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Title: High motivation for exercise is associated with altered chromatin regulators of monoamine receptor gene expression in the striatum of selectively bred mice      
keywords:
Transcriptome or Gene expression
ID:
PRJNA340182
description:
Though exercise is critical for health and wellbeing, many lack the motivation to exercise, and it is unclear how motivation might be increased. To uncover the molecular underpinnings of increased motivation for exercise, we analyzed the transcriptome of the striatum in four mouse lines selectively bred for high voluntary wheel running and four non-selected control lines. The striatum was dissected and RNA was extracted and sequenced from four individuals of each strain. We found multiple genes and gene systems with strong relationships to both selection and running history over the previous 6 days. Among these genes were Htr1b, a serotonin receptor subunit, and Slc38a2, a marker for both glutamatergic and GABAergic signaling. Systems analysis of the raw results found enrichment of transcriptional regulation and kinase genes. Further, we identified a splice variant affecting the Wnt related Golgi signaling gene Tmed5. Using coexpression network analysis, we found a cluster of interrelated coexpression modules with relationships to running behavior. From these modules, we built a network correlated with running that predicts a mechanistic relationship between transcriptional regulation by nucleosome structure, a system implicated in our previous work, and Htr1b expression, implicated in the present work. Using the Library of Integrated Cellular Signals, we found that the tyrosine kinase inhibitor Linifanib and the delta-opioid receptor antagonist 7-benzylidenenaltrexone (BNTX) produced similar patterns of gene expression in multiple cell lines as we observed in the striatum of the high-runner lines. Hence, these two drugs are predicted to increase motivation for exercise. Taken together, our findings support a neurobiological framework of exercise motivation where chromatin state leads to differences in dopamine signaling through modulation of both the primary neurotransmitters glutamate and GABA, and by neuromodulators such as serotonin. Overall design: Total RNA samples from a total of 31 biological replicates (striatum samples from individual mice) were sequenced: 15 biological replicates from the four replicate randomly-bred control lines (control) and 16 samples from the replicate lines selected for high voluntary wheel running (selected). Each line included 4 biological replicates except Line 1 (L1), which only had 3 biological replicates.
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landingpage: http://www.ncbi.nlm.nih.gov/bioproject/PRJNA340182
authentication:
none
authorization:
none
ID:
pmid:27749013
name:
Mus musculus domesticus
ncbiID:
ncbitax:10092
abbreviation:
NCBI
homePage: http://www.ncbi.nlm.nih.gov
ID:
SCR:006472
name:
National Center for Biotechnology Information
homePage: http://www.ncbi.nlm.nih.gov/bioproject
ID:
SCR:004801
name:
NCBI BioProject