Document Detail


Activity-dependent, stress-responsive BDNF signaling and the quest for optimal brain health and resilience throughout the lifespan.
MedLine Citation:
PMID:  23079624     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
S M Rothman; M P Mattson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Review     Date:  2012-10-16
Journal Detail:
Title:  Neuroscience     Volume:  239     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-04-15     Completed Date:  2013-10-17     Revised Date:  2014-06-04    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  228-40     Citation Subset:  IM    
Copyright Information:
Published by Elsevier Ltd.
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MeSH Terms
Descriptor/Qualifier:
Animals
Brain / physiology*
Brain-Derived Neurotrophic Factor / metabolism*
Exercise / physiology*
Humans
Neuronal Plasticity / physiology
Signal Transduction
Stress, Physiological
Grant Support
ID/Acronym/Agency:
ZIA AG000312-10/AG/NIA NIH HHS; ZIA AG000312-11/AG/NIA NIH HHS; ZIA AG000314-10/AG/NIA NIH HHS; ZIA AG000314-11/AG/NIA NIH HHS; ZIA AG000315-11/AG/NIA NIH HHS; ZIA AG000315-12/AG/NIA NIH HHS; ZIA AG000317-11/AG/NIA NIH HHS; ZIA AG000317-12/AG/NIA NIH HHS; ZIA AG000330-04/AG/NIA NIH HHS; ZIA AG000331-04/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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