PMID- 24120943
OWN - NLM
STAT- MEDLINE
DCOM- 20140605
LR  - 20231213
IS  - 1932-7420 (Electronic)
IS  - 1550-4131 (Print)
IS  - 1550-4131 (Linking)
VI  - 18
IP  - 5
DP  - 2013 Nov 5
TI  - Exercise induces hippocampal BDNF through a PGC-1alpha/FNDC5 pathway.
PG  - 649-59
LID - S1550-4131(13)00377-X [pii]
LID - 10.1016/j.cmet.2013.09.008 [doi]
AB  - Exercise can improve cognitive function and has been linked to the increased 
      expression of brain-derived neurotrophic factor (BDNF). However, the underlying 
      molecular mechanisms driving the elevation of this neurotrophin remain unknown. 
      Here we show that FNDC5, a previously identified muscle protein that is induced 
      in exercise and is cleaved and secreted as irisin, is also elevated by endurance 
      exercise in the hippocampus of mice. Neuronal Fndc5 gene expression is regulated 
      by PGC-1alpha, and Pgc1a(-/-) mice show reduced Fndc5 expression in the brain. Forced 
      expression of FNDC5 in primary cortical neurons increases Bdnf expression, 
      whereas RNAi-mediated knockdown of FNDC5 reduces Bdnf. Importantly, peripheral 
      delivery of FNDC5 to the liver via adenoviral vectors, resulting in elevated 
      blood irisin, induces expression of Bdnf and other neuroprotective genes in the 
      hippocampus. Taken together, our findings link endurance exercise and the 
      important metabolic mediators, PGC-1alpha and FNDC5, with BDNF expression in the 
      brain.
CI  - Copyright (c) 2013 Elsevier Inc. All rights reserved.
FAU - Wrann, Christiane D
AU  - Wrann CD
AD  - Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical 
      School, 44 Binney Street, Boston, MA 02115, USA.
FAU - White, James P
AU  - White JP
FAU - Salogiannnis, John
AU  - Salogiannnis J
FAU - Laznik-Bogoslavski, Dina
AU  - Laznik-Bogoslavski D
FAU - Wu, Jun
AU  - Wu J
FAU - Ma, Di
AU  - Ma D
FAU - Lin, Jiandie D
AU  - Lin JD
FAU - Greenberg, Michael E
AU  - Greenberg ME
FAU - Spiegelman, Bruce M
AU  - Spiegelman BM
LA  - eng
GR  - DK90861/DK/NIDDK NIH HHS/United States
GR  - DK31405/DK/NIDDK NIH HHS/United States
GR  - R37 DK031405/DK/NIDDK NIH HHS/United States
GR  - RC4 DK090861/DK/NIDDK NIH HHS/United States
GR  - R01 DK054477/DK/NIDDK NIH HHS/United States
GR  - R01 DK031405/DK/NIDDK NIH HHS/United States
GR  - P30 DK020572/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20131010
PL  - United States
TA  - Cell Metab
JT  - Cell metabolism
JID - 101233170
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (FNDC5 protein, mouse)
RN  - 0 (Fibronectins)
RN  - 0 (Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha)
RN  - 0 (Ppargc1a protein, mouse)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Transcription Factors)
SB  - IM
CIN - Cell Metab. 2013 Nov 5;18(5):612-4. PMID: 24206660
MH  - Adenoviridae/genetics
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Feedback, Physiological/drug effects
MH  - Fibronectins/genetics/*metabolism
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Developmental/drug effects
MH  - Genetic Vectors/metabolism
MH  - Hippocampus/drug effects/*metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/drug effects/metabolism
MH  - Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
MH  - *Physical Conditioning, Animal
MH  - Protein Binding/drug effects
MH  - Receptors, Estrogen/metabolism
MH  - Recombinant Proteins/pharmacology
MH  - *Signal Transduction/drug effects/genetics
MH  - Transcription Factors/*metabolism
MH  - ERRalpha Estrogen-Related Receptor
PMC - PMC3980968
MID - NIHMS524991
EDAT- 2013/10/15 06:00
MHDA- 2014/06/06 06:00
PMCR- 2014/11/05
CRDT- 2013/10/15 06:00
PHST- 2013/06/20 00:00 [received]
PHST- 2013/08/13 00:00 [revised]
PHST- 2013/09/06 00:00 [accepted]
PHST- 2013/10/15 06:00 [entrez]
PHST- 2013/10/15 06:00 [pubmed]
PHST- 2014/06/06 06:00 [medline]
PHST- 2014/11/05 00:00 [pmc-release]
AID - S1550-4131(13)00377-X [pii]
AID - 10.1016/j.cmet.2013.09.008 [doi]
PST - ppublish
SO  - Cell Metab. 2013 Nov 5;18(5):649-59. doi: 10.1016/j.cmet.2013.09.008. Epub 2013 
      Oct 10.