PMID- 23615664
OWN - NLM
STAT- MEDLINE
DCOM- 20140324
LR  - 20240323
IS  - 1740-634X (Electronic)
IS  - 0893-133X (Print)
IS  - 0893-133X (Linking)
VI  - 38
IP  - 10
DP  - 2013 Sep
TI  - Exercise and sodium butyrate transform a subthreshold learning event into 
      long-term memory via a brain-derived neurotrophic factor-dependent mechanism.
PG  - 2027-34
LID - 10.1038/npp.2013.104 [doi]
AB  - We demonstrate that exercise enables hippocampal-dependent learning in conditions 
      that are normally subthreshold for encoding and memory formation, and depends on 
      hippocampal induction of brain-derived neurotrophic factor (BDNF) as a key 
      mechanism. Using a weak training paradigm in an object location memory (OLM) 
      task, we show that sedentary mice are unable to discriminate 24 h later between 
      familiar and novel object locations. In contrast, 3 weeks of prior voluntary 
      exercise enables strong discrimination in the spatial memory task. Cognitive 
      benefits of exercise match those attained with post-training sodium butyrate 
      (NaB), a histone deacetylase (HDAC) inhibitor previously shown to enable 
      subthreshold learning. We demonstrate that the enabling effects of exercise and 
      NaB on subthreshold OLM learning are dependent on hippocampal BDNF upregulation, 
      and are blocked by hippocampal infusion of BDNF short-interfering RNA. Exercise 
      and NaB increased bdnf transcripts I and IV, and the increases were associated 
      with BDNF promoter acetylation on H4K8 but not H4K12. These data provide support 
      for the concept that exercise engages epigenetic control mechanisms and serves as 
      a natural stimulus that operates in part like NaB and potentially other HDAC 
      inhibitors, placing the brain into a state of readiness for plasticity.
FAU - Intlekofer, Karlie A
AU  - Intlekofer KA
AD  - Institute for Memory Impairments and Neurological Disorders, University of 
      California Irvine, Irvine, CA, USA.
FAU - Berchtold, Nicole C
AU  - Berchtold NC
FAU - Malvaez, Melissa
AU  - Malvaez M
FAU - Carlos, Anthony J
AU  - Carlos AJ
FAU - McQuown, Susan C
AU  - McQuown SC
FAU - Cunningham, Michael J
AU  - Cunningham MJ
FAU - Wood, Marcelo A
AU  - Wood MA
FAU - Cotman, Carl W
AU  - Cotman CW
LA  - eng
GR  - F31 DA029368/DA/NIDA NIH HHS/United States
GR  - AG34667/AG/NIA NIH HHS/United States
GR  - R01 MH081004/MH/NIMH NIH HHS/United States
GR  - R01 AG034667/AG/NIA NIH HHS/United States
GR  - P01 AG000538/AG/NIA NIH HHS/United States
GR  - T32AG9629/AG/NIA NIH HHS/United States
GR  - F31DA29368/DA/NIDA NIH HHS/United States
GR  - MH081004/MH/NIMH NIH HHS/United States
GR  - AG00538/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20130424
PL  - England
TA  - Neuropsychopharmacology
JT  - Neuropsychopharmacology : official publication of the American College of 
      Neuropsychopharmacology
JID - 8904907
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Histone Deacetylase Inhibitors)
RN  - 0 (RNA, Small Interfering)
RN  - 107-92-6 (Butyric Acid)
SB  - IM
MH  - Acetylation
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/drug effects/metabolism/*physiology
MH  - Butyric Acid/*pharmacology
MH  - Discrimination Learning/drug effects/*physiology
MH  - Hippocampus/drug effects/*metabolism
MH  - Histone Deacetylase Inhibitors/pharmacology
MH  - Male
MH  - Memory, Long-Term/drug effects/*physiology
MH  - Mice
MH  - Microinjections
MH  - Physical Conditioning, Animal/*physiology
MH  - Promoter Regions, Genetic
MH  - RNA, Small Interfering/administration & dosage/pharmacology
MH  - Up-Regulation
PMC - PMC3746687
EDAT- 2013/04/26 06:00
MHDA- 2014/03/25 06:00
PMCR- 2014/09/01
CRDT- 2013/04/26 06:00
PHST- 2013/03/05 00:00 [received]
PHST- 2013/04/12 00:00 [revised]
PHST- 2013/04/14 00:00 [accepted]
PHST- 2013/04/26 06:00 [entrez]
PHST- 2013/04/26 06:00 [pubmed]
PHST- 2014/03/25 06:00 [medline]
PHST- 2014/09/01 00:00 [pmc-release]
AID - npp2013104 [pii]
AID - 10.1038/npp.2013.104 [doi]
PST - ppublish
SO  - Neuropsychopharmacology. 2013 Sep;38(10):2027-34. doi: 10.1038/npp.2013.104. Epub 
      2013 Apr 24.