title: A nutrigenomics approach for the study of anti-aging interventions: olive oil phenols and the modulation of gene and microRNA expression profiles in mouse brain.
abstract: OBJECTIVE
  Middle-aged C57Bl/6J mice fed for 6 months with extra-virgin olive oil rich in phenols (H-EVOO, phenol dose/day: 6 mg/kg) showed cognitive and motor improvement compared to controls fed the same olive oil deprived of phenolics (L-EVOO). The aim of the present study was to evaluate whether these behavioral modifications were associated with changes in gene and miRNA expression in the brain.
  
  
  METHODS
  Two brain areas involved in cognitive and motor processes were chosen: cortex and cerebellum. Gene and miRNA profiling were analyzed by microarray and correlated with performance in behavioral tests.
  
  
  RESULTS
  After 6 months, most of the gene expression changes were restricted to the cerebral cortex. The genes modulated by aging were mainly down-regulated, and the treatment with H-EVOO was associated with a significant up-regulation of genes compared to L-EVOO. Among those, we found genes previously associated with synaptic plasticity and with motor and cognitive behavior, such as Notch1, BMPs, NGFR, GLP1R and CRTC3. The agrin pathway was also significantly modulated. miRNAs were mostly up-regulated in old L-EVOO animals compared to young. However, H-EVOO-fed mice cortex displayed miRNA expression profiles similar to those observed in young mice. Sixty-three miRNAs, out of 1203 analyzed, were significantly down-regulated compared to the L-EVOO group; among them, we found miRNAs whose predicted target genes were up-regulated by the treatment, such as mir-484, mir-27, mir-137, mir-30, mir-34 and mir-124.
  
  
  CONCLUSIONS
  We are among the first to report that a dietary intervention starting from middle age with food rich in phenols can modulate at the central level the expression of genes and miRNAs involved in neuronal function and synaptic plasticity, along with cognitive, motor and emotional behavior.
authors.affiliation: Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139, Florence, Italy. cristina.luceri@unifi.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Luceri
authors.affiliation: Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bigagli
authors.affiliation: Chiesi Pharmaceuticals S.p.A., Parma, Italy.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pitozzi
authors.affiliation: Section of Pharmacology and Toxicology, Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), University of Florence, Viale Pieraccini 6, 50139, Florence, Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Giovannelli
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002531:Cerebellum / Q000254:growth & development / Q000378:metabolism; D002540:Cerebral Cortex / Q000254:growth & development / Q000378:metabolism*; D000066492:Cognitive Aging; D060825:Cognitive Dysfunction / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D019587:Dietary Supplements; D063427:Food Quality; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D018697:Nootropic Agents / Q000627:therapeutic use*; D054647:Nutrigenomics / Q000379:methods; D000069463:Olive Oil / Q000627:therapeutic use; D010636:Phenols / Q000627:therapeutic use*; D011596:Psychomotor Disorders / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D011597:Psychomotor Performance; D011897:Random Allocation
chemical_list: D035683:MicroRNAs; D009419:Nerve Tissue Proteins; D018697:Nootropic Agents; D000069463:Olive Oil; D010636:Phenols
keywords: Aging brain; Genomics; Nutraceuticals; Phenolic compounds; miRNomics