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E-GEOD-60388 - In vitro caloric restriction induces protective genes and functional rejuvenation in senescent SAMP8 astrocytes

Status
Released on 23 June 2015, last updated on 27 June 2015
Organism
Mus musculus
Samples (12)
Array (1)
Protocols (7)
Description
Astrocytes are key cells in brain aging, helping neurons to undertake healthy aging or otherwise letting them enter into a spiral of neurodegeneration. We aimed to characterize astrocytes cultured from senescence-accelerated prone 8 (SAMP8) mice, a mouse model of brain pathological aging, along with the effects of caloric restriction, the most effective rejuvenating treatment known so far. Analysis of the transcriptomic profiles of SAMP8 astrocytes cultured in control conditions and treated with caloric restriction serum was performed using mRNA microarrays. A decrease in mitochondrial and ribosome mRNA, which was restored by caloric restriction, confirmed the age-related profile of SAMP8 astrocytes and the benefits of caloric restriction. An amelioration of antioxidant and neurodegeneration-related path- ways confirmed the brain benefits of caloric restriction. Studies of oxidative stress and mitochondrial function demonstrated a reduction of oxidative damage and partial improvement of mito- chondria after caloric restriction. In summary, caloric restriction showed a significant tendency to normalize pathologically aged astrocytes through the activation of pathways that are protective against the age-related deterioration of brain physiology. Key words: astrocytes; caloric restriction; mitochondria; oxidative stress; RNA microarrays; SAMP8. Primary cultures enriched in astrocytes were obtained from cerebral cortical tissue from 2-day-old SAMP8 and SAMR1 mice. Astrocyte cultures were established and experiments were routinely carried out after 21 days in culture. Established astrocyte cultures of both SAMR1 and SAMP8 consisted of 85-90% astrocytes, 10-15% microglia and 0.1-1% oligodendroglia. Sera from rats subjected to ad libitum (AL) diet and to CR were obtained as described for the establishment of the CR in vitro model (de Cabo et al., 2003). Serum was heat inactivated at 56°C prior to use in astrocyte culture experiments. Treatment in vitro was performed by adding 10% volume CR or AL serum onto the astrocyte culture medium for 48 h, the cells were harvested and RNA was extracted for the microarray studies. Three biological replicates for each condition were done and RNA was extracted for the microarray studies. Please note that SAM models were developed from AKR/J by Kyoto University. Five litters with severe senescence were selected to further propagate and examine these characteristics. Litters that showed normal aging were selected as a senescence-resistant series (R-series). The genetic background of the SAM mice became suspect after the pathological findings were different from the AKR/J mouse. Each SAM model is genetically different. Each SAM colony was acquired by Harlan by Takeda Chemical Ltd. in 2002. And here is the link to the company site. http://www.harlan.com/products_and_services/research_models_and_services/research_models/sam_inbred_mice/samp8tahsd.hl
Experiment type
transcription profiling by array 
Contacts
Kevin G Becker <beckerk@grc.nia.nih.gov>, Coral Sanfeliu, Hector Palacios, Merce Pallas, Patricia Molina-Martınez, Rafael de Cabo, Rajib K Paul, Rosa Cristofol, Ruben Corpas, Silvia Garcıa-Matas, Vincent M Gutierrez
Citation
In vitro caloric restriction induces protective genes and functional rejuvenation in senescent SAMP8 astrocytes. Garc�a-Matas S, Paul RK, Molina-Mart�nez P, Palacios H, Gutierrez VM, Corpas R, Pallas M, Crist�fol R, de Cabo R, Sanfeliu C.
MIAME
PlatformsProtocolsVariablesProcessedRaw
Files
Investigation descriptionE-GEOD-60388.idf.txt
Sample and data relationshipE-GEOD-60388.sdrf.txt
Processed data (1)E-GEOD-60388.processed.1.zip
Additional data (1)E-GEOD-60388.additional.1.zip
Array designA-MEXP-932.adf.txt
Links