0000000000003560

AUTHOR

Manuel Guzmán

0000-0001-7475-118x

showing 10 related works from this author

The CB1 cannabinoid receptor mediates excitotoxicity-induced neural progenitor proliferation and neurogenesis.

2007

Endocannabinoids are lipid signaling mediators that exert an important neuromodulatory role and confer neuroprotection in several types of brain injury. Excitotoxicity and stroke can induce neural progenitor (NP) proliferation and differentiation as an attempt of neuroregeneration after damage. Here we investigated the mechanism of hippocampal progenitor cell engagement upon excitotoxicity induced by kainic acid administration and the putative involvement of the CB1 cannabinoid receptor in this process. Adult NPs express kainate receptors that mediate proliferation and neurosphere generation in vitro via CB1 cannabinoid receptors. Similarly, in vivo studies showed that excitotoxicity-induce…

medicine.medical_specialtyKainic acidCannabinoid receptorNeurotoxinsExcitotoxicityKainate receptorBiologymedicine.disease_causeBiochemistryNeuroprotectionHippocampuschemistry.chemical_compoundMiceReceptor Cannabinoid CB1Epidermal growth factorInternal medicinemedicineAnimalsMolecular BiologyCell ProliferationMice KnockoutNeuronsKainic AcidStem CellsNeurogenesisCell BiologyEndocannabinoid systemCell biologyNerve RegenerationEndocrinologynervous systemchemistrylipids (amino acids peptides and proteins)Fibroblast Growth Factor 2The Journal of biological chemistry
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Singular Location and Signaling Profile of Adenosine A2A-Cannabinoid CB1 Receptor Heteromers in the Dorsal Striatum

2018

The dorsal striatum is a key node for many neurobiological processes such as motor activity, cognitive functions, and affective processes. The proper functioning of striatal neurons relies critically on metabotropic receptors. Specifically, the main adenosine and endocannabinoid receptors present in the striatum, ie, adenosine A(2A) receptor (A(2A)R) and cannabinoid CB1 receptor (CB1R), are of pivotal importance in the control of neuronal excitability. Facilitatory and inhibitory functional interactions between striatal A(2A)R and CB1R have been reported, and evidence supports that this cross-talk may rely, at least in part, on the formation of A(2A)R-CB1R heteromeric complexes. However, th…

0301 basic medicineCannabinoid receptorAdenosineReceptor Adenosine A2Amedicine.medical_treatmentAdenosinaAdenosine A2A receptormediated inhibitionStriatumBiologyhuntingtons-disease micecannabinoid CB1Mice03 medical and health sciencesglutamatergic neurotransmission0302 clinical medicineReceptor Cannabinoid CB1NeurobiologyNeural PathwaysBasal gangliamedicineAnimalsHumansendocannabinoid systemGenetically modified animalProtein Structure QuaternaryA(2A) receptorsPharmacologyEndocannabinoid systemCorpus Striatumprotein-coupled receptorsProtein SubunitsPsychiatry and Mental healthtransgenic mouse modelHuntington Disease030104 developmental biologyMetabotropic receptornervous systembasal gangliaCannabinoidallosteric interactionsNeuroscience030217 neurology & neurosurgeryNeurobiologiaSignal Transduction
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The CB1Cannabinoid Receptor Drives Corticospinal Motor Neuron Differentiation through the Ctip2/Satb2 Transcriptional Regulation Axis

2012

The generation and specification of pyramidal neuron subpopulations during development relies on a complex network of transcription factors. The CB1cannabinoid receptor is the major molecular target of endocannabinoids and marijuana active compounds. This receptor has been shown to influence neural progenitor proliferation and axonal growth, but its involvement in neuronal differentiation and the functional impact in the adulthood caused by altering its signaling during brain development are not known. Here we show that the CB1receptor, by preventing Satb2 (special AT-rich binding protein 2)-mediated repression, increased Ctip2 (COUP-TF interacting protein 2) promoter activity, and Ctip2-po…

Pyramidal tractsCannabinoid receptorGeneral Neurosciencemedicine.medical_treatmentCellular differentiationBiologyMotor neuronEndocannabinoid systemArticleGlutamatergicmedicine.anatomical_structurenervous systemCorticospinal tractmedicinelipids (amino acids peptides and proteins)CannabinoidNeuroscienceThe Journal of Neuroscience
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The endocannabinoid system controls food intake via olfactory processes

2014

Comment in Sensory systems: the hungry sense. [Nat Rev Neurosci. 2014] Inhaling: endocannabinoids and food intake. [Nat Neurosci. 2014]; International audience; Hunger arouses sensory perception, eventually leading to an increase in food intake, but the underlying mechanisms remain poorly understood. We found that cannabinoid type-1 (CB1) receptors promote food intake in fasted mice by increasing odor detection. CB1 receptors were abundantly expressed on axon terminals of centrifugal cortical glutamatergic neurons that project to inhibitory granule cells of the main olfactory bulb (MOB). Local pharmacological and genetic manipulations revealed that endocannabinoids and exogenous cannabinoid…

MaleOlfactory systemMESH: Olfactory PerceptionCannabinoid receptorMESH: Feedback Physiological[SDV]Life Sciences [q-bio]medicine.medical_treatmentMESH: Cannabinoid Receptor AgonistsMESH: EndocannabinoidsMESH: Receptor Cannabinoid CB1Synaptic TransmissionMESH: Mice KnockoutMESH: EatingEatingMiceOlfactory bulbReceptor Cannabinoid CB1MESH: AnimalsFeedback PhysiologicalMice Knockoutmusculoskeletal neural and ocular physiologyGeneral Neurosciencedigestive oral and skin physiologyOlfactory PathwaysEndocannabinoid systemMESH: Feeding Behaviorlipids (amino acids peptides and proteins)psychological phenomena and processesMESH: Olfactory BulbBiologyInhibitory postsynaptic potentialGlutamatergicMESH: Mice Inbred C57BLMESH: Synaptic TransmissionmedicineAnimalsMESH: MiceCannabinoid Receptor AgonistsFeeding BehaviorOlfactory PerceptionMESH: MaleOlfactory bulbMice Inbred C57BLnervous systemOdorFeeding behaviourCannabinoid[SDV.AEN]Life Sciences [q-bio]/Food and NutritionNeuroscienceMESH: Olfactory PathwaysEndocannabinoidsNature Neuroscience
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The CB1 cannabinoid receptor signals striatal neuroprotection via a PI3K/Akt/mTORC1/BDNF pathway

2015

The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. In particular, the CB1 receptor is highly expressed in the basal ganglia, mostly on terminals of medium-sized spiny neurons, where it plays a key neuromodulatory function. The CB1 receptor also confers neuroprotection in various experimental models of striatal damage. However, the assessment of the physiological relevance and therapeutic potential of the CB1 receptor in basal ganglia-related diseases is hampered, at least in part, by the lack of knowledge of the precise mechanism of CB1 receptor neuroprotective ac…

Brain-derived neurotrophic factormedicine.medical_specialtyCannabinoid receptormusculoskeletal neural and ocular physiologymedicine.medical_treatmentCell BiologyBiologyEndocannabinoid systemδ-opioid receptorEndocrinologynervous systemInternal medicinemedicinelipids (amino acids peptides and proteins)CannabinoidSignal transductionReceptorMolecular BiologyProtein kinase BNeuroscienceCell Death & Differentiation
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Prenatal exposure to cannabinoids evokes long-lasting functional alterations by targeting CB 1 receptors on developing cortical neurons

2015

The CB1 cannabinoid receptor, the main target of Δ(9)-tetrahydrocannabinol (THC), the most prominent psychoactive compound of marijuana, plays a crucial regulatory role in brain development as evidenced by the neurodevelopmental consequences of its manipulation in animal models. Likewise, recreational cannabis use during pregnancy affects brain structure and function of the progeny. However, the precise neurobiological substrates underlying the consequences of prenatal THC exposure remain unknown. As CB1 signaling is known to modulate long-range corticofugal connectivity, we analyzed the impact of THC exposure on cortical projection neuron development. THC administration to pregnant mice in…

cannabisBioquímicaCannabinoid receptorCB1 cannabinoid receptorNeurocienciasBrain Structure and FunctioncorticospinalBiologyMiceGlutamatergicReceptor Cannabinoid CB1Pregnancymental disordersmedicineAnimalsDronabinolReceptorseizuresCerebral CortexNeuronsMultidisciplinaryneurodevelopmentorganic chemicalsBiological SciencesMotor neuronmedicine.anatomical_structurenervous systemMaternal ExposureCerebral cortexForebrainGABAergicFemalelipids (amino acids peptides and proteins)NeuroscienceProceedings of the National Academy of Sciences
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Loss of striatal type 1 cannabinoid receptors is a key pathogenic factor in Huntington's disease.

2010

Endocannabinoids act as neuromodulatory and neuroprotective cues by engaging type 1 cannabinoid receptors. These receptors are highly abundant in the basal ganglia and play a pivotal role in the control of motor behaviour. An early downregulation of type 1 cannabinoid receptors has been documented in the basal ganglia of patients with Huntington's disease and animal models. However, the pathophysiological impact of this loss of receptors in Huntington's disease is as yet unknown. Here, we generated a double-mutant mouse model that expresses human mutant huntingtin exon 1 in a type 1 cannabinoid receptor-null background, and found that receptor deletion aggravates the symptoms, neuropatholog…

MaleHuntingtinCannabinoid receptorCell Survivalmedicine.medical_treatmentBlotting WesternMice TransgenicBiologyMotor ActivityGrowth Hormone-Releasing HormoneMiceReceptor Cannabinoid CB1medicineCannabinoid receptor type 2AnimalsDronabinolReceptorBrain-derived neurotrophic factorNeuronsAnalysis of VarianceReverse Transcriptase Polymerase Chain ReactionEndocannabinoid systemMagnetic Resonance ImagingCorpus StriatumHuntington DiseaseRotarod Performance TestGPR18Neurology (clinical)CannabinoidNeuroscienceBrain : a journal of neurology
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A restricted population of CB1 cannabinoid receptors with neuroprotective activity.

2014

The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. Of note, CB1 receptors are expressed at the synapses of two opposing (i.e., GABAergic/inhibitory and glutamatergic/excitatory) neuronal populations, so the activation of one and/or another receptor population may conceivably evoke different effects. Despite the widely reported neuroprotective activity of the CB1 receptor in animal models, the precise pathophysiological relevance of those two CB1 receptor pools in neurodegenerative processes is unknown. Here, we first induced excitotoxic damage in the mouse brain b…

MaleCannabinoid receptorPopulationNeurotoxinsExcitotoxicityGlutamic AcidBiologymedicine.disease_causeNeuroprotectionGlutamatergicMiceOrgan Culture TechniquesReceptor Cannabinoid CB1medicineAnimalsHumansGABAergic NeuronsReceptoreducationCaenorhabditis elegans ProteinsAgedCerebral CortexMice KnockoutNeuronseducation.field_of_studyMultidisciplinaryIntegrasesmusculoskeletal neural and ocular physiologyNeurodegenerative DiseasesBiological SciencesMiddle AgedReceptors GABA-AEndocannabinoid systemCorpus Striatumnervous systemGABAergiclipids (amino acids peptides and proteins)FemaleNeurosciencepsychological phenomena and processesEndocannabinoidsSynaptosomesProceedings of the National Academy of Sciences of the United States of America
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Loss of response of carnitine palmitoyltransferase I to okadaic acid in transformed hepatic cells

1998

The specific activity of carnitine palmitoyltransferase I (CPT-I) was similar in mitochondria isolated from rat Fao and human HepG2 hepatoma cells and from rat hepatocytes, but almost twofold higher in permeabilized hepatoma cells than in permeabilized hepatocytes. Short-term exposure to okadaic acid induced a ca. 80% stimulation of CPT-I in hepatocytes, whereas no significant response of the enzyme from hepatoma cells was evident. Thus, the high CPT-I activity displayed by hepatoma cells may be reached by hepatocytes upon challenge to okadaic acid. Reconstitution experiments with purified mitochondrial and cytoskeletal fractions showed that the cytoskeleton of hepatocytes produced a more r…

Carcinoma Hepatocellularendocrine system diseasesMitochondria LiverMitochondrionBiologyBiochemistrychemistry.chemical_compoundLiver Neoplasms ExperimentalOkadaic AcidTumor Cells CulturedmedicineAnimalsHumansheterocyclic compoundsCarnitine O-palmitoyltransferaseCytoskeletonneoplasmsCell Line TransformedPharmacologyCarnitine O-PalmitoyltransferaseLiver NeoplasmsOkadaic aciddigestive system diseasesMitochondriaRatsCell biologyKineticsmedicine.anatomical_structureBiochemistrychemistryCell cultureHepatocyteHepatic stellate cellCarnitine palmitoyltransferase IBiochemical Pharmacology
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The Endocannabinoid System Promotes Astroglial Differentiation by Acting on Neural Progenitor Cells

2006

Endocannabinoids exert an important neuromodulatory role via presynaptic cannabinoid CB1receptors and may also participate in the control of neural cell death and survival. The function of the endocannabinoid system has been extensively studied in differentiated neurons, but its potential role in neural progenitor cells remains to be elucidated. Here we show that the CB1receptor and the endocannabinoid-inactivating enzyme fatty acid amide hydrolase are expressed, bothin vitroandin vivo, in postnatal radial glia (RC2+cells) and in adult nestin type I (nestin+GFAP+) neural progenitor cells. Cell culture experiments show that CB1receptor activation increases progenitor proliferation and differ…

Cannabinoid receptorCellular differentiationMorpholinesApoptosisNerve Tissue ProteinsBiologyNaphthalenesHippocampusAmidohydrolasesNestinMiceIntermediate Filament ProteinsReceptor Cannabinoid CB1Cannabinoid Receptor ModulatorsGlial Fibrillary Acidic ProteinAnimalsProgenitor cellEnzyme InhibitorsNeural cellCells CulturedProgenitorMice KnockoutNeuronsCannabinoidsmusculoskeletal neural and ocular physiologyGeneral NeuroscienceStem CellsCell DifferentiationArticlesNestinEndocannabinoid systemNeural stem cellBenzoxazinesRatsnervous systemAstrocytesBenzamideslipids (amino acids peptides and proteins)CarbamatesNeurosciencepsychological phenomena and processesEndocannabinoids
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