PMID- 19179431
OWN - NLM
STAT- MEDLINE
DCOM- 20090618
LR  - 20091119
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 150
IP  - 6
DP  - 2009 Jun
TI  - Brain-derived neurotrophic factor/tropomyosin-related kinase receptor type B 
      signaling is a downstream effector of the brainstem melanocortin system in food 
      intake control.
PG  - 2646-53
LID - 10.1210/en.2008-1184 [doi]
AB  - It has been shown that the neurotropin brain-derived neurotrophic factor (BDNF) 
      and its high-affinity receptor, tropomyosin-related kinase receptor type B 
      (TrkB), contribute to the central control of food intake. BDNF has previously 
      been implicated as a probable downstream effector of melanocortinergic signaling 
      within the ventromedial hypothalamus, and we have shown its implication as an 
      anorexigenic factor within the brainstem autonomic integrator of food intake 
      control, namely the dorsal vagal complex (DVC). In the brainstem, the 
      melanocortinergic signaling pathway is known to integrate phasic responses to 
      satiety signals, such as cholecystokinin. In this study, we explored the 
      interactions between melanocortin and BDNF/TrkB signaling within the DVC. First, 
      we tested the effect of a local pharmacological activation or inhibition of 
      melanocortin receptors type 3/4 (MC3/4R) on BDNF protein content in the DVC of 
      adult rats. We showed that fourth intracerebroventricular delivery of MC3/4R 
      agonist and antagonist increased and decreased the BDNF protein content within 
      the DVC, respectively. Second, we showed that the orexigenic effect of a 
      selective MC4R antagonist delivered fourth-icv can be blocked by a 
      coadministration of BDNF. We also tested the causal role of BDNF/TrkB signaling 
      in the anorexigenic effect of melanocortinergic signaling by using a recently 
      developed analog-sensitive kinase allele murine model (TrkB(F616A) mice) and 
      showed that the pharmacological blockade of TrkB abolished the anorexigenic 
      effect of a selective MC4R agonist and of cholecystokinin. Our results provide 
      strong evidence for a role of BDNF as a downstream effector of melanocortinergic 
      signaling pathway within the DVC.
FAU - Bariohay, Bruno
AU  - Bariohay B
AD  - Departement de Physiologie Neurovegetative, Centre de Recherche de Neurobiologie 
      et Neurophysiologie de Marseille, CRN2M, Universite Paul Cezanne, Marseille cedex 
      20, France. bruno.lebrun@univ-cezanne.fr
FAU - Roux, Julien
AU  - Roux J
FAU - Tardivel, Catherine
AU  - Tardivel C
FAU - Trouslard, Jerome
AU  - Trouslard J
FAU - Jean, Andre
AU  - Jean A
FAU - Lebrun, Bruno
AU  - Lebrun B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090129
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (HS014 cyclic peptide)
RN  - 0 (Melanocortins)
RN  - 0 (Peptides, Cyclic)
RN  - 0 (Receptor, Melanocortin, Type 3)
RN  - 0 (Receptor, Melanocortin, Type 4)
RN  - 0 
      (acetyl-norleucyl(4)-(aspartyl(5)-histidyl(6)-phenylalanyl(7)-arginyl(8)-tryptophyl(9)-lysyl(10))cyclo-alpha-MSH(4-10)amide)
RN  - 168482-23-3 (SHU 9119)
RN  - 581-05-5 (alpha-MSH)
RN  - 9002-79-3 (Melanocyte-Stimulating Hormones)
RN  - 9011-97-6 (Cholecystokinin)
RN  - EC 2.7.10.1 (Receptor, trkB)
SB  - IM
MH  - Animals
MH  - Appetite Regulation/drug effects/*physiology
MH  - Brain Stem/drug effects/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Cholecystokinin/administration & dosage/pharmacology
MH  - Injections, Intraventricular
MH  - Male
MH  - Melanocortins/*metabolism
MH  - Melanocyte-Stimulating Hormones/administration & dosage/pharmacology
MH  - Mice
MH  - Mice, Knockout
MH  - Models, Animal
MH  - Peptides, Cyclic/administration & dosage/pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptor, Melanocortin, Type 3/agonists/antagonists & inhibitors/metabolism
MH  - Receptor, Melanocortin, Type 4/agonists/antagonists & inhibitors/metabolism
MH  - Receptor, trkB/genetics/*metabolism
MH  - Signal Transduction/drug effects/*physiology
MH  - alpha-MSH/administration & dosage/analogs & derivatives/pharmacology
EDAT- 2009/01/31 09:00
MHDA- 2009/06/19 09:00
CRDT- 2009/01/31 09:00
PHST- 2009/01/31 09:00 [entrez]
PHST- 2009/01/31 09:00 [pubmed]
PHST- 2009/06/19 09:00 [medline]
AID - en.2008-1184 [pii]
AID - 10.1210/en.2008-1184 [doi]
PST - ppublish
SO  - Endocrinology. 2009 Jun;150(6):2646-53. doi: 10.1210/en.2008-1184. Epub 2009 Jan 
      29.