Rivera, PatriciaBindila, LauraPastor, AntoniPérez-Martín, MargaritaPavón, Francisco JSerrano, Antoniade la Torre, RafaelLutz, BeatRodríguez de Fonseca, FernandoSuárez, Juan2016-08-092016-08-092015-03-27Rivera P, Bindila L, Pastor A, Pérez-Martín M, Pavón FJ, Serrano A, et al. Pharmacological blockade of the fatty acid amide hydrolase (FAAH) alters neural proliferation, apoptosis and gliosis in the rat hippocampus, hypothalamus and striatum in a negative energy context. Front Cell Neurosci. 2015; 9:98http://hdl.handle.net/10668/2340Journal Article;Endocannabinoids participate in the control of neurogenesis, neural cell death and gliosis. The pharmacological effect of the fatty acid amide hydrolase (FAAH) inhibitor URB597, which limits the endocannabinoid degradation, was investigated in the present study. Cell proliferation (phospho-H3(+) or BrdU(+) cells) of the main adult neurogenic zones as well as apoptosis (cleaved caspase-3(+)), astroglia (GFAP(+)), and microglia (Iba1(+) cells) were analyzed in the hippocampus, hypothalamus and striatum of rats intraperitoneally treated with URB597 (0.3 mg/kg/day) at one dose/4-days resting or 5 doses (1 dose/day). Repeated URB597 treatment increased the plasma levels of the N-acylethanolamines oleoylethanolamide, palmitoylethanolamide and arachidonoylethanolamine, reduced the plasma levels of glucose, triglycerides and cholesterol, and induced a transitory body weight decrease. The hippocampi of repeated URB597-treated rats showed a reduced number of phospho-H3(+) and BrdU(+) subgranular cells as well as GFAP(+), Iba1(+) and cleaved caspase-3(+) cells, which was accompanied with decreased hippocampal expression of the cannabinoid CB1 receptor gene Cnr1 and Faah. In the hypothalami of these rats, the number of phospho-H3(+), GFAP(+) and 3-weeks-old BrdU(+) cells was specifically decreased. The reduced striatal expression of CB1 receptor in repeated URB597-treated rats was only associated with a reduced apoptosis. In contrast, the striatum of acute URB597-treated rats showed an increased number of subventricular proliferative, astroglial and apoptotic cells, which was accompanied with increased Faah expression. Main results indicated that FAAH inhibitor URB597 decreased neural proliferation, glia and apoptosis in a brain region-dependent manner, which were coupled to local changes in Faah and/or Cnr1 expression and a negative energy context.enURB597FAAHCannabinoidsEnergy metabolismNeurogenesisGliosisBromodesoxiuridinaCannabinoidesCarbamatosCaspasa 3Muerte celularProliferación celularColesterolEndocannabinoidesEtanolaminasGlucosaHipocampoHipotálamoMicroglíaÁcidos oléicosÁcidos palmíticosRatasReceptor cannabinoide CB1TriglicéridosAmidohidrolasasApoptosisAstrocitosBenzamidasPeso corporalCerebroMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::AmidohydrolasesMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::ApoptosisMedical Subject Headings::Anatomy::Cells::Neuroglia::AstrocytesMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::BenzamidesMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body WeightMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::BrainMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxyuridine::BromodeoxyuridineMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::CannabinoidsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::CarbamatesMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins::CaspasesMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell DeathMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell ProliferationMedical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Steroids::Cholestanes::Cholestenes::CholesterolMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::EndocannabinoidsMedical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amines::Amino Alcohols::EthanolaminesMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::GliosisMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::GlucoseMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::HippocampusMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::HypothalamusMedical Subject Headings::Anatomy::Nervous System::Neuroglia::MicrogliaMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiation::NeurogenesisMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Monounsaturated::Oleic AcidsMedical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Palmitic AcidsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::RatsMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB1Medical Subject Headings::Chemicals and Drugs::Lipids::Glycerides::Triglyceridesresearch article25870539open access10.3389/fncel.2015.000981662-5102PMC4375993