Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain
Copyright policy )Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain
Chronic alcohol exposure reduces endocannabinoid activity and disrupts adult neurogenesis in rodents, which results in structural and functional alterations. Cannabinoid receptor agonists promote adult neural progenitor cell (NPC) proliferation. We evaluated the protective effects of the selective CB1 receptor agonist ACEA, the selective CB2 receptor agonist JWH133 and the fatty-acid amide-hydrolase (FAAH) inhibitor URB597, which enhances endocannabinoid receptor activity, on NPC proliferation in rats with forced consumption of ethanol (10%) or sucrose liquid diets for 2 weeks. We performed immunohistochemical and stereological analyses of cells expressing the mitotic phosphorylation of histone-3 (phospho-H3+) and the replicating cell DNA marker 5-bromo-2'-deoxyuridine (BrdU+) in the main neurogenic zones of adult brain: subgranular zone of dentate gyrus (SGZ), subventricular zone of lateral ventricles (SVZ) and hypothalamus. Animals were allowed ad libitum ethanol intake (7.3 ± 1.1 g/kg/day) after a controlled isocaloric pair-feeding period of sucrose and alcoholic diets. Alcohol intake reduced the number of BrdU+ cells in SGZ, SVZ, and hypothalamus. The treatments (URB597, ACEA, JWH133) exerted a differential increase in alcohol consumption over time, but JWH133 specifically counteracted the deleterious effect of ethanol on NPC proliferation in the SVZ and SGZ, and ACEA reversed this effect in the SGZ only. JWH133 also induced an increased number of BrdU+ cells expressing neuron-specific β3-tubulin in the SVZ and SGZ. These results indicated that the specific activation of CB2 receptors rescued alcohol-induced impaired NPC proliferation, which is a potential clinical interest for the risk of neural damage in alcohol dependence.
:Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Morphogenesis::Embryonic and Fetal Development::Organogenesis::Neurogenesis [Medical Subject Headings], Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Carbamates, Sucrose, Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Morphogenesis::Embryonic and Fetal Development::Organogenesis::Neurogenesis, Carbamatos, Etanol, Hydrolases, Neuronas, Histones, Receptor, Cannabinoid, CB2, Neural Stem Cells, Receptor, Cannabinoid, CB1, :Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Carbamates [Medical Subject Headings], :Organisms::Eukaryota::Animals [Medical Subject Headings], :Anatomy::Cells::Stem Cells::Neural Stem Cells [Medical Subject Headings], :Anatomy::Nervous System::Neurons [Medical Subject Headings], :Anatomy::Nervous System::Central Nervous System::Brain::Cerebral Ventricles::Lateral Ventricles [Medical Subject Headings], alcohol, Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids, :Phenomena and Processes::Genetic Phenomena::Phenotype::Genetic Markers [Medical Subject Headings], :Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Cannabinoid Receptor Modulators::Cannabinoid Receptor Agonists [Medical Subject Headings], Benzamidas, :Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB2 [Medical Subject Headings], bromodesoxiuridina, Endocannabinoides, :Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases [Medical Subject Headings], Medical Subject Headings::Anatomy::Cells::Stem Cells::Neural Stem Cells, ACEA, Dieta, Fosforilación, Genetic Markers, Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue Proteins::Tubulin, Hidrolasas, Alcohol Drinking, Neurogenesis, :Psychiatry and Psychology::Mental Disorders::Substance-Related Disorders::Alcohol-Related Disorders::Alcoholism [Medical Subject Headings], Hypothalamus, :Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Hippocampus::Dentate Gyrus [Medical Subject Headings], Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Hippocampus::Dentate Gyrus, Giro dentado, Medical Subject Headings::Chemicals and Drugs::Carbohydrates::Polysaccharides::Oligosaccharides::Disaccharides::Sucrose, Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Cannabinoid Receptor Modulators::Cannabinoid Receptor Agonists, Medical Subject Headings::Psychiatry and Psychology::Mental Disorders::Substance-Related Disorders::Alcohol-Related Disorders::Alcoholism, Ethanol, marcadores genéticos, CB2 receptor, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype::Genetic Markers, :Chemicals and Drugs::Carbohydrates::Polysaccharides::Oligosaccharides::Disaccharides::Sucrose [Medical Subject Headings], :Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings], :Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats, Carbamates, :Chemicals and Drugs::Organic Chemicals::Amides::Benzamides [Medical Subject Headings], Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Diencephalon::Hypothalamus, Neuroscience, Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases, CB1 receptor, Tubulina (proteína), :Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins::Histones [Medical Subject Headings], Ventrículos laterales, Sacarosa, Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet, :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], Histonas, Tubulin, Receptor cannabinoide CB1, Lateral Ventricles, Medical Subject Headings::Anatomy::Nervous System::Neurons, Phosphorylation, :Phenomena and Processes::Metabolic Phenomena::Metabolism::Phosphorylation [Medical Subject Headings], :Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxyuridine::Bromodeoxyuridine [Medical Subject Headings], Alcoholismo, Consumo de alcohol, 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, CB2, 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::Organisms::Eukaryota::Animals, Alcoholism, Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Phosphorylation, Benzamides, Alcohol, RC321-571, Neurosciences. Biological psychiatry. Neuropsychiatry, :Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Benzamides, Ratas, :Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue Proteins::Tubulin [Medical Subject Headings], JWH133, Animals, Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Cerebral Ventricles::Lateral Ventricles, Células madre nerviosas, Cannabinoid Receptor Agonists, :Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids [Medical Subject Headings], Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins::Histones, Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking, :Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Diencephalon::Hypothalamus [Medical Subject Headings], Diet, Rats, :Chemicals and Drugs::Organic Chemicals::Alcohols::Ethanol [Medical Subject Headings], Bromodeoxyuridine, Dentate Gyrus, Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxyuridine::Bromodeoxyuridine, Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Alcohols::Ethanol, Hipotálamo, Endocannabinoids
:Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Morphogenesis::Embryonic and Fetal Development::Organogenesis::Neurogenesis [Medical Subject Headings], Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Carbamates, Sucrose, Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Morphogenesis::Embryonic and Fetal Development::Organogenesis::Neurogenesis, Carbamatos, Etanol, Hydrolases, Neuronas, Histones, Receptor, Cannabinoid, CB2, Neural Stem Cells, Receptor, Cannabinoid, CB1, :Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids, Acyclic::Carbamates [Medical Subject Headings], :Organisms::Eukaryota::Animals [Medical Subject Headings], :Anatomy::Cells::Stem Cells::Neural Stem Cells [Medical Subject Headings], :Anatomy::Nervous System::Neurons [Medical Subject Headings], :Anatomy::Nervous System::Central Nervous System::Brain::Cerebral Ventricles::Lateral Ventricles [Medical Subject Headings], alcohol, Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids, :Phenomena and Processes::Genetic Phenomena::Phenotype::Genetic Markers [Medical Subject Headings], :Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Cannabinoid Receptor Modulators::Cannabinoid Receptor Agonists [Medical Subject Headings], Benzamidas, :Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Membrane Proteins::Receptors, Cell Surface::Receptors, G-Protein-Coupled::Receptors, Cannabinoid::Receptor, Cannabinoid, CB2 [Medical Subject Headings], bromodesoxiuridina, Endocannabinoides, :Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases [Medical Subject Headings], Medical Subject Headings::Anatomy::Cells::Stem Cells::Neural Stem Cells, ACEA, Dieta, Fosforilación, Genetic Markers, Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue Proteins::Tubulin, Hidrolasas, Alcohol Drinking, Neurogenesis, :Psychiatry and Psychology::Mental Disorders::Substance-Related Disorders::Alcohol-Related Disorders::Alcoholism [Medical Subject Headings], Hypothalamus, :Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Hippocampus::Dentate Gyrus [Medical Subject Headings], Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Hippocampus::Dentate Gyrus, Giro dentado, Medical Subject Headings::Chemicals and Drugs::Carbohydrates::Polysaccharides::Oligosaccharides::Disaccharides::Sucrose, Medical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Cannabinoid Receptor Modulators::Cannabinoid Receptor Agonists, Medical Subject Headings::Psychiatry and Psychology::Mental Disorders::Substance-Related Disorders::Alcohol-Related Disorders::Alcoholism, Ethanol, marcadores genéticos, CB2 receptor, Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Phenotype::Genetic Markers, :Chemicals and Drugs::Carbohydrates::Polysaccharides::Oligosaccharides::Disaccharides::Sucrose [Medical Subject Headings], :Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings], :Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings], Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats, Carbamates, :Chemicals and Drugs::Organic Chemicals::Amides::Benzamides [Medical Subject Headings], Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Diencephalon::Hypothalamus, Neuroscience, Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases, CB1 receptor, Tubulina (proteína), :Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins::Histones [Medical Subject Headings], Ventrículos laterales, Sacarosa, Medical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet, :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], Histonas, Tubulin, Receptor cannabinoide CB1, Lateral Ventricles, Medical Subject Headings::Anatomy::Nervous System::Neurons, Phosphorylation, :Phenomena and Processes::Metabolic Phenomena::Metabolism::Phosphorylation [Medical Subject Headings], :Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxyuridine::Bromodeoxyuridine [Medical Subject Headings], Alcoholismo, Consumo de alcohol, 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, CB2, 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::Organisms::Eukaryota::Animals, Alcoholism, Medical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Phosphorylation, Benzamides, Alcohol, RC321-571, Neurosciences. Biological psychiatry. Neuropsychiatry, :Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings], Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Amides::Benzamides, Ratas, :Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nerve Tissue Proteins::Tubulin [Medical Subject Headings], JWH133, Animals, Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Cerebral Ventricles::Lateral Ventricles, Células madre nerviosas, Cannabinoid Receptor Agonists, :Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids [Medical Subject Headings], Medical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Nuclear Proteins::Histones, Medical Subject Headings::Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking, :Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Diencephalon::Hypothalamus [Medical Subject Headings], Diet, Rats, :Chemicals and Drugs::Organic Chemicals::Alcohols::Ethanol [Medical Subject Headings], Bromodeoxyuridine, Dentate Gyrus, Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxyuridine::Bromodeoxyuridine, Medical Subject Headings::Chemicals and Drugs::Organic Chemicals::Alcohols::Ethanol, Hipotálamo, Endocannabinoids
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).23 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Average impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!