PMID- 18160634 OWN - NLM STAT- MEDLINE DCOM- 20080205 LR - 20200225 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 27 IP - 52 DP - 2007 Dec 26 TI - Selective deletion of Bdnf in the ventromedial and dorsomedial hypothalamus of adult mice results in hyperphagic behavior and obesity. PG - 14265-74 AB - Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are expressed in several hypothalamic and hindbrain nuclei involved in regulating energy homeostasis, developmentally and in the adult animal. Their depletion during the fetal or early postnatal periods when developmental processes are still ongoing elicits hyperphagic behavior and obesity in mice. Whether BDNF is a chief element in appetite control in the mature brain remains controversial. The required sources of this neurotrophin are also unknown. We show that glucose administration rapidly induced BDNF mRNA expression, mediated by Bdnf promoter 1, and TrkB transcription in the ventromedial hypothalamus (VMH) of adult mice, consistent with a role of this pathway in satiety. Using viral-mediated selective knock-down of BDNF in the VMH and dorsomedial hypothalamus (DMH) of adult mice, we were able to elucidate the physiological relevance of BDNF in energy balance regulation. Site-specific mutants exhibited hyperphagic behavior and obesity but normal energy expenditure. Furthermore, intracerebroventricular administration of BDNF triggered an immediate neuronal response in multiple hypothalamic nuclei in wild-type mice, suggesting that its anorexigenic actions involve short-term mechanisms. Locomotor, aggressive, and depressive-like behaviors, all of which are associated with neural circuits involving the VMH, were not altered in VMH/DMH-specific BDNF mutants. These findings demonstrate that BDNF is an integral component of central mechanisms mediating satiety in the adult mouse and, moreover, that its synthesis in the VMH and/or DMH is required for the suppression of appetite. FAU - Unger, Thaddeus J AU - Unger TJ AD - Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA. FAU - Calderon, German A AU - Calderon GA FAU - Bradley, Leila C AU - Bradley LC FAU - Sena-Esteves, Miguel AU - Sena-Esteves M FAU - Rios, Maribel AU - Rios M LA - eng GR - DK073311/DK/NIDDK NIH HHS/United States GR - MH67817/MH/NIMH NIH HHS/United States GR - P30 DK34928/DK/NIDDK NIH HHS/United States GR - P30 NS047243/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 147336-22-9 (Green Fluorescent Proteins) RN - EC 2.7.10.1 (Receptor, trkB) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Behavior, Animal MH - Body Weight/genetics MH - Brain-Derived Neurotrophic Factor/*deficiency MH - Feeding Behavior/physiology MH - *Gene Deletion MH - Gene Expression Regulation/drug effects MH - Genetic Vectors/physiology MH - Glucose/pharmacology MH - Green Fluorescent Proteins/genetics/metabolism MH - Hyperglycemia/genetics MH - Hyperinsulinism/genetics MH - Hyperlipidemias/genetics MH - Hyperphagia/*genetics MH - Hypothalamus, Middle/drug effects/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Obesity/*genetics/*pathology MH - Proto-Oncogene Proteins c-fos/metabolism MH - Receptor, trkB/genetics/metabolism MH - Time Factors PMC - PMC6673437 EDAT- 2007/12/28 09:00 MHDA- 2008/02/06 09:00 PMCR- 2008/06/26 CRDT- 2007/12/28 09:00 PHST- 2007/12/28 09:00 [pubmed] PHST- 2008/02/06 09:00 [medline] PHST- 2007/12/28 09:00 [entrez] PHST- 2008/06/26 00:00 [pmc-release] AID - 27/52/14265 [pii] AID - 3299376 [pii] AID - 10.1523/JNEUROSCI.3308-07.2007 [doi] PST - ppublish SO - J Neurosci. 2007 Dec 26;27(52):14265-74. doi: 10.1523/JNEUROSCI.3308-07.2007.