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Long-term Neuroglial Cocultures as a Brain Aging Model: Hallmarks of Senescence, MicroRNA Expression Profiles, and Comparison With In Vivo Models
- Source :
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences. 71:50-60
- Publication Year :
- 2015
- Publisher :
- Oxford University Press (OUP), 2015.
-
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.
- Subjects :
- Male
0301 basic medicine
Senescence
Aging
Transgene
Down-Regulation
Resveratrol
Biology
Histones
Mice
03 medical and health sciences
chemistry.chemical_compound
In vivo
microRNA
medicine
Animals
Cells, Cultured
Cellular Senescence
Interleukin-6
Gene Expression Profiling
Neurodegeneration
Brain
Neurodegenerative Diseases
beta-Galactosidase
medicine.disease
Coculture Techniques
In vitro
Astrogliosis
Cell biology
Mice, Inbred C57BL
Disease Models, Animal
MicroRNAs
Oxidative Stress
030104 developmental biology
chemistry
Geriatrics and Gerontology
Neuroglia
Biomarkers
Subjects
Details
- ISSN :
- 1758535X and 10795006
- Volume :
- 71
- Database :
- OpenAIRE
- Journal :
- The Journals of Gerontology Series A: Biological Sciences and Medical Sciences
- Accession number :
- edsair.doi.dedup.....fda7b3b6bbc70155a750013fc53924e8