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Series GSE50873 Query DataSets for GSE50873
Status Public on Jan 17, 2014
Title AMPK agonist AICAR improves cognition and motor coordination in young and aged mice
Organism Mus musculus
Experiment type Expression profiling by array
Summary Normal aging can result in a decline of memory and muscle function. Exercise may prevent or delay these changes. However, aging associated frailty may preclude physical activity. AMP-activated protein kinase (AMPK) is a transcriptional regulator important for muscle physiology. In the present study we investigated effects of AMPK agonist 5-aminoimidazole-4-carboxamide riboside (AICAR) on memory and motor function in young (2-month-old), aged (23-month-old) C57Bl/6 mice, and transgenic mice with muscle-specific mutated AMPK alpha-subunit (AMPK-DN). Mice were injected with AICAR (500 mg/kg) for 3 to 14 days and tested in the Morris water maze, rotarod and open field. Improved water maze performance and motor function was observed, albeit at longer duration of administration, in aged (14 days AICAR) than young (3 days AICAR) mice. In the AMPKDN mice, the compound did not enhance behavior, providing support for a muscle mediated mechanism. In addition, microarray analysis of muscle and hippocampal tissue derived from aged mice treated with AICAR revealed changes in gene expression in both tissues, which correlated with behavioral effects in a dose-dependent manner. Pronounced up-regulation of mitochondrial genes in muscle was observed. In the hippocampus genes relevant to neuronal development and plasticity were enriched. Altogether, endurance related factors may mediate both muscle and brain health in aging, and could play a role in new therapeutic interventions.
Key words: Skeletal Muscle, Brain, Exercise, AMPK, Learning and Memory, Morris water maze
 
Overall design 23-month old female C57BL/6J mice (Jackson Laboratory, Bar Harbor, ME) were housed under standard conditions, 3 mice per cage, with food and water ad libitum. Mice were injected intraperitoneally with 5-Aminoimidazole-4-carboxamide-1-a-D-ribofuranoside (AICAR, Toronto Research Chemicals Inc., Canada) dissolved in saline, 500 mg/kg/day for 3 (ACR3), 7 (ACR7) or 14 (ACR14) days or saline vehicle, for 3 (CTR) days. Thirty-three days after the final injection animals were deeply anesthetized with isofluorane and perfused transcardially with 0.9% NaCl solution. The gastrocnemius muscle and Hippocampus were quickly removed, frozen on dry ice and stored at −80 °C for RNA isolation and microarray analysis.
 
Contributor(s) Kobilo T, Zhang Y, Guerrieri D, Collica S, Becker KG, van Praag H
Citation(s) 24443745
Submission date Sep 13, 2013
Last update date Jun 22, 2020
Contact name Supriyo De
Organization name NIA-IRP, NIH
Department Laboratory of Genetics and Genomics
Lab Computational Biology & Genomics Core
Street address 251 Bayview Blvd
City Baltimore
State/province Maryland
ZIP/Postal code 21224
Country USA
 
Platforms (1)
GPL6885 Illumina MouseRef-8 v2.0 expression beadchip
Samples (32)
GSM1231436 Hippocampus_AICAR-14days_Replicate-1
GSM1231437 Hippocampus_AICAR-14days_Replicate-2
GSM1231438 Hippocampus_AICAR-14days_Replicate-3
Relations
BioProject PRJNA219209

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE50873_RAW.tar 3.1 Mb (http)(custom) TAR
GSE50873_non-normalized.txt.gz 3.2 Mb (ftp)(http) TXT
Raw data are available on Series record
Processed data included within Sample table

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