PMID- 30071007
OWN - NLM
STAT- MEDLINE
DCOM- 20190131
LR  - 20231104
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 8
DP  - 2018
TI  - Brain region-dependent gene networks associated with selective breeding for 
      increased voluntary wheel-running behavior.
PG  - e0201773
LID - 10.1371/journal.pone.0201773 [doi]
LID - e0201773
AB  - Mouse lines selectively bred for high voluntary wheel-running behavior are 
      helpful models for uncovering gene networks associated with increased motivation 
      for physical activity and other reward-dependent behaviors. The fact that 
      multiple brain regions are hypothesized to contribute to distinct behavior 
      components necessitates the simultaneous study of these regions. The goals of 
      this study were to identify brain-region dependent and independent gene 
      expression patterns, regulators, and networks associated with increased voluntary 
      wheel-running behavior. The cerebellum and striatum from a high voluntary running 
      line and a non-selected control line were compared. Neuropeptide genes annotated 
      to reward-dependent processes including neuropeptide S receptor 1 (Npsr1), 
      neuropeptide Y (Npy), and proprotein convertase subtilisin/kexin type 9 (Pcsk9), 
      and genes implicated in motor coordination including vitamin D receptor (Vdr) and 
      keratin, type I cytoskeletal 25 (Krt25) were among the genes exhibiting activity 
      line-by-region interaction effects. Genes annotated to the Parkinson pathway 
      presented consistent line patterns, albeit at different orders of magnitude 
      between brain regions, suggesting some parallel events in response to selection 
      for high voluntary activity. The comparison of gene networks between brain 
      regions highlighted genes including transcription factor AP-2-delta (Tfap2d), 
      distal-less homeobox 5 gene (Dlx5) and sine oculis homeobox homolog 3 (Six3) that 
      exhibited line differential expression in one brain region and are associated 
      with reward-dependent behaviors. Transcription factors including En2, Stat6 and 
      Eomes predominated among regulators of genes that differed in expression between 
      lines. Results from the simultaneous study of striatum and cerebellum confirm the 
      necessity to study molecular mechanisms associated with voluntary activity and 
      reward-dependent behaviors in consideration of brain region dependencies.
FAU - Zhang, Pan
AU  - Zhang P
AD  - Illinois Informatics Institute, University of Illinois at Urbana-Champaign, 
      Urbana, IL, United States of America.
AD  - Department of Animal Sciences, University of Illinois at Urbana-Champaign, 
      Urbana, IL, United States of America.
FAU - Rhodes, Justin S
AU  - Rhodes JS
AD  - Beckman Institute for Advanced Science and Technology, Urbana, IL, United States 
      of America.
AD  - Center for Nutrition, Learning and Memory, University of Illinois at 
      Urbana-Champaign, Urbana, IL, United States of America.
FAU - Garland, Theodore Jr
AU  - Garland T Jr
AUID- ORCID: 0000-0002-7916-3552
AD  - Department of Evolution, Ecology, and Organismal Biology, University of 
      California, Riverside, CA, United States of America.
FAU - Perez, Sam D
AU  - Perez SD
AD  - Beckman Institute for Advanced Science and Technology, Urbana, IL, United States 
      of America.
FAU - Southey, Bruce R
AU  - Southey BR
AD  - Department of Animal Sciences, University of Illinois at Urbana-Champaign, 
      Urbana, IL, United States of America.
FAU - Rodriguez-Zas, Sandra L
AU  - Rodriguez-Zas SL
AUID- ORCID: 0000-0003-1122-4758
AD  - Department of Animal Sciences, University of Illinois at Urbana-Champaign, 
      Urbana, IL, United States of America.
AD  - Department of Statistics, University of Illinois at Urbana-Champaign, Urbana, IL, 
      United States of America.
AD  - Carle Woese Institute for Genomic Biology, University of Illinois at 
      Urbana-Champaign, Urbana, IL, United States of America.
LA  - eng
GR  - P30 DA018310/DA/NIDA NIH HHS/United States
GR  - R21 MH096030/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20180802
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
SB  - IM
MH  - Animals
MH  - Behavior, Addictive/genetics/metabolism
MH  - Cerebellum/*metabolism
MH  - Corpus Striatum/*metabolism
MH  - Gene Expression
MH  - *Gene Regulatory Networks
MH  - Male
MH  - Mice, Inbred Strains
MH  - Reward
MH  - Running/*physiology/psychology
MH  - *Selective Breeding
MH  - Species Specificity
MH  - *Transcriptome/genetics/physiology
MH  - Volition
PMC - PMC6072066
COIS- The authors have declared that no competing interests exist.
EDAT- 2018/08/03 06:00
MHDA- 2019/02/01 06:00
PMCR- 2018/08/02
CRDT- 2018/08/03 06:00
PHST- 2018/05/04 00:00 [received]
PHST- 2018/07/20 00:00 [accepted]
PHST- 2018/08/03 06:00 [entrez]
PHST- 2018/08/03 06:00 [pubmed]
PHST- 2019/02/01 06:00 [medline]
PHST- 2018/08/02 00:00 [pmc-release]
AID - PONE-D-18-13486 [pii]
AID - 10.1371/journal.pone.0201773 [doi]
PST - epublish
SO  - PLoS One. 2018 Aug 2;13(8):e0201773. doi: 10.1371/journal.pone.0201773. 
      eCollection 2018.