PMID- 23079624
OWN - NLM
STAT- MEDLINE
DCOM- 20131017
LR  - 20240410
IS  - 1873-7544 (Electronic)
IS  - 0306-4522 (Print)
IS  - 0306-4522 (Linking)
VI  - 239
DP  - 2013 Jun 3
TI  - Activity-dependent, stress-responsive BDNF signaling and the quest for optimal 
      brain health and resilience throughout the lifespan.
PG  - 228-40
LID - S0306-4522(12)01022-6 [pii]
LID - 10.1016/j.neuroscience.2012.10.014 [doi]
AB  - During development of the nervous system, the formation of connections (synapses) 
      between neurons is dependent upon electrical activity in those neurons, and 
      neurotrophic factors produced by target cells play a pivotal role in such 
      activity-dependent sculpting of the neural networks. A similar interplay between 
      neurotransmitter and neurotrophic factor signaling pathways mediates adaptive 
      responses of neural networks to environmental demands in adult mammals, with the 
      excitatory neurotransmitter glutamate and brain-derived neurotrophic factor 
      (BDNF) being particularly prominent regulators of synaptic plasticity throughout 
      the central nervous system. Optimal brain health throughout the lifespan is 
      promoted by intermittent challenges such as exercise, cognitive stimulation and 
      dietary energy restriction, that subject neurons to activity-related metabolic 
      stress. At the molecular level, such challenges to neurons result in the 
      production of proteins involved in neurogenesis, learning and memory and neuronal 
      survival; examples include proteins that regulate mitochondrial biogenesis, 
      protein quality control, and resistance of cells to oxidative, metabolic and 
      proteotoxic stress. BDNF signaling mediates up-regulation of several such 
      proteins including the protein chaperone GRP-78, antioxidant enzymes, the cell 
      survival protein Bcl-2, and the DNA repair enzyme APE1. Insufficient exposure to 
      such challenges, genetic factors may conspire to impair BDNF production and/or 
      signaling resulting in the vulnerability of the brain to injury and 
      neurodegenerative disorders including Alzheimer's, Parkinson's and Huntington's 
      diseases. Further, BDNF signaling is negatively regulated by glucocorticoids. 
      Glucocorticoids impair synaptic plasticity in the brain by negatively regulating 
      spine density, neurogenesis and long-term potentiation, effects that are 
      potentially linked to glucocorticoid regulation of BDNF. Findings suggest that 
      BDNF signaling in specific brain regions mediates some of the beneficial effects 
      of exercise and energy restriction on peripheral energy metabolism and the 
      cardiovascular system. Collectively, the findings described in this article 
      suggest the possibility of developing prescriptions for optimal brain health 
      based on activity-dependent BDNF signaling.
CI  - Published by Elsevier Ltd.
FAU - Rothman, S M
AU  - Rothman SM
AD  - Laboratory of Neurosciences, National Institute on Aging, Intramural Research 
      Program, National Institutes of Health, 251 Bayview Boulevard, Baltimore, MD 
      21224, USA. rothmansm@mail.nih.gov
FAU - Mattson, M P
AU  - Mattson MP
LA  - eng
GR  - ZIA AG000315/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000317/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000330-04/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000315-11/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000317-11/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000312/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000317-12/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000315-12/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000314-10/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000312-11/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000314-11/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000312-10/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000314/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000331-04/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Review
DEP - 20121016
PL  - United States
TA  - Neuroscience
JT  - Neuroscience
JID - 7605074
RN  - 0 (Brain-Derived Neurotrophic Factor)
SB  - IM
MH  - Animals
MH  - Brain/*physiology
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Exercise/*physiology
MH  - Humans
MH  - Neuronal Plasticity/physiology
MH  - Signal Transduction
MH  - Stress, Physiological
PMC - PMC3629379
MID - NIHMS415177
EDAT- 2012/10/20 06:00
MHDA- 2013/10/18 06:00
PMCR- 2014/06/03
CRDT- 2012/10/20 06:00
PHST- 2012/07/24 00:00 [received]
PHST- 2012/09/24 00:00 [revised]
PHST- 2012/10/05 00:00 [accepted]
PHST- 2012/10/20 06:00 [entrez]
PHST- 2012/10/20 06:00 [pubmed]
PHST- 2013/10/18 06:00 [medline]
PHST- 2014/06/03 00:00 [pmc-release]
AID - S0306-4522(12)01022-6 [pii]
AID - 10.1016/j.neuroscience.2012.10.014 [doi]
PST - ppublish
SO  - Neuroscience. 2013 Jun 3;239:228-40. doi: 10.1016/j.neuroscience.2012.10.014. 
      Epub 2012 Oct 16.