title: Pharmacological administration of the isoflavone daidzein enhances cell proliferation and reduces high fat diet-induced apoptosis and gliosis in the rat hippocampus.
abstract: 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.
authors.affiliation: Laboratorio de Medicina Regenerativa (UGC Salud Mental), Instituto de Investigación Biomédica (IBIMA), Complejo Hospitalario de Málaga (Hospital Carlos Haya), Pabellón de Gobierno, Málaga, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Rivera
authors.forename: Margarita
authors.initials: M
authors.lastname: Pérez-Martín
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Pavón
authors.forename: Antonia
authors.initials: A
authors.lastname: Serrano
authors.forename: Ana
authors.initials: A
authors.lastname: Crespillo
authors.forename: Manuel
authors.initials: M
authors.lastname: Cifuentes
authors.forename: María-Dolores
authors.initials: MD
authors.lastname: López-Ávalos
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Grondona
authors.forename: Margarita
authors.initials: M
authors.lastname: Vida
authors.forename: Pedro
authors.initials: P
authors.lastname: Fernández-Llebrez
authors.forename: Fernando Rodríguez
authors.initials: FR
authors.lastname: de Fonseca
authors.forename: Juan
authors.initials: J
authors.lastname: Suárez
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D018891:Dentate Gyrus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects; D002149:Energy Intake / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005911:Gliosis / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D007529:Isoflavones / Q000302:isolation & purification / Q000494:pharmacology*; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000302:isolation & purification / Q000494:pharmacology*; D009765:Obesity / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D010936:Plant Extracts / Q000737:chemistry; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013025:Glycine max / Q000737:chemistry
chemical_list: C100745:Aif1 protein, rat; D002135:Calcium-Binding Proteins; D047628:Estrogen Receptor alpha; C483820:Fosb protein, rat; D005904:Glial Fibrillary Acidic Protein; D007529:Isoflavones; D008840:Microfilament Proteins; D018696:Neuroprotective Agents; D010936:Plant Extracts; D016760:Proto-Oncogene Proteins c-fos; C004742:daidzein; D053148:Caspase 3