1. 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
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Antonia Serrano, Margarita Pérez-Martín, Francisco Javier Pavón, Juan Suárez, Rafael de la Torre, Beat Lutz, Antoni Pastor, Fernando Rodríguez de Fonseca, Patricia Rivera, Laura Bindila, [Rivera,P, Pavón,FJ, Serrano,A, Rodríguez de Fonseca,F, Suárez,J] UGC Salud Mental, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga-Hospital Universitario Regional de Málaga, Málaga, Spain. [Rivera,P, de la Torre,R, Suárez,J] CIBER OBN, Instituto de Salud Carlos III, Madrid, Spain. [Bindila,L, Lutz,B] Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg-University of Mainz, Mainz, Germany. [Pastor,A, de la Torre,R] Institut Hospital del Mar d'Investigacions Mediques, Barcelona, Spain. [Pastor,A] Facultat de Medicina, Universitat Autonoma de Barcelona, Barcelona, Spain. [Pérez-Martín,M] Departamento de Biología Celular, Genética y Fisiología, Instituto de Investigación Biomédica (IBIMA), Universidad de Málaga, Málaga, Spain. [de la Torre, R] Facultat de Ciencies de la Salut i de la Vida, Universitat Pompeu Fabra (CEXS-UPF), Barcelona, Spain., Grant sponsor: 7th Framework Programme of European Union, Grant number: HEALTH-F2-2008-223713, REPROBESITY to FR and BL, Grant sponsor: Ministerio de Ciencia e Innovación, Grant numbers: SAF2010-19087, SAF 2010-20521, Grant sponsor: Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, UE-ERDF, Grant number: CP12/03109, Grant sponsor: Red de Trastornos Adictivos, Grant numbers: RD12/0028/0001, RD12/0028/0009, Grant sponsor: CIBERobn, Grant sponsor: Plan Nacional Sobre Drogas, Ministerio de Sanidad y Consumo, Grant number: PNSD2010/143, Grant sponsor: Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, UE/ERDF, Grant numbers: CTS-433, P-11-CVI-07637, Grant sponsor: Consejería de Salud, Junta de Andalucía, Grant numbers: PI0232/2008, PI0029/2008, SAS111224, Grant sponsor: Fundació La Marató de TV3, Grant number: 386/C/2011, Grant sponsor: German Research Foundation DFG, and Grant number: FOR629, project CP2 to BL. JS, FP, and AS hold 'Miguel Servet' research contracts from the National System of Health, ISCIII (Grant numbers: CP12/03109, CP14/00212, CP14/00173 respectively).
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Astrocitos ,Neurobiologia del desenvolupament ,Amidohidrolasas ,Cannabinoid receptor ,Carbamatos ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Intracellular Signaling Peptides and Proteins::Apoptosis Regulatory Proteins::Caspases [Medical Subject Headings] ,Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiation::Neurogenesis [Medical Subject Headings] ,medicine.medical_treatment ,Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose [Medical Subject Headings] ,Apoptosis ,Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight [Medical Subject Headings] ,chemistry.chemical_compound ,Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB1 [Medical Subject Headings] ,0302 clinical medicine ,Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Carbamates [Medical Subject Headings] ,Fatty acid amide hydrolase ,Receptor cannabinoide CB1 ,Organisms::Eukaryota::Animals [Medical Subject Headings] ,FAAH ,Gliosis ,health care economics and organizations ,Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxyuridine::Bromodeoxyuridine [Medical Subject Headings] ,Chemicals and Drugs::Lipids::Glycerides::Triglycerides [Medical Subject Headings] ,Original Research ,0303 health sciences ,Neurogenesis ,Benzamidas ,Chemicals and Drugs::Polycyclic Compounds::Steroids::Cholestanes::Cholestenes::Cholesterol [Medical Subject Headings] ,Endocannabinoid system ,Etanolaminas ,3. Good health ,Endocannabinoides ,Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Monounsaturated::Oleic Acids [Medical Subject Headings] ,Cannabinoides ,Microglía ,lipids (amino acids, peptides, and proteins) ,medicine.symptom ,Colesterol ,Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoids [Medical Subject Headings] ,Chemicals and Drugs::Lipids::Fatty Acids::Palmitic Acids [Medical Subject Headings] ,psychological phenomena and processes ,Proliferación celular ,medicine.medical_specialty ,Cerebro ,education ,Biology ,Bromodesoxiuridina ,Anatomy::Nervous System::Neuroglia::Microglia [Medical Subject Headings] ,Triglicéridos ,lcsh:RC321-571 ,Ácidos oléicos ,Ratas ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Internal medicine ,Hipocampo ,medicine ,Caspasa 3 ,Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus [Medical Subject Headings] ,Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation [Medical Subject Headings] ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,030304 developmental biology ,Palmitoylethanolamide ,Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids [Medical Subject Headings] ,Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases [Medical Subject Headings] ,Cannabinoids ,Anatomy::Cells::Neuroglia::Astrocytes [Medical Subject Headings] ,Peso corporal ,Energy metabolism ,Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings] ,Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hypothalamus [Medical Subject Headings] ,URB597 ,Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death [Medical Subject Headings] ,Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Gliosis [Medical Subject Headings] ,Chemicals and Drugs::Organic Chemicals::Amines::Amino Alcohols::Ethanolamines [Medical Subject Headings] ,Muerte celular ,Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis [Medical Subject Headings] ,Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings] ,Endocrinology ,chemistry ,nervous system ,Glucosa ,Cannabinoid ,Energy Metabolism ,Chemicals and Drugs::Organic Chemicals::Amides::Benzamides [Medical Subject Headings] ,Hipotálamo ,Ácidos palmíticos ,030217 neurology & neurosurgery ,Neuroscience - Abstract
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. Grant sponsor: 7th Framework Programme of European Union; Grant number: HEALTH-F2-2008-223713, REPROBESITY to FR and BL; Grant sponsor: Ministerio de Ciencia e Innovación; Grant numbers: SAF2010-19087, SAF 2010-20521; Grant sponsor: Instituto de Salud Carlos III, Ministerio de Economía y Competitividad, UE-ERDF; Grant number: CP12/03109; Grant sponsor: Red de Trastornos Adictivos; Grant numbers: RD12/0028/0001, RD12/0028/0009; Grant sponsor: CIBERobn; Grant sponsor: Plan Nacional Sobre Drogas, Ministerio de Sanidad y Consumo; Grant number: PNSD2010/143; Grant sponsor: Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, UE/ERDF; Grant numbers: CTS-433, P-11-CVI-07637; Grant sponsor: Consejería de Salud, Junta de Andalucía; Grant numbers: PI0232/2008, PI0029/2008, SAS111224; Grant sponsor: Fundació La Marató de TV3; Grant number: 386/C/2011; Grant sponsor: German Research Foundation DFG; Grant number: FOR629, project CP2 to BL. JS, FP, and AS hold “Miguel Servet” research contracts from the National System of Health, ISCIII (Grant numbers: CP12/03109, CP14/00212, CP14/00173 respectively).
- Published
- 2015
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