6533b81ffe1ef96bd12785a0

RESEARCH PRODUCT

Pharmacological activation of CB2 receptors counteracts the deleterious effect of ethanol on cell proliferation in the main neurogenic zones of the adult rat brain.

Antonio VargasFernando Rodríguez De FonsecaFrancisco AlénFrancisco Javier PavónJuan SuárezAntonia SerranoBeat LutzEduardo BlancoLeticia RubioPatricia RiveraLaura Bindila

subject

:Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Morphogenesis::Embryonic and Fetal Development::Organogenesis::Neurogenesis [Medical Subject Headings]CB1 receptorTubulina (proteína)Cannabinoid receptorCarbamatosEtanol:Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Nuclear Proteins::Histones [Medical Subject Headings]Ventrículos lateralesSacarosaNeuronasSubgranular zone0302 clinical medicine: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:Chemicals and Drugs::Organic Chemicals::Carboxylic Acids::Acids Acyclic::Carbamates [Medical Subject Headings]Receptor cannabinoide CB1Cannabinoid receptor type 2:Organisms::Eukaryota::Animals [Medical Subject Headings]:Phenomena and Processes::Metabolic Phenomena::Metabolism::Phosphorylation [Medical Subject Headings]:Anatomy::Cells::Stem Cells::Neural Stem Cells [Medical Subject Headings]:Anatomy::Nervous System::Neurons [Medical Subject Headings]health care economics and organizations:Anatomy::Nervous System::Central Nervous System::Brain::Cerebral Ventricles::Lateral Ventricles [Medical Subject Headings]Original Research:Chemicals and Drugs::Nucleic Acids Nucleotides and Nucleosides::Nucleosides::Deoxyribonucleosides::Deoxyuridine::Bromodeoxyuridine [Medical Subject Headings]0303 health sciencesAlcoholismoalcoholConsumo de alcoholNeurogenesis: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]Endocannabinoid system3. Good healthbromodesoxiuridinaneurogenesisEndocannabinoidesmedicine.anatomical_structure:Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases [Medical Subject Headings]ACEADietaAlcoholFosforilaciónAgonistmedicine.medical_specialtyHidrolasasmedicine.drug_classNeurogenesiseducation:Psychiatry and Psychology::Mental Disorders::Substance-Related Disorders::Alcohol-Related Disorders::Alcoholism [Medical Subject Headings]Subventricular zoneBiology:Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet [Medical Subject Headings]:Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Telencephalon::Cerebrum::Cerebral Cortex::Hippocampus::Dentate Gyrus [Medical Subject Headings]lcsh:RC321-57103 medical and health sciencesCellular and Molecular NeuroscienceRatasInternal medicine:Chemicals and Drugs::Amino Acids Peptides and Proteins::Proteins::Nerve Tissue Proteins::Tubulin [Medical Subject Headings]JWH133medicineGiro dentadolcsh:Neurosciences. Biological psychiatry. Neuropsychiatry030304 developmental biologyCélulas madre nerviosas:Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Molecular Mechanisms of Pharmacological Action::Neurotransmitter Agents::Endocannabinoids [Medical Subject Headings]Dentate gyrusmarcadores genéticosCB2 receptor:Chemicals and Drugs::Carbohydrates::Polysaccharides::Oligosaccharides::Disaccharides::Sucrose [Medical Subject Headings]:Anatomy::Nervous System::Central Nervous System::Brain::Prosencephalon::Diencephalon::Hypothalamus [Medical Subject Headings]:Chemicals and Drugs::Organic Chemicals::Alcohols::Ethanol [Medical Subject Headings]Endocrinology:Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Rats [Medical Subject Headings]nervous system:Psychiatry and Psychology::Behavior and Behavior Mechanisms::Behavior::Drinking Behavior::Alcohol Drinking [Medical Subject Headings]:Chemicals and Drugs::Organic Chemicals::Amides::Benzamides [Medical Subject Headings]030217 neurology & neurosurgeryHipotálamoNeuroscience

description

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. 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 and SAF 2010-20521 to FR. Grant sponsor: Instituto de Salud Carlos III (ISCIII), Ministerio de Economía y Competitividad (MINECO), UE-ERDF. Grant number: CP12/03109 to JS. Grant sponsor: Red de Trastornos Adictivos, ISCIII, MINECO. Grant number: RD12/0028/0001 to FR. Grant sponsor: Plan Nacional Sobre Drogas, Ministerio de Sanidad y Consumo. Grant number: PNSD2010/143 to JS. Grant sponsor: Consejería de Economía, Innovación y Ciencia, Junta de Andalucía, UE/ERDF. Grant numbers: PI45403 and CTS-8221 to FR. Grant sponsor: Consejería de Salud, Junta de Andalucía, UE/ERDF. Grant numbers: SAS111224 to JS. Grant sponsor: German Research Foundation DFG. Grant number: FOR926, project CP to BL. JS, FP, and AS hold “Miguel Servet” research contracts from the National System of Health, ISCIII (grant numbers: CP12/03109, CP14/00212 and CP14/00173, respectively).

yearjournalcountryeditionlanguage
2015-09-29
10.3389/fncel.2015.00379https://hdl.handle.net/10668/2339