PMID- 26042201
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20150604
LR  - 20181113
IS  - 2212-8778 (Print)
IS  - 2212-8778 (Electronic)
IS  - 2212-8778 (Linking)
VI  - 4
IP  - 6
DP  - 2015 Jun
TI  - Brain-derived neurotrophic factor is required for axonal growth of selective 
      groups of neurons in the arcuate nucleus.
PG  - 471-82
LID - 10.1016/j.molmet.2015.03.003 [doi]
AB  - OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is a potent regulator of 
      neuronal development, and the Bdnf gene produces two populations of transcripts 
      with either a short or long 3' untranslated region (3' UTR). Deficiencies in BDNF 
      signaling have been shown to cause severe obesity in humans; however, it remains 
      unknown how BDNF signaling impacts the organization of neuronal circuits that 
      control energy balance. METHODS: We examined the role of BDNF on survival, axonal 
      projections, and synaptic inputs of neurons in the arcuate nucleus (ARH), a 
      structure critical for the control of energy balance, using Bdnf (klox/klox) 
      mice, which lack long 3' UTR Bdnf mRNA and develop severe hyperphagic obesity. 
      RESULTS: We found that a small fraction of neurons that express the receptor for 
      BDNF, TrkB, also expressed proopiomelanocortin (POMC) or neuropeptide Y 
      (NPY)/agouti-related protein (AgRP) in the ARH. Bdnf(klox/klox) mice had normal 
      numbers of POMC, NPY, and TrkB neurons in the ARH; however, retrograde labeling 
      revealed a drastic reduction in the number of ARH axons that project to the 
      paraventricular hypothalamus (PVH) in these mice. In addition, fewer POMC and 
      AgRP axons were found in the dorsomedial hypothalamic nucleus (DMH) and the 
      lateral part of PVH, respectively, in Bdnf (klox/klox) mice. Using 
      immunohistochemistry, we examined the impact of BDNF deficiency on inputs to ARH 
      neurons. We found that excitatory inputs onto POMC and NPY neurons were increased 
      and decreased, respectively, in Bdnf (klox/klox) mice, likely due to a 
      compensatory response to marked hyperphagia displayed by the mutant mice. 
      CONCLUSION: This study shows that the majority of TrkB neurons in the ARH are 
      distinct from known neuronal populations and that BDNF plays a critical role in 
      directing projections from these neurons to the DMH and PVH. We propose that 
      hyperphagic obesity due to BDNF deficiency is in part attributable to impaired 
      axonal growth of TrkB-expressing ARH neurons.
FAU - Liao, Guey-Ying
AU  - Liao GY
AD  - Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 
      33458, USA.
FAU - Bouyer, Karine
AU  - Bouyer K
AD  - The Saban Research Institute, Children's Hospital Los Angeles, University of 
      Southern California, Los Angeles, CA 90027, USA.
FAU - Kamitakahara, Anna
AU  - Kamitakahara A
AD  - The Saban Research Institute, Children's Hospital Los Angeles, University of 
      Southern California, Los Angeles, CA 90027, USA.
FAU - Sahibzada, Niaz
AU  - Sahibzada N
AD  - Department of Pharmacology and Physiology, Georgetown University Medical Center, 
      Washington, DC 20057, USA.
FAU - Wang, Chien-Hua
AU  - Wang CH
AD  - The Saban Research Institute, Children's Hospital Los Angeles, University of 
      Southern California, Los Angeles, CA 90027, USA.
FAU - Rutlin, Michael
AU  - Rutlin M
AD  - Solomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, 
      The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
FAU - Simerly, Richard B
AU  - Simerly RB
AD  - The Saban Research Institute, Children's Hospital Los Angeles, University of 
      Southern California, Los Angeles, CA 90027, USA.
FAU - Xu, Baoji
AU  - Xu B
AD  - Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 
      33458, USA.
LA  - eng
GR  - R01 DK089237/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20150320
PL  - Germany
TA  - Mol Metab
JT  - Molecular metabolism
JID - 101605730
PMC - PMC4443292
OTO - NOTNLM
OT  - 3' UTR, 3' untranslated region
OT  - ARH, arcuate nucleus of the hypothalamus
OT  - AgRP neuron
OT  - AgRP, agouti-related peptide
OT  - BDNF, brain-derived neurotrophic factor
OT  - DMH, dorsomedial nucleus of the hypothalamus
OT  - DiI, 1,1'-dioctadecyl-3, 3,3',3'-tetramethylindocarbocyanine perchlorate
OT  - Excitatory synapse
OT  - Inhibitory synapse
OT  - LHA, lateral hypothalamic area
OT  - NPY, neuropeptide Y
OT  - PBS, phosphate buffer saline
OT  - POMC neuron
OT  - POMC, proopiomelanocortin
OT  - PVH, paraventricular hypothalamic nucleus
OT  - PVHlp, lateral part of the PVH
OT  - PVHmp, medial parvicellular part of the PVH
OT  - PVHmpd, medial parvicellular part of the PVH
OT  - PVHpml, lateral magnocellular part of the PVH
OT  - PVHpv, periventricular part of the PVH
OT  - PVT, paraventricular nucleus of the thalamus
OT  - Paraventricular hypothalamus
OT  - TrkB
OT  - Vgat, vesicular GABA transporter
OT  - Vglut2, vesicular glutamate transporter 2
OT  - aBNST, anterior bed nucleus of the stria terminalis
OT  - pSTAT3, phosphorylated signal transducer and activator of transcription 3
OT  - alpha-MSH, alpha-melanocyte stimulating hormone
EDAT- 2015/06/05 06:00
MHDA- 2015/06/05 06:01
PMCR- 2015/03/20
CRDT- 2015/06/05 06:00
PHST- 2015/03/02 00:00 [received]
PHST- 2015/03/08 00:00 [revised]
PHST- 2015/03/11 00:00 [accepted]
PHST- 2015/06/05 06:00 [entrez]
PHST- 2015/06/05 06:00 [pubmed]
PHST- 2015/06/05 06:01 [medline]
PHST- 2015/03/20 00:00 [pmc-release]
AID - S2212-8778(15)00058-7 [pii]
AID - 10.1016/j.molmet.2015.03.003 [doi]
PST - epublish
SO  - Mol Metab. 2015 Mar 20;4(6):471-82. doi: 10.1016/j.molmet.2015.03.003. 
      eCollection 2015 Jun.