Evidence map›Paper›PMID 26042201›Full record

ArticleMolecular metabolism2015

Brain-derived neurotrophic factor is required for axonal growth of selective groups of neurons in the arcuate nucleus.

Guey-Ying Liao, Karine Bouyer, Anna Kamitakahara, Niaz Sahibzada, Chien-Hua Wang, Michael Rutlin, Richard B Simerly, Baoji Xu

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.

0numbers the graph read from it
0cells of the map it votes in
27citing papers in PubMed
2.0field-weighted citation impact, top 15% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

27 citing papers in PubMed, 43 citations in OpenAlex.

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  12. Metabolic homeostasis via BDNF and its receptors.Trends in endocrinology and metabolism: TEM · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 1 country.

Guey-Ying LiaoDepartment of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
Karine BouyerThe Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA.
Anna KamitakaharaThe Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA.
Niaz SahibzadaDepartment of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057, USA.
Chien-Hua WangThe Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA.
Michael RutlinSolomon H. Snyder Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Richard B SimerlyThe Saban Research Institute, Children's Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA.
Baoji XuDepartment of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
Children's Hospital of Los Angeles · USScripps Research Institute · USUniversity of Southern California · USGeorgetown University Medical Center · USJohns Hopkins University · US

Funding

Regulation of Energy Homeostasis by BDNFR01DK089237 · NIDDK · SCRIPPS FLORIDA · PI SIMERLY, RICHARD B, XU, BAOJI · 2011 to 2014
$2.1M
NIDDK NIH HHS R01 DK089237
6 · The paper itself

Abstract

objectiveBrain-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.

methodsWe 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.

resultsWe 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.

conclusionThis 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.

Indexed as

3′ UTR, 3′ untranslated regionaBNST, anterior bed nucleus of the stria terminalisAgRP, agouti-related peptideAgRP neuronARH, arcuate nucleus of the hypothalamusBDNF, brain-derived neurotrophic factorDiI, 1,1′-dioctadecyl-3, 3,3′,3′-tetramethylindocarbocyanine perchlorateDMH, dorsomedial nucleus of the hypothalamusExcitatory synapseInhibitory synapseLHA, lateral hypothalamic areaNPY, neuropeptide YParaventricular hypothalamusPBS, phosphate buffer salinePOMC neuronPOMC, proopiomelanocortinpSTAT3, phosphorylated signal transducer and activator of transcription 3PVHlp, lateral part of the PVHPVHmpd, medial parvicellular part of the PVHPVHmp, medial parvicellular part of the PVHPVH, paraventricular hypothalamic nucleusPVHpml, lateral magnocellular part of the PVHPVHpv, periventricular part of the PVHPVT, paraventricular nucleus of the thalamusTrkBVgat, vesicular GABA transporterVglut2, vesicular glutamate transporter 2α-MSH, alpha-melanocyte stimulating hormone

Identifiers

PMID26042201
PMCPMC4443292
OpenAlexW2029303080

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.