Publication: 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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Date
2015-03-27
Authors
Rivera, Patricia
Bindila, Laura
Pastor, Antoni
Pérez-Martín, Margarita
Pavón, Francisco J
Serrano, Antonia
de la Torre, Rafael
Lutz, Beat
Rodríguez de Fonseca, Fernando
Suárez, Juan
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Publisher
Frontiers Media
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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.
Description
Journal Article;
MeSH Terms
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Amidohydrolases
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis
Medical Subject Headings::Anatomy::Cells::Neuroglia::Astrocytes
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Benzamides
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxyuridine::Bromodeoxyuridine
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoids
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Carbamates
Medical Subject Headings::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 Death
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation
Medical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Steroids::Cholestanes::Cholestenes::Cholesterol
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amines::Amino Alcohols::Ethanolamines
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Gliosis
Medical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hypothalamus
Medical Subject Headings::Anatomy::Nervous System::Neuroglia::Microglia
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiation::Neurogenesis
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Monounsaturated::Oleic Acids
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Palmitic Acids
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats
Medical Subject Headings::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::Chemicals and Drugs::Lipids::Glycerides::Triglycerides
Medical Subject Headings::Organisms::Eukaryota::Animals
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::Apoptosis
Medical Subject Headings::Anatomy::Cells::Neuroglia::Astrocytes
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Benzamides
Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Body Constitution::Body Weights and Measures::Body Size::Body Weight
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxyuridine::Bromodeoxyuridine
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Hydrocarbons::Terpenes::Cannabinoids
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Carbamates
Medical Subject Headings::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 Death
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell Proliferation
Medical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Steroids::Cholestanes::Cholestenes::Cholesterol
Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids
Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amines::Amino Alcohols::Ethanolamines
Medical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Gliosis
Medical Subject Headings::Chemicals and Drugs::Carbohydrates::Monosaccharides::Hexoses::Glucose
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus
Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hypothalamus
Medical Subject Headings::Anatomy::Nervous System::Neuroglia::Microglia
Medical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiation::Neurogenesis
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Fatty Acids, Unsaturated::Fatty Acids, Monounsaturated::Oleic Acids
Medical Subject Headings::Chemicals and Drugs::Lipids::Fatty Acids::Palmitic Acids
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats
Medical Subject Headings::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::Chemicals and Drugs::Lipids::Glycerides::Triglycerides
DeCS Terms
CIE Terms
Keywords
URB597, FAAH, Cannabinoids, Energy metabolism, Neurogenesis, Gliosis, Bromodesoxiuridina, Cannabinoides, Carbamatos, Caspasa 3, Muerte celular, Proliferación celular, Colesterol, Endocannabinoides, Etanolaminas, Glucosa, Hipocampo, Hipotálamo, Microglía, Ácidos oléicos, Ácidos palmíticos, Ratas, Receptor cannabinoide CB1, Triglicéridos, Amidohidrolasas, Apoptosis, Astrocitos, Benzamidas, Peso corporal, Cerebro
Citation
Rivera 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; 9:98