basic medicineGeneticseducation.field_of_studySensory gatingPopulationGlutamate receptorLipid signalingBiologyCell biologySynapse03 medical and health scienceschemistry.chemical_compound030104 developmental biology0302 clinical medicinemedicine.anatomical_structurechemistryLysophosphatidic acidmedicineMolecular MedicineSignal transductionAutotaxineducation030217 neurology & neurosurgeryEMBO Molecular Medicine
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