Pharmacological administration of the isoflavone daidzein enhances cell proliferation and reduces high fat diet-induced apoptosis and gliosis in the rat hippocampus.

Rivera, PatriciaPérez-Martín, MargaritaPavón, Francisco JSerrano, AntoniaCrespillo, AnaCifuentes, ManuelLópez-Ávalos, María-DoloresGrondona, Jesús MVida, MargaritaFernández-Llebrez, PedroRodríguez de Fonseca, FernandoSuárez, Juan2013-11-142013-11-142013-05-31Rivera P, Pérez-Martín M, Pavón FJ, Serrano A, Crespillo A, Cifuentes M, et al. Pharmacological administration of the isoflavone daidzein enhances cell proliferation and reduces high fat diet-induced apoptosis and gliosis in the rat hippocampus. PLoS ONE. 2013; 8(5):e64750http://hdl.handle.net/10668/1376Journal Article; Research Support, Non-U.S. Gov't;Soy extracts have been claimed to be neuroprotective against brain insults, an effect related to the estrogenic properties of isoflavones. However, the effects of individual isoflavones on obesity-induced disruption of adult neurogenesis have not yet been analyzed. In the present study we explore the effects of pharmacological administration of daidzein, a main soy isoflavone, in cell proliferation, cell apoptosis and gliosis in the adult hippocampus of animals exposed to a very high-fat diet. Rats made obese after 12-week exposure to a standard or high-fat (HFD, 60%) diets were treated with daidzein (50 mg kg(-1)) for 13 days. Then, plasma levels of metabolites and metabolic hormones, cell proliferation in the subgranular zone of the dentate gyrus (SGZ), and immunohistochemical markers of hippocampal cell apoptosis (caspase-3), gliosis (GFAP and Iba-1), food reward factor FosB and estrogen receptor alpha (ERα) were analyzed. Treatment with daidzein reduced food/caloric intake and body weight gain in obese rats. This was associated with glucose tolerance, low levels of HDL-cholesterol, insulin, adiponectin and testosterone, and high levels of leptin and 17β-estradiol. Daidzein increased the number of phospho-histone H3 and 5-bromo-2-deoxyuridine (BrdU)-ir cells detected in the SGZ of standard diet and HFD-fed rats. Daidzein reversed the HFD-associated enhanced immunohistochemical expression of caspase-3, FosB, GFAP, Iba-1 and ERα in the hippocampus, being more prominent in the dentate gyrus. These results suggest that pharmacological treatment with isoflavones regulates metabolic alterations associated with enhancement of cell proliferation and reduction of apoptosis and gliosis in response to high-fat diet.enAlimentos a base de sojaIsoflavonasProliferación celularHipocampoRatasAlimentación rica en grasaHormonasMedical Subject Headings::Technology, Industry, Agriculture::Food and Beverages::Food::Vegetables::Fabaceae::Soybeans::Soy FoodsMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Benzopyrans::Chromones::Flavonoids::IsoflavonesMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell ProliferationMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::ApoptosisMedical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::HippocampusMedical Subject Headings::Named Groups::Persons::Age Groups::AdultMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::RatsMedical Subject Headings::Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Diet::Diet, High-FatMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::HormonesMedical Subject Headings::Technology, Industry, Agriculture::Food and Beverages::FoodMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Receptors, Cytoplasmic and Nuclear::Receptors, Steroid::Receptors, Estrogen::Estrogen Receptor alphaMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Clinical Laboratory Techniques::Clinical Chemistry Tests::Blood Chemical Analysis::Glucose Tolerance TestMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Lipoproteins::Lipoproteins, HDL::Cholesterol, HDLMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pancreatic Hormones::InsulinsMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Adipokines::AdiponectinMedical Subject Headings::Chemicals and Drugs::Polycyclic Compounds::Steroids::Androstanes::Androstenes::Androstenols::TestosteroneMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Adipokines::LeptinMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Gonadal Hormones::Gonadal Steroid Hormones::Estradiol Congeners::EstradiolMedical Subject Headings::Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 1-Ring::Pyrimidines::Pyrimidine Nucleosides::Uridine::Deoxyuridine::BromodeoxyuridineMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Peptide Hydrolases::Cysteine Proteases::Cysteine Endopeptidases::Caspases::Caspases, Effector::Caspase 3Medical Subject Headings::Anatomy::Nervous System::Central Nervous System::Brain::Limbic System::Hippocampus::Dentate GyrusPharmacological administration of the isoflavone daidzein enhances cell proliferation and reduces high fat diet-induced apoptosis and gliosis in the rat hippocampus.research article23741384open access10.1371/journal.pone.00647501932-6203PMC3669353