Physical activity-associated gene expression signature in nonhuman primate motor cortex.
It has been established that weight gain and weight loss are heavily influenced by activity level. In this study, we hypothesized that the motor cortex exhibits a distinct physical activity-associated gene expression profile, which may underlie changes in weight associated with movement. Using DNA microarrays we profiled gene expression in the motor cortex of a group of 14 female rhesus monkeys (Macaca mulatta) with a wide range of stable physical activity levels. We found that neuronal growth factor signaling and nutrient sensing transcripts in the brain were highly correlated with physical activity. A follow-up of AKT3 expression changes (a gene at the apex of neuronal survival and nutrient sensing) revealed increased protein levels of total AKT, phosphorylated AKT, and forkhead box O3 (FOXO3), one of AKT's main downstream effectors. In addition, we successfully validated three other genes via quantitative polymerase chain reaction (qPCR) (cereblon (CRBN), origin recognition complex subunit 4-like, and pyruvate dehydrogenase 4 (PDK4)). We conclude that these genes are important in the physical activity-associated pathway in the motor cortex, and may be critical for physical activity-associated changes in body weight and neuroprotection.
Department of Psychiatry Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee, USA.
Amanda C
AC
Mitchell
Rehana K
RK
Leak
Krassimira
K
Garbett
Michael J
MJ
Zigmond
Judy L
JL
Cameron
Károly
K
Mirnics
D000818:Animals; D005260:Female; D020869:Gene Expression Profiling; D008253:Macaca mulatta / Q000235:genetics; D009043:Motor Activity / Q000235:genetics*; D009044:Motor Cortex / Q000378:metabolism / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics
D051057:Proto-Oncogene Proteins c-akt