Document Detail

Long-term infusion of brain-derived neurotrophic factor reduces food intake and body weight via a corticotrophin-releasing hormone pathway in the paraventricular nucleus of the hypothalamus.
MedLine Citation:
PMID:  20561155     Owner:  NLM     Status:  MEDLINE    
Brain-derived neurotrophic factor (BDNF) has been implicated in learning, depression and energy metabolism. However, the neuronal mechanisms underlying the effects of BDNF on energy metabolism remain unclear. The present study aimed to elucidate the neuronal pathways by which BDNF controls feeding behaviour and energy balance. Using an osmotic mini-pump, BDNF or control artificial cerebrospinal fluid was infused i.c.v. at the lateral ventricle or into the paraventricular nucleus of the hypothalamus (PVN) for 12 days. Intracerebroventricular BDNF up-regulated mRNA expression of corticotrophin-releasing hormone (CRH) and urocortin in the PVN. TrkB, the receptor for BDNF, was expressed in the PVN neurones, including those containing CRH. Both i.c.v. and intra-PVN-administered BDNF decreased food intake and body weight. These effects of BDNF on food intake and body weight were counteracted by the co-administration of alpha-helical-CRH, an antagonist for the CRH and urocortin receptors CRH-R1/R2, and partly attenuated by a selective antagonist for CRH-R2 but not CRH-R1. Intracerebroventricular BDNF also decreased the subcutaneous and visceral fat mass, adipocyte size and serum triglyceride levels, which were all attenuated by alpha-helical-CRH. Furthermore, BDNF decreased the respiratory quotient and raised rectal temperature, which were counteracted by alpha-helical-CRH. These results indicate that the CRH-urocortin-CRH-R2 pathway in the PVN and connected areas mediates the long-term effects of BDNF to depress feeding and promote lipolysis.
M Toriya; F Maekawa; Y Maejima; T Onaka; K Fujiwara; T Nakagawa; M Nakata; T Yada
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-16
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  22     ISSN:  1365-2826     ISO Abbreviation:  J. Neuroendocrinol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-20     Completed Date:  2010-12-06     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  England    
Other Details:
Languages:  eng     Pagination:  987-95     Citation Subset:  IM    
Division of Integrative Physiology, Department of Physiology, Jichi Medical University, Shimostuke, Tochigi, Japan.
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MeSH Terms
Adipose Tissue / drug effects,  metabolism
Body Weight / drug effects*,  genetics
Brain-Derived Neurotrophic Factor / administration & dosage*,  pharmacology
Corticotropin-Releasing Hormone / administration & dosage,  genetics,  metabolism,  pharmacology,  physiology*
Down-Regulation / drug effects,  genetics
Drug Evaluation, Preclinical
Eating / drug effects*,  genetics
Infusions, Intraventricular
Paraventricular Hypothalamic Nucleus / drug effects*,  metabolism,  physiology
Peptide Fragments / administration & dosage,  pharmacology
Rats, Wistar
Signal Transduction / drug effects,  genetics,  physiology
Time Factors
Triglycerides / blood
Reg. No./Substance:
0/Brain-Derived Neurotrophic Factor; 0/Peptide Fragments; 0/Triglycerides; 9015-71-8/Corticotropin-Releasing Hormone; 96118-75-1/corticotropin releasing hormone (9-41)

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

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