title: Long-term Neuroglial Cocultures as a Brain Aging Model: Hallmarks of Senescence, MicroRNA Expression Profiles, and Comparison With In Vivo Models.
abstract: Our purpose was to evaluate long-term neuroglial cocultures as a model for investigating senescence in the nervous system and to assess its similarities with in vivo models. To this aim, we maintained the cultures from 15 days in vitro (mature cultures) up to 27 days in vitro (senescent cultures), measuring senescence-associated, neuronal, dendritic, and astrocytic markers. Whole microRNA expression profiles were compared with those measured in the cortex of 18- and 24-month-old C57Bl/6J aged mice and of transgenic TgCRND8 mice, a model of amyloid-β deposition. Neuroglial cocultures displayed features of cellular senescence (increased senescence-associated-β-galactosidase activity, oxidative stress, γ-H2AX expression, IL-6 production, astrogliosis) that were concentration dependently counteracted by the antiaging compound resveratrol (1-5 µM). Among the 1,080 microRNAs analyzed, 335 were downregulated or absent in 27 compared with 15 days in vitro and resveratrol reversed this effect. A substantial overlapping was found between age-associated changes in microRNA expression profiles in vitro and in TgCRND8 mice but not in physiologically aged mice, indicating that this culture model displays more similarities with pathological than physiological brain aging. Our results demonstrate that neuroglial cocultures aged in vitro can be useful for investigating the cellular and molecular mechanisms of brain aging and for preliminary testing of protective compounds.
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology and elisabetta.bigagli@unifi.it.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Bigagli
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology and.
authors.forename: Cristina
authors.initials: C
authors.lastname: Luceri
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.
authors.forename: Tania
authors.initials: T
authors.lastname: Scartabelli
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology and.
authors.forename: Piero
authors.initials: P
authors.lastname: Dolara
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology and.
authors.forename: Fiorella
authors.initials: F
authors.lastname: Casamenti
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Florence, Italy.
authors.forename: Domenico E
authors.initials: DE
authors.lastname: Pellegrini-Giampietro
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health (NEUROFARBA), Section of Pharmacology and Toxicology and.
authors.forename: Lisa
authors.initials: L
authors.lastname: Giovannelli
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D018920:Coculture Techniques / Q000379:methods; D004195:Disease Models, Animal; D015536:Down-Regulation; D020869:Gene Expression Profiling; D006657:Histones / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000032:analysis*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000473:pathology; D009457:Neuroglia / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D015415:Biomarkers; D006657:Histones; D015850:Interleukin-6; D035683:MicroRNAs; C475961:gamma-H2AX protein, mouse; D001616:beta-Galactosidase
keywords: Aging; Microarray; Neurodegeneration.; Neuroglial cocultures; miRNA